id
stringlengths 14
28
| title
stringclasses 18
values | content
stringlengths 2
999
| contents
stringlengths 19
1.02k
|
|---|---|---|---|
Surgery_Schwartz_4002 | Surgery_Schwartz | If negative margins are not obtainable with reexcision, mastectomy is required. SLN is performed before removal of the primary breast tumor. When indicated, intraoperative assessment of the sentinel node can proceed while the segmental mastectomy is being performed.The use of oncoplastic surgery can be entertained at the time of segmental mastectomy or at a later time to improve the overall aesthetic outcome. The use of oncoplastic techniques range from a simple reshaping of breast tissue to local tissue rearrangement to the use of pedicled flaps or breast reduction techniques. The overall goal is to achieve the best possible aes-thetic result. In determining which patients are candidates for oncoplastic breast surgery, several factors should be considered, including the extent of the resection of breast tissue necessary to achieve negative margins, the location of the primary tumor within the breast, and the size of the patient’s breast and body habitus. Oncoplastic techniques are of | Surgery_Schwartz. If negative margins are not obtainable with reexcision, mastectomy is required. SLN is performed before removal of the primary breast tumor. When indicated, intraoperative assessment of the sentinel node can proceed while the segmental mastectomy is being performed.The use of oncoplastic surgery can be entertained at the time of segmental mastectomy or at a later time to improve the overall aesthetic outcome. The use of oncoplastic techniques range from a simple reshaping of breast tissue to local tissue rearrangement to the use of pedicled flaps or breast reduction techniques. The overall goal is to achieve the best possible aes-thetic result. In determining which patients are candidates for oncoplastic breast surgery, several factors should be considered, including the extent of the resection of breast tissue necessary to achieve negative margins, the location of the primary tumor within the breast, and the size of the patient’s breast and body habitus. Oncoplastic techniques are of |
Surgery_Schwartz_4003 | Surgery_Schwartz | of breast tissue necessary to achieve negative margins, the location of the primary tumor within the breast, and the size of the patient’s breast and body habitus. Oncoplastic techniques are of prime consideration when (a) a significant area of breast skin will need to be resected with the specimen to achieve negative margins; (b) a large vol-ume of breast parenchyma will be resected resulting in a signifi-cant defect; (c) the tumor is located between the nipple and the inframammary fold, an area often associated with unfavorable cosmetic outcomes; or (d) excision of the tumor and closure of the breast may result in malpositioning of the nipple.Mastectomy and Axillary DissectionA skin-sparing mastectomy removes all breast tissue, the nipple-areola complex, and scars from any prior biopsy pro-cedures.293,294 There is a recurrence rate of less than 6% to 8%, comparable to the long-term recurrence rates reported with stan-dard mastectomy, when skin-sparing mastectomy is used for patients | Surgery_Schwartz. of breast tissue necessary to achieve negative margins, the location of the primary tumor within the breast, and the size of the patient’s breast and body habitus. Oncoplastic techniques are of prime consideration when (a) a significant area of breast skin will need to be resected with the specimen to achieve negative margins; (b) a large vol-ume of breast parenchyma will be resected resulting in a signifi-cant defect; (c) the tumor is located between the nipple and the inframammary fold, an area often associated with unfavorable cosmetic outcomes; or (d) excision of the tumor and closure of the breast may result in malpositioning of the nipple.Mastectomy and Axillary DissectionA skin-sparing mastectomy removes all breast tissue, the nipple-areola complex, and scars from any prior biopsy pro-cedures.293,294 There is a recurrence rate of less than 6% to 8%, comparable to the long-term recurrence rates reported with stan-dard mastectomy, when skin-sparing mastectomy is used for patients |
Surgery_Schwartz_4004 | Surgery_Schwartz | There is a recurrence rate of less than 6% to 8%, comparable to the long-term recurrence rates reported with stan-dard mastectomy, when skin-sparing mastectomy is used for patients with Tis to T3 cancers. A total (simple) mastectomy without skin sparing removes all breast tissue, the nipple-areola complex, and skin. An extended simple mastectomy removes all breast tissue, the nipple-areola complex, skin, and the level I axillary lymph nodes. A modified radical (“Patey”) mastectomy removes all breast tissue, the nipple-areola complex, skin, and the levels I, II, and III axillary lymph nodes; the pectoralis minor that was divided and removed by Patey may be simply divided, giving improved access to level III nodes, and then left in situ, or occasionally the axillary clearance can be performed with-out dividing pectoralis minor. The Halsted radical mastectomy removes all breast tissue and skin, the nipple-areola complex, the pectoralis major and pectoralis minor muscles, and the levels | Surgery_Schwartz. There is a recurrence rate of less than 6% to 8%, comparable to the long-term recurrence rates reported with stan-dard mastectomy, when skin-sparing mastectomy is used for patients with Tis to T3 cancers. A total (simple) mastectomy without skin sparing removes all breast tissue, the nipple-areola complex, and skin. An extended simple mastectomy removes all breast tissue, the nipple-areola complex, skin, and the level I axillary lymph nodes. A modified radical (“Patey”) mastectomy removes all breast tissue, the nipple-areola complex, skin, and the levels I, II, and III axillary lymph nodes; the pectoralis minor that was divided and removed by Patey may be simply divided, giving improved access to level III nodes, and then left in situ, or occasionally the axillary clearance can be performed with-out dividing pectoralis minor. The Halsted radical mastectomy removes all breast tissue and skin, the nipple-areola complex, the pectoralis major and pectoralis minor muscles, and the levels |
Surgery_Schwartz_4005 | Surgery_Schwartz | with-out dividing pectoralis minor. The Halsted radical mastectomy removes all breast tissue and skin, the nipple-areola complex, the pectoralis major and pectoralis minor muscles, and the levels I, II, and III axillary lymph nodes. The use of systemic che-motherapy and hormonal therapy as well as adjuvant radiation therapy for breast cancer have nearly eliminated the need for the radical mastectomy.Nipple-areolar sparing mastectomy has been popularized over the last decade especially for risk-reducing mastectomy in high risk women. For those patients with a cancer diagno-sis, many consider the following factors for eligibility: tumor located more than 2 to 3 cm from the border of the areola, smaller breast size, minimal ptosis, no prior breast surgeries with periareolar incisions, body mass index less than 40 kg/m2, no active tobacco use, no prior breast irradiation, and no evi-dence of collagen vascular disease.For a variety of biologic, economic, and psychosocial rea-sons, some | Surgery_Schwartz. with-out dividing pectoralis minor. The Halsted radical mastectomy removes all breast tissue and skin, the nipple-areola complex, the pectoralis major and pectoralis minor muscles, and the levels I, II, and III axillary lymph nodes. The use of systemic che-motherapy and hormonal therapy as well as adjuvant radiation therapy for breast cancer have nearly eliminated the need for the radical mastectomy.Nipple-areolar sparing mastectomy has been popularized over the last decade especially for risk-reducing mastectomy in high risk women. For those patients with a cancer diagno-sis, many consider the following factors for eligibility: tumor located more than 2 to 3 cm from the border of the areola, smaller breast size, minimal ptosis, no prior breast surgeries with periareolar incisions, body mass index less than 40 kg/m2, no active tobacco use, no prior breast irradiation, and no evi-dence of collagen vascular disease.For a variety of biologic, economic, and psychosocial rea-sons, some |
Surgery_Schwartz_4006 | Surgery_Schwartz | mass index less than 40 kg/m2, no active tobacco use, no prior breast irradiation, and no evi-dence of collagen vascular disease.For a variety of biologic, economic, and psychosocial rea-sons, some women desire mastectomy rather than breast con-servation. Women who are less concerned about cosmesis may view mastectomy as the most expeditious and desirable thera-peutic option because it avoids the cost and inconvenience of radiation therapy. Some women whose primary breast cancers cannot be excised with a reasonable cosmetic result or those who have extensive microcalcifications are best treated with Brunicardi_Ch17_p0541-p0612.indd 59101/03/19 5:05 PM 592SPECIFIC CONSIDERATIONSPART IImastectomy. Similarly, women with large cancers that occupy the subareolar and central portions of the breast and women with multicentric primary cancers also undergo mastectomy.Modified Radical MastectomyA modified radical mastectomy preserves the pectoralis major muscle with removal of levels I, II, | Surgery_Schwartz. mass index less than 40 kg/m2, no active tobacco use, no prior breast irradiation, and no evi-dence of collagen vascular disease.For a variety of biologic, economic, and psychosocial rea-sons, some women desire mastectomy rather than breast con-servation. Women who are less concerned about cosmesis may view mastectomy as the most expeditious and desirable thera-peutic option because it avoids the cost and inconvenience of radiation therapy. Some women whose primary breast cancers cannot be excised with a reasonable cosmetic result or those who have extensive microcalcifications are best treated with Brunicardi_Ch17_p0541-p0612.indd 59101/03/19 5:05 PM 592SPECIFIC CONSIDERATIONSPART IImastectomy. Similarly, women with large cancers that occupy the subareolar and central portions of the breast and women with multicentric primary cancers also undergo mastectomy.Modified Radical MastectomyA modified radical mastectomy preserves the pectoralis major muscle with removal of levels I, II, |
Surgery_Schwartz_4007 | Surgery_Schwartz | breast and women with multicentric primary cancers also undergo mastectomy.Modified Radical MastectomyA modified radical mastectomy preserves the pectoralis major muscle with removal of levels I, II, and III (apical) axillary lymph nodes.293 The operation was first described by David Patey, a surgeon at St Bartholomew’s Hospital London, who reported a series of cases where he had removed the pectoralis minor muscle allowing complete dissection of the level III axil-lary lymph nodes while preserving the pectoralis major and the lateral pectoral nerve. A modified radical mastectomy permits preservation of the medial (anterior thoracic) pectoral nerve, which courses in the lateral neurovascular bundle of the axilla and usually penetrates the pectoralis minor to supply the lateral border of the pectoralis major. Anatomic boundaries of the mod-ified radical mastectomy are the anterior margin of the latissi-mus dorsi muscle laterally, the midline of the sternum medially, the subclavius | Surgery_Schwartz. breast and women with multicentric primary cancers also undergo mastectomy.Modified Radical MastectomyA modified radical mastectomy preserves the pectoralis major muscle with removal of levels I, II, and III (apical) axillary lymph nodes.293 The operation was first described by David Patey, a surgeon at St Bartholomew’s Hospital London, who reported a series of cases where he had removed the pectoralis minor muscle allowing complete dissection of the level III axil-lary lymph nodes while preserving the pectoralis major and the lateral pectoral nerve. A modified radical mastectomy permits preservation of the medial (anterior thoracic) pectoral nerve, which courses in the lateral neurovascular bundle of the axilla and usually penetrates the pectoralis minor to supply the lateral border of the pectoralis major. Anatomic boundaries of the mod-ified radical mastectomy are the anterior margin of the latissi-mus dorsi muscle laterally, the midline of the sternum medially, the subclavius |
Surgery_Schwartz_4008 | Surgery_Schwartz | of the pectoralis major. Anatomic boundaries of the mod-ified radical mastectomy are the anterior margin of the latissi-mus dorsi muscle laterally, the midline of the sternum medially, the subclavius muscle superiorly, and the caudal extension of the breast 2 to 3 cm inferior to the inframammary fold inferiorly. Skin-flap thickness varies with body habitus but ideally is 7 to 8 mm inclusive of skin and telasubcutanea (Fig. 17-35). Once the skin flaps are fully developed, the fascia of the pectoralis major muscle and the overlying breast tissue are elevated off the underlying musculature, which allows for the complete removal of the breast (Fig. 17-36).Subsequently, an axillary lymph node dissection is per-formed. The most lateral extent of the axillary vein is identified, and the areolar tissue of the lateral axillary space is elevated as the vein is cleared on its anterior and inferior surfaces. The areo-lar tissues at the junction of the axillary vein and the anterior edge of the | Surgery_Schwartz. of the pectoralis major. Anatomic boundaries of the mod-ified radical mastectomy are the anterior margin of the latissi-mus dorsi muscle laterally, the midline of the sternum medially, the subclavius muscle superiorly, and the caudal extension of the breast 2 to 3 cm inferior to the inframammary fold inferiorly. Skin-flap thickness varies with body habitus but ideally is 7 to 8 mm inclusive of skin and telasubcutanea (Fig. 17-35). Once the skin flaps are fully developed, the fascia of the pectoralis major muscle and the overlying breast tissue are elevated off the underlying musculature, which allows for the complete removal of the breast (Fig. 17-36).Subsequently, an axillary lymph node dissection is per-formed. The most lateral extent of the axillary vein is identified, and the areolar tissue of the lateral axillary space is elevated as the vein is cleared on its anterior and inferior surfaces. The areo-lar tissues at the junction of the axillary vein and the anterior edge of the |
Surgery_Schwartz_4009 | Surgery_Schwartz | tissue of the lateral axillary space is elevated as the vein is cleared on its anterior and inferior surfaces. The areo-lar tissues at the junction of the axillary vein and the anterior edge of the latissimus dorsi muscle, which include the lateral and subscapular lymph node groups (level I), are cleared. Care is taken to preserve the thoracodorsal neurovascular bundle. The dissection then continues medially with clearance of the central axillary lymph node group (level II). The long thoracic nerve of Bell is identified and preserved as it travels in the investing fascia of the serratus anterior muscle. Every effort is made to preserve this nerve because permanent disability with a winged scapula and shoulder weakness will follow denervation of the serratus anterior muscle. Patey divided the pectoralis minor and removed it to allow access right up to the apex of the axilla. The pectoralis minor muscle is usually divided at the tendinous portion near its insertion onto the coracoid | Surgery_Schwartz. tissue of the lateral axillary space is elevated as the vein is cleared on its anterior and inferior surfaces. The areo-lar tissues at the junction of the axillary vein and the anterior edge of the latissimus dorsi muscle, which include the lateral and subscapular lymph node groups (level I), are cleared. Care is taken to preserve the thoracodorsal neurovascular bundle. The dissection then continues medially with clearance of the central axillary lymph node group (level II). The long thoracic nerve of Bell is identified and preserved as it travels in the investing fascia of the serratus anterior muscle. Every effort is made to preserve this nerve because permanent disability with a winged scapula and shoulder weakness will follow denervation of the serratus anterior muscle. Patey divided the pectoralis minor and removed it to allow access right up to the apex of the axilla. The pectoralis minor muscle is usually divided at the tendinous portion near its insertion onto the coracoid |
Surgery_Schwartz_4010 | Surgery_Schwartz | the pectoralis minor and removed it to allow access right up to the apex of the axilla. The pectoralis minor muscle is usually divided at the tendinous portion near its insertion onto the coracoid process (Fig. 17-37 inset), which allows dissection of the axillary vein medially to the costoclavicular (Halsted’s) ligament. Finally, the breast and axillary contents are removed from the surgical bed and are sent for pathologic assessment. In his modified radical mastectomy, Patey removed the pectoralis minor muscle. Many surgeons now divide only the tendon of the pectoralis minor muscle at its insertion onto the coracoid process while leaving the rest of the muscle intact, which still provides good access to the apex of the axilla.Figure 17-35. Modified radical mastectomy: eleva-tion of skin flaps. Skin flaps are 7 to 8 mm in thick-ness, inclusive of the skin and telasubcutanea. (Visual Art: © 2013. The University of Texas MD Anderson Cancer Center.)Figure 17-36. Modified radical | Surgery_Schwartz. the pectoralis minor and removed it to allow access right up to the apex of the axilla. The pectoralis minor muscle is usually divided at the tendinous portion near its insertion onto the coracoid process (Fig. 17-37 inset), which allows dissection of the axillary vein medially to the costoclavicular (Halsted’s) ligament. Finally, the breast and axillary contents are removed from the surgical bed and are sent for pathologic assessment. In his modified radical mastectomy, Patey removed the pectoralis minor muscle. Many surgeons now divide only the tendon of the pectoralis minor muscle at its insertion onto the coracoid process while leaving the rest of the muscle intact, which still provides good access to the apex of the axilla.Figure 17-35. Modified radical mastectomy: eleva-tion of skin flaps. Skin flaps are 7 to 8 mm in thick-ness, inclusive of the skin and telasubcutanea. (Visual Art: © 2013. The University of Texas MD Anderson Cancer Center.)Figure 17-36. Modified radical |
Surgery_Schwartz_4011 | Surgery_Schwartz | of skin flaps. Skin flaps are 7 to 8 mm in thick-ness, inclusive of the skin and telasubcutanea. (Visual Art: © 2013. The University of Texas MD Anderson Cancer Center.)Figure 17-36. Modified radical mastectomy after resection of breast tissue. The pectoralis major muscle is cleared of its fascia as the overlying breast is elevated. The latissimus dorsi muscle is the lateral boundary of the dissection. (Visual Art: © 2013. The University of Texas MD Anderson Cancer Center.)Brunicardi_Ch17_p0541-p0612.indd 59201/03/19 5:05 PM 593THE BREASTCHAPTER 17Seromas beneath the skin flaps or in the axilla represent the most frequent complication of mastectomy and axillary lymph node dissection, reportedly occurring in as many as 30% of cases. The use of closed-system suction drainage reduces the incidence of this complication. Catheters are retained in the wound until drainage diminishes to <30 mL per day. Wound infections occur infrequently after a mastectomy, and the majority are a result | Surgery_Schwartz. of skin flaps. Skin flaps are 7 to 8 mm in thick-ness, inclusive of the skin and telasubcutanea. (Visual Art: © 2013. The University of Texas MD Anderson Cancer Center.)Figure 17-36. Modified radical mastectomy after resection of breast tissue. The pectoralis major muscle is cleared of its fascia as the overlying breast is elevated. The latissimus dorsi muscle is the lateral boundary of the dissection. (Visual Art: © 2013. The University of Texas MD Anderson Cancer Center.)Brunicardi_Ch17_p0541-p0612.indd 59201/03/19 5:05 PM 593THE BREASTCHAPTER 17Seromas beneath the skin flaps or in the axilla represent the most frequent complication of mastectomy and axillary lymph node dissection, reportedly occurring in as many as 30% of cases. The use of closed-system suction drainage reduces the incidence of this complication. Catheters are retained in the wound until drainage diminishes to <30 mL per day. Wound infections occur infrequently after a mastectomy, and the majority are a result |
Surgery_Schwartz_4012 | Surgery_Schwartz | incidence of this complication. Catheters are retained in the wound until drainage diminishes to <30 mL per day. Wound infections occur infrequently after a mastectomy, and the majority are a result of skin-flap necrosis. Cultures of speci-mens taken from the infected wound for aerobic and anaerobic organisms, debridement, and antibiotic therapy are effective management. Moderate or severe hemorrhage in the postop-erative period is rare and is best managed with early wound exploration for control of hemorrhage and reestablishment of closed-system suction drainage. The incidence of functionally significant lymphedema after a modified radical mastectomy is approximately 20% but can be as high as 50% to 60% when postoperative radiation is employed. Extensive axillary lymph node dissection, the delivery of radiation therapy, the presence of pathologic lymph nodes, and obesity are predisposing factors. Patients should be referred to physical therapy at the earliest signs of lymphedema to | Surgery_Schwartz. incidence of this complication. Catheters are retained in the wound until drainage diminishes to <30 mL per day. Wound infections occur infrequently after a mastectomy, and the majority are a result of skin-flap necrosis. Cultures of speci-mens taken from the infected wound for aerobic and anaerobic organisms, debridement, and antibiotic therapy are effective management. Moderate or severe hemorrhage in the postop-erative period is rare and is best managed with early wound exploration for control of hemorrhage and reestablishment of closed-system suction drainage. The incidence of functionally significant lymphedema after a modified radical mastectomy is approximately 20% but can be as high as 50% to 60% when postoperative radiation is employed. Extensive axillary lymph node dissection, the delivery of radiation therapy, the presence of pathologic lymph nodes, and obesity are predisposing factors. Patients should be referred to physical therapy at the earliest signs of lymphedema to |
Surgery_Schwartz_4013 | Surgery_Schwartz | the delivery of radiation therapy, the presence of pathologic lymph nodes, and obesity are predisposing factors. Patients should be referred to physical therapy at the earliest signs of lymphedema to prevent progression to the later stages. The use of individually fitted compressive sleeves and complex decongestive therapy may be necessary.Reconstruction of the Breast and Chest WallThe goals of reconstructive surgery after a mastectomy for breast cancer are wound closure and breast reconstruction, which is either immediate or delayed.295 In most cases, wound closure after mastectomy is accomplished with simple approximation of the wound edges. However, if a more radical removal of skin and subcutaneous tissue is necessary, a pedicled myocutane-ous flap from the latissimus dorsi muscle is generally the best approach for wound coverage. A skin graft provides functional coverage that will tolerate adjuvant radiation therapy; however, this is not preferred because poor graft adherence may | Surgery_Schwartz. the delivery of radiation therapy, the presence of pathologic lymph nodes, and obesity are predisposing factors. Patients should be referred to physical therapy at the earliest signs of lymphedema to prevent progression to the later stages. The use of individually fitted compressive sleeves and complex decongestive therapy may be necessary.Reconstruction of the Breast and Chest WallThe goals of reconstructive surgery after a mastectomy for breast cancer are wound closure and breast reconstruction, which is either immediate or delayed.295 In most cases, wound closure after mastectomy is accomplished with simple approximation of the wound edges. However, if a more radical removal of skin and subcutaneous tissue is necessary, a pedicled myocutane-ous flap from the latissimus dorsi muscle is generally the best approach for wound coverage. A skin graft provides functional coverage that will tolerate adjuvant radiation therapy; however, this is not preferred because poor graft adherence may |
Surgery_Schwartz_4014 | Surgery_Schwartz | the best approach for wound coverage. A skin graft provides functional coverage that will tolerate adjuvant radiation therapy; however, this is not preferred because poor graft adherence may delay delivery of radiation therapy. Breast reconstruction after risk-reducing mastectomy or after mastectomy for early-stage breast cancer may be performed at the same time as the mastectomy. This allows for a skin-sparing mastectomy to be performed, which offers the best overall cosmetic outcomes. Reconstruc-tion can proceed with an expander/implant reconstruction or with autologous tissue such as a pedicled myocutaneous flap or a free flap using microvascular techniques. In patients with locally advanced breast cancer, reconstruction is often delayed until after completion of adjuvant radiation therapy to ensure that local-regional control of disease is obtained. The expected use of postmastectomy radiotherapy should also be considered as a reason for delayed reconstruction as radiotherapy to a | Surgery_Schwartz. the best approach for wound coverage. A skin graft provides functional coverage that will tolerate adjuvant radiation therapy; however, this is not preferred because poor graft adherence may delay delivery of radiation therapy. Breast reconstruction after risk-reducing mastectomy or after mastectomy for early-stage breast cancer may be performed at the same time as the mastectomy. This allows for a skin-sparing mastectomy to be performed, which offers the best overall cosmetic outcomes. Reconstruc-tion can proceed with an expander/implant reconstruction or with autologous tissue such as a pedicled myocutaneous flap or a free flap using microvascular techniques. In patients with locally advanced breast cancer, reconstruction is often delayed until after completion of adjuvant radiation therapy to ensure that local-regional control of disease is obtained. The expected use of postmastectomy radiotherapy should also be considered as a reason for delayed reconstruction as radiotherapy to a |
Surgery_Schwartz_4015 | Surgery_Schwartz | to ensure that local-regional control of disease is obtained. The expected use of postmastectomy radiotherapy should also be considered as a reason for delayed reconstruction as radiotherapy to a reconstructed breast has been reported to result in inferior cos-metic outcomes. Consideration can be made for placement of a tissue expander to allow for skin-sparing, but this should be discussed with the radiation oncologist and other members of the treatment team. If chest wall coverage is needed to replace a large skin or soft tissue defect, many different types of myo-cutaneous flaps are employed, but the latissimus dorsi and the rectus abdominis myocutaneous flaps are most frequently used. The latissimus dorsi myocutaneous flap consists of a skin paddle based on the underlying latissimus dorsi muscle, which Figure 17-37. Modified radical mastectomy (Patey): axillary lymph node dissection. The dissection proceeds from lateral to medial, with complete visualization of the anterior and | Surgery_Schwartz. to ensure that local-regional control of disease is obtained. The expected use of postmastectomy radiotherapy should also be considered as a reason for delayed reconstruction as radiotherapy to a reconstructed breast has been reported to result in inferior cos-metic outcomes. Consideration can be made for placement of a tissue expander to allow for skin-sparing, but this should be discussed with the radiation oncologist and other members of the treatment team. If chest wall coverage is needed to replace a large skin or soft tissue defect, many different types of myo-cutaneous flaps are employed, but the latissimus dorsi and the rectus abdominis myocutaneous flaps are most frequently used. The latissimus dorsi myocutaneous flap consists of a skin paddle based on the underlying latissimus dorsi muscle, which Figure 17-37. Modified radical mastectomy (Patey): axillary lymph node dissection. The dissection proceeds from lateral to medial, with complete visualization of the anterior and |
Surgery_Schwartz_4016 | Surgery_Schwartz | dorsi muscle, which Figure 17-37. Modified radical mastectomy (Patey): axillary lymph node dissection. The dissection proceeds from lateral to medial, with complete visualization of the anterior and inferior aspects of the axillary vein. Loose areolar tissue at the junction of the axillary vein and the anterior margin of the latissimus dorsi muscle is swept inferomedially inclusive of the lateral (axillary) lymph node group (level I). Care is taken to preserve the thoracodorsal artery, vein, and nerve in the deep axillary space. The lateral lymph node group is resected in continuity with the subscapular lymph node group (level I) and the external mammary lymph node group (level I). Dissection anterior to the axillary vein allows removal of the central lymph node group (level II) and the apical (subclavicular) lymph node group (level III). The superomedial limit of this dissection is the clavipectoral fascia (Halsted’s ligament). Inset depicts division of the insertion of the | Surgery_Schwartz. dorsi muscle, which Figure 17-37. Modified radical mastectomy (Patey): axillary lymph node dissection. The dissection proceeds from lateral to medial, with complete visualization of the anterior and inferior aspects of the axillary vein. Loose areolar tissue at the junction of the axillary vein and the anterior margin of the latissimus dorsi muscle is swept inferomedially inclusive of the lateral (axillary) lymph node group (level I). Care is taken to preserve the thoracodorsal artery, vein, and nerve in the deep axillary space. The lateral lymph node group is resected in continuity with the subscapular lymph node group (level I) and the external mammary lymph node group (level I). Dissection anterior to the axillary vein allows removal of the central lymph node group (level II) and the apical (subclavicular) lymph node group (level III). The superomedial limit of this dissection is the clavipectoral fascia (Halsted’s ligament). Inset depicts division of the insertion of the |
Surgery_Schwartz_4017 | Surgery_Schwartz | and the apical (subclavicular) lymph node group (level III). The superomedial limit of this dissection is the clavipectoral fascia (Halsted’s ligament). Inset depicts division of the insertion of the pectoralis minor muscle at the coracoid process. The surgeon’s finger shields the underlying brachial plexus. (Reproduced with permission from Bland KI, Copeland EMI: The Breast: Comprehensive Management of Benign and Malignant Diseases, 4th ed. Philadelphia, PA: Elsevier/Saunders; 2009.)Brunicardi_Ch17_p0541-p0612.indd 59301/03/19 5:05 PM 594SPECIFIC CONSIDERATIONSPART IIis supplied by the thoracodorsal artery with contributions from the posterior intercostal arteries. A transverse rectus abdominis myocutaneous (TRAM) flap consists of a skin paddle based on the underlying rectus abdominis muscle, which is supplied by vessels from the deep inferior epigastric artery. The free TRAM flap uses microvascular anastomoses to establish blood supply to the flap. When the bony chest wall is | Surgery_Schwartz. and the apical (subclavicular) lymph node group (level III). The superomedial limit of this dissection is the clavipectoral fascia (Halsted’s ligament). Inset depicts division of the insertion of the pectoralis minor muscle at the coracoid process. The surgeon’s finger shields the underlying brachial plexus. (Reproduced with permission from Bland KI, Copeland EMI: The Breast: Comprehensive Management of Benign and Malignant Diseases, 4th ed. Philadelphia, PA: Elsevier/Saunders; 2009.)Brunicardi_Ch17_p0541-p0612.indd 59301/03/19 5:05 PM 594SPECIFIC CONSIDERATIONSPART IIis supplied by the thoracodorsal artery with contributions from the posterior intercostal arteries. A transverse rectus abdominis myocutaneous (TRAM) flap consists of a skin paddle based on the underlying rectus abdominis muscle, which is supplied by vessels from the deep inferior epigastric artery. The free TRAM flap uses microvascular anastomoses to establish blood supply to the flap. When the bony chest wall is |
Surgery_Schwartz_4018 | Surgery_Schwartz | muscle, which is supplied by vessels from the deep inferior epigastric artery. The free TRAM flap uses microvascular anastomoses to establish blood supply to the flap. When the bony chest wall is involved with cancer, resection of a portion of the bony chest wall is indicated. If only one or two ribs are resected and soft tissue coverage is pro-vided, reconstruction of the bony defect is usually not necessary because scar tissue will stabilize the chest wall. If more than two ribs are sacrificed, it is advisable to stabilize the chest wall with prosthetic material, which is then covered with soft tissue by using a latissimus dorsi or TRAM flap.NONSURGICAL BREAST CANCER THERAPIESRadiation TherapyRadiation therapy is used for all stages of breast cancer depending on whether the patient is undergoing BCT or mas-tectomy.296-302 Adjuvant radiation for patients with DCIS and early-stage breast cancer have been described previously in this chapter. Those women treated with mastectomy who | Surgery_Schwartz. muscle, which is supplied by vessels from the deep inferior epigastric artery. The free TRAM flap uses microvascular anastomoses to establish blood supply to the flap. When the bony chest wall is involved with cancer, resection of a portion of the bony chest wall is indicated. If only one or two ribs are resected and soft tissue coverage is pro-vided, reconstruction of the bony defect is usually not necessary because scar tissue will stabilize the chest wall. If more than two ribs are sacrificed, it is advisable to stabilize the chest wall with prosthetic material, which is then covered with soft tissue by using a latissimus dorsi or TRAM flap.NONSURGICAL BREAST CANCER THERAPIESRadiation TherapyRadiation therapy is used for all stages of breast cancer depending on whether the patient is undergoing BCT or mas-tectomy.296-302 Adjuvant radiation for patients with DCIS and early-stage breast cancer have been described previously in this chapter. Those women treated with mastectomy who |
Surgery_Schwartz_4019 | Surgery_Schwartz | undergoing BCT or mas-tectomy.296-302 Adjuvant radiation for patients with DCIS and early-stage breast cancer have been described previously in this chapter. Those women treated with mastectomy who have cancer at the surgical margins are at sufficiently high risk for local recurrence to warrant the use of adjuvant radiation therapy to the chest wall postoperatively. Women with metastatic disease involving four or more axillary lymph nodes and premeno-pausal women with metastatic disease involving one to three lymph nodes also are at increased risk for recurrence and are candidates for the use of chest wall and supraclavicular lymph node radiation therapy. In advanced local-regional breast can-cer (stage IIIA or IIIB), women are at high risk for recurrent disease after surgical therapy, and adjuvant radiation therapy is used to reduce the risk of recurrence. Current recommenda-tions for stages IIIA and IIIB breast cancer are (a) adjuvant radiation therapy to the breast and | Surgery_Schwartz. undergoing BCT or mas-tectomy.296-302 Adjuvant radiation for patients with DCIS and early-stage breast cancer have been described previously in this chapter. Those women treated with mastectomy who have cancer at the surgical margins are at sufficiently high risk for local recurrence to warrant the use of adjuvant radiation therapy to the chest wall postoperatively. Women with metastatic disease involving four or more axillary lymph nodes and premeno-pausal women with metastatic disease involving one to three lymph nodes also are at increased risk for recurrence and are candidates for the use of chest wall and supraclavicular lymph node radiation therapy. In advanced local-regional breast can-cer (stage IIIA or IIIB), women are at high risk for recurrent disease after surgical therapy, and adjuvant radiation therapy is used to reduce the risk of recurrence. Current recommenda-tions for stages IIIA and IIIB breast cancer are (a) adjuvant radiation therapy to the breast and |
Surgery_Schwartz_4020 | Surgery_Schwartz | therapy, and adjuvant radiation therapy is used to reduce the risk of recurrence. Current recommenda-tions for stages IIIA and IIIB breast cancer are (a) adjuvant radiation therapy to the breast and supraclavicular lymph nodes after neoadjuvant chemotherapy and segmental mastectomy with or without axillary lymph node dissection, (b) adjuvant radiation therapy to the chest wall and supraclavicular lymph nodes after neoadjuvant chemotherapy and mastectomy with or without axillary lymph node dissection, and (c) adjuvant radiation therapy to the chest wall and supraclavicular lymph nodes after segmental mastectomy or mastectomy with axillary lymph node dissection and adjuvant chemotherapy. Data from the EBCTCG has shown improvements in local-regional con-trol and survival in patients treated with mastectomy and post-mastectomy radiation therapy for one to three positive axillary lymph nodes.303 This data is based on clinical trials from the era of axillary lymph node dissection for | Surgery_Schwartz. therapy, and adjuvant radiation therapy is used to reduce the risk of recurrence. Current recommenda-tions for stages IIIA and IIIB breast cancer are (a) adjuvant radiation therapy to the breast and supraclavicular lymph nodes after neoadjuvant chemotherapy and segmental mastectomy with or without axillary lymph node dissection, (b) adjuvant radiation therapy to the chest wall and supraclavicular lymph nodes after neoadjuvant chemotherapy and mastectomy with or without axillary lymph node dissection, and (c) adjuvant radiation therapy to the chest wall and supraclavicular lymph nodes after segmental mastectomy or mastectomy with axillary lymph node dissection and adjuvant chemotherapy. Data from the EBCTCG has shown improvements in local-regional con-trol and survival in patients treated with mastectomy and post-mastectomy radiation therapy for one to three positive axillary lymph nodes.303 This data is based on clinical trials from the era of axillary lymph node dissection for |
Surgery_Schwartz_4021 | Surgery_Schwartz | with mastectomy and post-mastectomy radiation therapy for one to three positive axillary lymph nodes.303 This data is based on clinical trials from the era of axillary lymph node dissection for staging prior to the routine use of sentinel lymph node dissection. It is likely that the vol-ume of disease in the earlier trials was greater overall than what is currently seen in patients who have small volume metastases detected at sentinel node dissection. It is important to include all multidisciplinary team members (medical oncology, plastic surgery, radiation oncology, and surgical oncology) regarding the risks and benefits of postmastectomy radiation therapy in patients with one to three positive nodes.The use of partial breast irradiation (APBI) for patients treated with breast-conserving surgery has also been previously described. APBI can be delivered via brachytherapy, external beam radiation therapy using 3D conformal radiation, or inten-sity-modulated radiation therapy. Although | Surgery_Schwartz. with mastectomy and post-mastectomy radiation therapy for one to three positive axillary lymph nodes.303 This data is based on clinical trials from the era of axillary lymph node dissection for staging prior to the routine use of sentinel lymph node dissection. It is likely that the vol-ume of disease in the earlier trials was greater overall than what is currently seen in patients who have small volume metastases detected at sentinel node dissection. It is important to include all multidisciplinary team members (medical oncology, plastic surgery, radiation oncology, and surgical oncology) regarding the risks and benefits of postmastectomy radiation therapy in patients with one to three positive nodes.The use of partial breast irradiation (APBI) for patients treated with breast-conserving surgery has also been previously described. APBI can be delivered via brachytherapy, external beam radiation therapy using 3D conformal radiation, or inten-sity-modulated radiation therapy. Although |
Surgery_Schwartz_4022 | Surgery_Schwartz | surgery has also been previously described. APBI can be delivered via brachytherapy, external beam radiation therapy using 3D conformal radiation, or inten-sity-modulated radiation therapy. Although initial results are Table 17-14Adjuvant chemotherapy regimens for breast cancerHER-2 NEGATIVEHER-2 POSITIVEPreferred Dose dense AC → Paclitaxel every 2 weeksDose dense AC → Paclitaxel weeklyTC (T = docetaxel)Other RegimensCMFAC → Docetaxel every 3 weeksAC → Paclitaxel weeklyTAC (T = docetaxel)AC → T + trastuzumab +/pertuzumab (T = paclitaxel)TCH (docetaxel, carboplatin, trastuzumab +/pertuzumab)Other RegimensAC → T + trastuzumab +/pertuzumab (T = docetaxel)Docetaxel + cyclophosphamide + trastuzumabFEC → Docetaxel + trastuzumab + pertuzumabFEC → Paclitaxel + trastuzumab + pertuzumabPaclitaxel + trastuzumabPaclitaxel + trastuzumab + pertuzumab → FECDocetaxel + trastuzumab + pertuzumab → FECA = Adriamycin (doxorubicin); C = cyclophosphamide; E = epirubicin; F = 5-fluorouracil; M = | Surgery_Schwartz. surgery has also been previously described. APBI can be delivered via brachytherapy, external beam radiation therapy using 3D conformal radiation, or inten-sity-modulated radiation therapy. Although initial results are Table 17-14Adjuvant chemotherapy regimens for breast cancerHER-2 NEGATIVEHER-2 POSITIVEPreferred Dose dense AC → Paclitaxel every 2 weeksDose dense AC → Paclitaxel weeklyTC (T = docetaxel)Other RegimensCMFAC → Docetaxel every 3 weeksAC → Paclitaxel weeklyTAC (T = docetaxel)AC → T + trastuzumab +/pertuzumab (T = paclitaxel)TCH (docetaxel, carboplatin, trastuzumab +/pertuzumab)Other RegimensAC → T + trastuzumab +/pertuzumab (T = docetaxel)Docetaxel + cyclophosphamide + trastuzumabFEC → Docetaxel + trastuzumab + pertuzumabFEC → Paclitaxel + trastuzumab + pertuzumabPaclitaxel + trastuzumabPaclitaxel + trastuzumab + pertuzumab → FECDocetaxel + trastuzumab + pertuzumab → FECA = Adriamycin (doxorubicin); C = cyclophosphamide; E = epirubicin; F = 5-fluorouracil; M = |
Surgery_Schwartz_4023 | Surgery_Schwartz | + trastuzumabPaclitaxel + trastuzumab + pertuzumab → FECDocetaxel + trastuzumab + pertuzumab → FECA = Adriamycin (doxorubicin); C = cyclophosphamide; E = epirubicin; F = 5-fluorouracil; M = methotrexate; T = Taxane (docetaxel or paclitaxel); → = followed by.Data from NCCN Practice Guidelines in Oncology. Fort Washington, PA: National Comprehensive Cancer Network, 2006.promising in highly selected low-risk populations, use of APBI should be based on current guidelines or offered in the setting of a prospective trial.304Chemotherapy AdjuvantChemotherapy. The Early Breast Cancer Trialists’ Collabora-tive Group overview analysis of adjuvant chemotherapy demon-strated reductions in the odds of recurrence and death in women ≤70 years of age with stage I, IIA, or IIB breast cancer.123,305-309 For those ≥70 years of age, the lack of definitive clinical trial data regarding adjuvant chemotherapy prevented definitive rec-ommendations. Adjuvant chemotherapy is of minimal benefit to women with | Surgery_Schwartz. + trastuzumabPaclitaxel + trastuzumab + pertuzumab → FECDocetaxel + trastuzumab + pertuzumab → FECA = Adriamycin (doxorubicin); C = cyclophosphamide; E = epirubicin; F = 5-fluorouracil; M = methotrexate; T = Taxane (docetaxel or paclitaxel); → = followed by.Data from NCCN Practice Guidelines in Oncology. Fort Washington, PA: National Comprehensive Cancer Network, 2006.promising in highly selected low-risk populations, use of APBI should be based on current guidelines or offered in the setting of a prospective trial.304Chemotherapy AdjuvantChemotherapy. The Early Breast Cancer Trialists’ Collabora-tive Group overview analysis of adjuvant chemotherapy demon-strated reductions in the odds of recurrence and death in women ≤70 years of age with stage I, IIA, or IIB breast cancer.123,305-309 For those ≥70 years of age, the lack of definitive clinical trial data regarding adjuvant chemotherapy prevented definitive rec-ommendations. Adjuvant chemotherapy is of minimal benefit to women with |
Surgery_Schwartz_4024 | Surgery_Schwartz | For those ≥70 years of age, the lack of definitive clinical trial data regarding adjuvant chemotherapy prevented definitive rec-ommendations. Adjuvant chemotherapy is of minimal benefit to women with negative nodes and cancers ≤0.5 cm in size and is not recommended. Women with negative nodes and cancers 0.6 to 1.0 cm are divided into those with a low risk of recurrence and those with unfavorable prognostic features that portend a higher risk of recurrence and a need for adjuvant chemotherapy. Adverse prognostic factors include blood vessel or lymph ves-sel invasion, high nuclear grade, high histologic grade, HER2/neu overexpression, and negative hormone receptor status. American Society of Clinical Oncology guidelines suggest that adjuvant chemotherapy should be considered for patients with positive lymph nodes, HER2-positive disease, Adjuvant! Online mortality greater than 10%, grade 3 lymph node negative tumors >5 mm, triple-negative tumors, lympho-vascular invasion, or estimated | Surgery_Schwartz. For those ≥70 years of age, the lack of definitive clinical trial data regarding adjuvant chemotherapy prevented definitive rec-ommendations. Adjuvant chemotherapy is of minimal benefit to women with negative nodes and cancers ≤0.5 cm in size and is not recommended. Women with negative nodes and cancers 0.6 to 1.0 cm are divided into those with a low risk of recurrence and those with unfavorable prognostic features that portend a higher risk of recurrence and a need for adjuvant chemotherapy. Adverse prognostic factors include blood vessel or lymph ves-sel invasion, high nuclear grade, high histologic grade, HER2/neu overexpression, and negative hormone receptor status. American Society of Clinical Oncology guidelines suggest that adjuvant chemotherapy should be considered for patients with positive lymph nodes, HER2-positive disease, Adjuvant! Online mortality greater than 10%, grade 3 lymph node negative tumors >5 mm, triple-negative tumors, lympho-vascular invasion, or estimated |
Surgery_Schwartz_4025 | Surgery_Schwartz | with positive lymph nodes, HER2-positive disease, Adjuvant! Online mortality greater than 10%, grade 3 lymph node negative tumors >5 mm, triple-negative tumors, lympho-vascular invasion, or estimated distant relapse risk of greater than 15% at 10 years based on 21 gene recurrence score.259 Adjuvant chemotherapy is recommended by the NCCN guidelines for women with these unfavorable prognostic features. Table 17-14 lists the frequently used chemotherapy regimens for breast cancer.For women with hormone receptor-negative cancers that are >1 cm in size, adjuvant chemotherapy is appropriate. Brunicardi_Ch17_p0541-p0612.indd 59401/03/19 5:05 PM 595THE BREASTCHAPTER 17However, women with node-negative hormone receptor–positive cancers and T1 tumors are candidates for antiestrogen therapy with or without chemotherapy. Assessment of overall risk using known prognostic factors or additional testing such as the 21-gene recurrence score assay can help to guide deci-sion making regarding | Surgery_Schwartz. with positive lymph nodes, HER2-positive disease, Adjuvant! Online mortality greater than 10%, grade 3 lymph node negative tumors >5 mm, triple-negative tumors, lympho-vascular invasion, or estimated distant relapse risk of greater than 15% at 10 years based on 21 gene recurrence score.259 Adjuvant chemotherapy is recommended by the NCCN guidelines for women with these unfavorable prognostic features. Table 17-14 lists the frequently used chemotherapy regimens for breast cancer.For women with hormone receptor-negative cancers that are >1 cm in size, adjuvant chemotherapy is appropriate. Brunicardi_Ch17_p0541-p0612.indd 59401/03/19 5:05 PM 595THE BREASTCHAPTER 17However, women with node-negative hormone receptor–positive cancers and T1 tumors are candidates for antiestrogen therapy with or without chemotherapy. Assessment of overall risk using known prognostic factors or additional testing such as the 21-gene recurrence score assay can help to guide deci-sion making regarding |
Surgery_Schwartz_4026 | Surgery_Schwartz | with or without chemotherapy. Assessment of overall risk using known prognostic factors or additional testing such as the 21-gene recurrence score assay can help to guide deci-sion making regarding chemotherapy in patients with node-negative, ER-positive breast cancer. For special-type cancers (tubular, mucinous, medullary, etc), which are usually strongly estrogen receptor positive, adjuvant antiestrogen therapy should be advised for cancers >1 cm. For women with node-positive tumors or with a special-type cancer that is >3 cm, the use of chemotherapy is appropriate; those with hormone receptor-positive tumors should receive antiestrogen therapy.For stage IIIA breast cancer, preoperative chemotherapy with an anthracycline and taxane-containing regimen followed by either a modified radical mastectomy or segmental mastec-tomy with axillary dissection followed by adjuvant radiation therapy should be considered, especially for estrogen receptor negative disease. While the same regimen | Surgery_Schwartz. with or without chemotherapy. Assessment of overall risk using known prognostic factors or additional testing such as the 21-gene recurrence score assay can help to guide deci-sion making regarding chemotherapy in patients with node-negative, ER-positive breast cancer. For special-type cancers (tubular, mucinous, medullary, etc), which are usually strongly estrogen receptor positive, adjuvant antiestrogen therapy should be advised for cancers >1 cm. For women with node-positive tumors or with a special-type cancer that is >3 cm, the use of chemotherapy is appropriate; those with hormone receptor-positive tumors should receive antiestrogen therapy.For stage IIIA breast cancer, preoperative chemotherapy with an anthracycline and taxane-containing regimen followed by either a modified radical mastectomy or segmental mastec-tomy with axillary dissection followed by adjuvant radiation therapy should be considered, especially for estrogen receptor negative disease. While the same regimen |
Surgery_Schwartz_4027 | Surgery_Schwartz | mastectomy or segmental mastec-tomy with axillary dissection followed by adjuvant radiation therapy should be considered, especially for estrogen receptor negative disease. While the same regimen may be considered for estrogen receptor positive disease, it is known that these tumors respond less well to chemotherapy with <10% pCR rate overall and <3% pCR rate for lobular cancers. Other options such as neoadjuvant endocrine therapy followed by local-regional treatment or in some cases primary endocrine therapy may be considered depending on other tumor characteristics and the patient’s comorbid conditions and preference.Neoadjuvant (Preoperative) Chemotherapy. In the early 1970s, the National Cancer Institute in Milan, Italy, initiated two prospective randomized multimodality clinical trials for women with T3 or T4 breast cancer.310 The best results were achieved when surgery was interposed between chemotherapy courses, with 82% local-regional control and 25% having a 5-year | Surgery_Schwartz. mastectomy or segmental mastec-tomy with axillary dissection followed by adjuvant radiation therapy should be considered, especially for estrogen receptor negative disease. While the same regimen may be considered for estrogen receptor positive disease, it is known that these tumors respond less well to chemotherapy with <10% pCR rate overall and <3% pCR rate for lobular cancers. Other options such as neoadjuvant endocrine therapy followed by local-regional treatment or in some cases primary endocrine therapy may be considered depending on other tumor characteristics and the patient’s comorbid conditions and preference.Neoadjuvant (Preoperative) Chemotherapy. In the early 1970s, the National Cancer Institute in Milan, Italy, initiated two prospective randomized multimodality clinical trials for women with T3 or T4 breast cancer.310 The best results were achieved when surgery was interposed between chemotherapy courses, with 82% local-regional control and 25% having a 5-year |
Surgery_Schwartz_4028 | Surgery_Schwartz | trials for women with T3 or T4 breast cancer.310 The best results were achieved when surgery was interposed between chemotherapy courses, with 82% local-regional control and 25% having a 5-year dis-ease-free survival. The NSABP B-18 trial evaluated the role of neoadjuvant chemotherapy in women with operable stages II and III breast cancer.206 Women entered into this study were randomly assigned to receive either surgery followed by che-motherapy or neoadjuvant chemotherapy followed by surgery. There was no difference in the 5-year disease-free survival rates for the two groups, but after neoadjuvant chemotherapy there was an increase in the number of lumpectomies performed and a decreased incidence of node positivity. It was suggested that neoadjuvant chemotherapy be considered for the initial manage-ment of breast cancers judged too large for initial lumpectomy.Several prospective clinical trials have evaluated the neo-adjuvant approach, and two meta-analyses have been performed, | Surgery_Schwartz. trials for women with T3 or T4 breast cancer.310 The best results were achieved when surgery was interposed between chemotherapy courses, with 82% local-regional control and 25% having a 5-year dis-ease-free survival. The NSABP B-18 trial evaluated the role of neoadjuvant chemotherapy in women with operable stages II and III breast cancer.206 Women entered into this study were randomly assigned to receive either surgery followed by che-motherapy or neoadjuvant chemotherapy followed by surgery. There was no difference in the 5-year disease-free survival rates for the two groups, but after neoadjuvant chemotherapy there was an increase in the number of lumpectomies performed and a decreased incidence of node positivity. It was suggested that neoadjuvant chemotherapy be considered for the initial manage-ment of breast cancers judged too large for initial lumpectomy.Several prospective clinical trials have evaluated the neo-adjuvant approach, and two meta-analyses have been performed, |
Surgery_Schwartz_4029 | Surgery_Schwartz | initial manage-ment of breast cancers judged too large for initial lumpectomy.Several prospective clinical trials have evaluated the neo-adjuvant approach, and two meta-analyses have been performed, each showing that neoadjuvant vs. adjuvant chemotherapy are equivalent in terms of OS.262,311 These analyses also evaluated local-regional recurrence (LRR) and found that there was an increase in LRR rates for patients receiving neoadjuvant chemo-therapy when radiation therapy was used alone without surgery after completion of chemotherapy. Mittendorf and colleagues evaluated a contemporary series of almost 3000 patients treated with breast conserving surgery and radiation therapy who received either neoadjuvant or adjuvant chemotherapy for breast cancer.312 They found that the risk of LRR was driven by bio-logic factors and disease stage and was not impacted by the timing of chemotherapy delivery. These data high-light the importance of the multidisciplinary management of patients with | Surgery_Schwartz. initial manage-ment of breast cancers judged too large for initial lumpectomy.Several prospective clinical trials have evaluated the neo-adjuvant approach, and two meta-analyses have been performed, each showing that neoadjuvant vs. adjuvant chemotherapy are equivalent in terms of OS.262,311 These analyses also evaluated local-regional recurrence (LRR) and found that there was an increase in LRR rates for patients receiving neoadjuvant chemo-therapy when radiation therapy was used alone without surgery after completion of chemotherapy. Mittendorf and colleagues evaluated a contemporary series of almost 3000 patients treated with breast conserving surgery and radiation therapy who received either neoadjuvant or adjuvant chemotherapy for breast cancer.312 They found that the risk of LRR was driven by bio-logic factors and disease stage and was not impacted by the timing of chemotherapy delivery. These data high-light the importance of the multidisciplinary management of patients with |
Surgery_Schwartz_4030 | Surgery_Schwartz | driven by bio-logic factors and disease stage and was not impacted by the timing of chemotherapy delivery. These data high-light the importance of the multidisciplinary management of patients with breast cancer in achieving the best outcomes.The use of neoadjuvant chemotherapy offers the oppor-tunity to observe the response of the intact primary tumor 10and any regional nodal metastases to a specific chemotherapy regimen.279 For patients whose tumors remain stable in size or even progress with the initial neoadjuvant chemotherapy regi-men, a new regimen may be considered that uses another class of agents, although there is no randomized data confirming this will improve outcome.After treatment with neoadjuvant chemotherapy, patients are assessed for clinical and pathologic response to the regimen. Patients whose tumors achieve a pathologic complete response to neoadjuvant chemotherapy have been shown to have statisti-cally improved survival outcomes to those of patients whose tumors | Surgery_Schwartz. driven by bio-logic factors and disease stage and was not impacted by the timing of chemotherapy delivery. These data high-light the importance of the multidisciplinary management of patients with breast cancer in achieving the best outcomes.The use of neoadjuvant chemotherapy offers the oppor-tunity to observe the response of the intact primary tumor 10and any regional nodal metastases to a specific chemotherapy regimen.279 For patients whose tumors remain stable in size or even progress with the initial neoadjuvant chemotherapy regi-men, a new regimen may be considered that uses another class of agents, although there is no randomized data confirming this will improve outcome.After treatment with neoadjuvant chemotherapy, patients are assessed for clinical and pathologic response to the regimen. Patients whose tumors achieve a pathologic complete response to neoadjuvant chemotherapy have been shown to have statisti-cally improved survival outcomes to those of patients whose tumors |
Surgery_Schwartz_4031 | Surgery_Schwartz | regimen. Patients whose tumors achieve a pathologic complete response to neoadjuvant chemotherapy have been shown to have statisti-cally improved survival outcomes to those of patients whose tumors demonstrate only a partial response, remain stable, or progress on treatment. Researchers at MD Anderson Cancer Center have shown that residual cancer burden (RCB)—categorized into four classes, RCB-0 or pathologic complete response, RCB-1, RCB-2, and RCB-3—is predictive of 10-year relapse-free survival with neoadjuvant chemotherapy in triple negative, ER-positive, and HER2-positive tumors.313 Patients who experience progression of disease during neoadjuvant che-motherapy have the poorest survival.314,315 This means that while patients who achieve a pCR will have a better prognosis based on their response to neoadjuvant chemotherapy. Equally other patients will have a poorer prognosis compared to when they started neoadjuvant therapy based on the nonresponse to treat-ment. Consequently, | Surgery_Schwartz. regimen. Patients whose tumors achieve a pathologic complete response to neoadjuvant chemotherapy have been shown to have statisti-cally improved survival outcomes to those of patients whose tumors demonstrate only a partial response, remain stable, or progress on treatment. Researchers at MD Anderson Cancer Center have shown that residual cancer burden (RCB)—categorized into four classes, RCB-0 or pathologic complete response, RCB-1, RCB-2, and RCB-3—is predictive of 10-year relapse-free survival with neoadjuvant chemotherapy in triple negative, ER-positive, and HER2-positive tumors.313 Patients who experience progression of disease during neoadjuvant che-motherapy have the poorest survival.314,315 This means that while patients who achieve a pCR will have a better prognosis based on their response to neoadjuvant chemotherapy. Equally other patients will have a poorer prognosis compared to when they started neoadjuvant therapy based on the nonresponse to treat-ment. Consequently, |
Surgery_Schwartz_4032 | Surgery_Schwartz | their response to neoadjuvant chemotherapy. Equally other patients will have a poorer prognosis compared to when they started neoadjuvant therapy based on the nonresponse to treat-ment. Consequently, the FDA has supported the use of the neo-adjuvant platform and pathologic response rates as an endpoint for mechanism of accelerated approval for new agents in high risk early stage breast cancer, though the short-term endpoints (i.e., pCR) have not been shown to correlate with long-term out-comes (i.e., disease free survival and overall survival).Current NCCN recommendations for treatment of oper-able advanced local-regional breast cancer are neoadjuvant chemotherapy with an anthracycline-containing or taxane-containing regimen or both, followed by mastectomy or lumpec-tomy with axillary lymph node dissection if necessary, followed by adjuvant radiation therapy. For patients with HER2-positive breast cancer, trastuzumab and pertuzumab can be combined with chemotherapy in the preoperative | Surgery_Schwartz. their response to neoadjuvant chemotherapy. Equally other patients will have a poorer prognosis compared to when they started neoadjuvant therapy based on the nonresponse to treat-ment. Consequently, the FDA has supported the use of the neo-adjuvant platform and pathologic response rates as an endpoint for mechanism of accelerated approval for new agents in high risk early stage breast cancer, though the short-term endpoints (i.e., pCR) have not been shown to correlate with long-term out-comes (i.e., disease free survival and overall survival).Current NCCN recommendations for treatment of oper-able advanced local-regional breast cancer are neoadjuvant chemotherapy with an anthracycline-containing or taxane-containing regimen or both, followed by mastectomy or lumpec-tomy with axillary lymph node dissection if necessary, followed by adjuvant radiation therapy. For patients with HER2-positive breast cancer, trastuzumab and pertuzumab can be combined with chemotherapy in the preoperative |
Surgery_Schwartz_4033 | Surgery_Schwartz | node dissection if necessary, followed by adjuvant radiation therapy. For patients with HER2-positive breast cancer, trastuzumab and pertuzumab can be combined with chemotherapy in the preoperative setting to increase patho-logic complete response rates. For inoperable stage IIIA and for stage IIIB breast cancer, neoadjuvant chemotherapy is used to decrease the local-regional cancer burden. This may then permit subsequent modified radical or radical mastectomy, which is followed by adjuvant radiation therapy.Nodal Evaluation in Patients Receiving Neoadjuvant Chemotherapy. The management of the axilla after neoadjuvant chemotherapy has not been specifically addressed in randomized trials. Standard practice has been to perform an axillary lymph node dissection after chemotherapy or to perform a sentinel lymph node dissection before chemotherapy for nodal staging before chemotherapy is initiated. A number of small single-institution studies, one multicenter study, and a recent | Surgery_Schwartz. node dissection if necessary, followed by adjuvant radiation therapy. For patients with HER2-positive breast cancer, trastuzumab and pertuzumab can be combined with chemotherapy in the preoperative setting to increase patho-logic complete response rates. For inoperable stage IIIA and for stage IIIB breast cancer, neoadjuvant chemotherapy is used to decrease the local-regional cancer burden. This may then permit subsequent modified radical or radical mastectomy, which is followed by adjuvant radiation therapy.Nodal Evaluation in Patients Receiving Neoadjuvant Chemotherapy. The management of the axilla after neoadjuvant chemotherapy has not been specifically addressed in randomized trials. Standard practice has been to perform an axillary lymph node dissection after chemotherapy or to perform a sentinel lymph node dissection before chemotherapy for nodal staging before chemotherapy is initiated. A number of small single-institution studies, one multicenter study, and a recent |
Surgery_Schwartz_4034 | Surgery_Schwartz | to perform a sentinel lymph node dissection before chemotherapy for nodal staging before chemotherapy is initiated. A number of small single-institution studies, one multicenter study, and a recent meta-analysis have explored the use of SLN dissection at the completion of chemo-therapy. The published results from these studies have demon-strated the feasibility of SLN dissection in breast cancer patients after neoadjuvant chemotherapy. A review of 14 studies with 818 patients showed a false negative rate of 11% with an overall accu-racy of 94%.280,281,316 While SLN dissection has been accepted for assessment of the axilla in the clinically node-negative axilla after neoadjuvant chemotherapy, clinicians have been slower to adopt this approach for axillary staging after chemotherapy in patients who started with initial node-positive disease. Several clinical Brunicardi_Ch17_p0541-p0612.indd 59501/03/19 5:05 PM 596SPECIFIC CONSIDERATIONSPART IItrials have been performed to evaluate | Surgery_Schwartz. to perform a sentinel lymph node dissection before chemotherapy for nodal staging before chemotherapy is initiated. A number of small single-institution studies, one multicenter study, and a recent meta-analysis have explored the use of SLN dissection at the completion of chemo-therapy. The published results from these studies have demon-strated the feasibility of SLN dissection in breast cancer patients after neoadjuvant chemotherapy. A review of 14 studies with 818 patients showed a false negative rate of 11% with an overall accu-racy of 94%.280,281,316 While SLN dissection has been accepted for assessment of the axilla in the clinically node-negative axilla after neoadjuvant chemotherapy, clinicians have been slower to adopt this approach for axillary staging after chemotherapy in patients who started with initial node-positive disease. Several clinical Brunicardi_Ch17_p0541-p0612.indd 59501/03/19 5:05 PM 596SPECIFIC CONSIDERATIONSPART IItrials have been performed to evaluate |
Surgery_Schwartz_4035 | Surgery_Schwartz | who started with initial node-positive disease. Several clinical Brunicardi_Ch17_p0541-p0612.indd 59501/03/19 5:05 PM 596SPECIFIC CONSIDERATIONSPART IItrials have been performed to evaluate the accuracy of SLN dis-section in patients with documented axillary metastases at initial presentation, including ACOSOG Z1071, SENTINA, and SN FNAC. ACOSOG Z1071 (Alliance) analyzed women with clini-cal T0-T4, N1-N2, M0 breast cancer who underwent both SLN surgery and axillary lymph node dissection (ALND).317 The pri-mary endpoint was the false-negative rate (FNR) of SLN surgery after chemotherapy with clinically node-positive disease with a prespecified endpoint of 10% considered to be an acceptable rate. However, the FNR was found to be 12.6%, though it was lower when dual-agent mapping technique was used and at least three or more SLNs removed.317 The SENTINA and SN FNAC trials had findings similar to Z1071. The results from Z1071 were further analyzed to determine if a clip was placed in | Surgery_Schwartz. who started with initial node-positive disease. Several clinical Brunicardi_Ch17_p0541-p0612.indd 59501/03/19 5:05 PM 596SPECIFIC CONSIDERATIONSPART IItrials have been performed to evaluate the accuracy of SLN dis-section in patients with documented axillary metastases at initial presentation, including ACOSOG Z1071, SENTINA, and SN FNAC. ACOSOG Z1071 (Alliance) analyzed women with clini-cal T0-T4, N1-N2, M0 breast cancer who underwent both SLN surgery and axillary lymph node dissection (ALND).317 The pri-mary endpoint was the false-negative rate (FNR) of SLN surgery after chemotherapy with clinically node-positive disease with a prespecified endpoint of 10% considered to be an acceptable rate. However, the FNR was found to be 12.6%, though it was lower when dual-agent mapping technique was used and at least three or more SLNs removed.317 The SENTINA and SN FNAC trials had findings similar to Z1071. The results from Z1071 were further analyzed to determine if a clip was placed in |
Surgery_Schwartz_4036 | Surgery_Schwartz | was used and at least three or more SLNs removed.317 The SENTINA and SN FNAC trials had findings similar to Z1071. The results from Z1071 were further analyzed to determine if a clip was placed in the positive node at initial diagnosis and if the clipped node location at surgery (SLN or ALND) was evaluated. Indeed, this showed that identification of the clipped node during the surgical procedure further decreased the FNR.318 The results from the ACOSOG Z1071 (Alliance) trial, in cases presenting with cN1 disease and at least two SLN resec-tions and clipped node was within the SLN specimen, showed that the FNR was 6.8%.318 Caudle et al at MD Anderson Cancer Center performed a prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the biopsy-proven lymph node, who were treated with neoadjuvant chemotherapy; at the time of surgery these patients underwent SLN dissection with targeting and removal of the clipped node (targeted axillary dis-section | Surgery_Schwartz. was used and at least three or more SLNs removed.317 The SENTINA and SN FNAC trials had findings similar to Z1071. The results from Z1071 were further analyzed to determine if a clip was placed in the positive node at initial diagnosis and if the clipped node location at surgery (SLN or ALND) was evaluated. Indeed, this showed that identification of the clipped node during the surgical procedure further decreased the FNR.318 The results from the ACOSOG Z1071 (Alliance) trial, in cases presenting with cN1 disease and at least two SLN resec-tions and clipped node was within the SLN specimen, showed that the FNR was 6.8%.318 Caudle et al at MD Anderson Cancer Center performed a prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the biopsy-proven lymph node, who were treated with neoadjuvant chemotherapy; at the time of surgery these patients underwent SLN dissection with targeting and removal of the clipped node (targeted axillary dis-section |
Surgery_Schwartz_4037 | Surgery_Schwartz | node, who were treated with neoadjuvant chemotherapy; at the time of surgery these patients underwent SLN dissection with targeting and removal of the clipped node (targeted axillary dis-section [TAD]).319 TAD includes SLN surgery and selective local-ization and removal of the clipped node, with the goal to determine if pathologic changes in the clipped node accurately reflect the status of the nodal basin, and proposing that TAD improves the FNR compared to SLN surgery alone.319 In patients undergoing SLN surgery and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2–19.8), and adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03–7.3; P = .03). TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05–10.7).319 Although the use of dual tracer tech-nique, retrieval of three or more SLNs, and TAD improve axillary staging after neoadjuvant chemotherapy, there is no long-term data about the oncologic safety of omitting ALND in | Surgery_Schwartz. node, who were treated with neoadjuvant chemotherapy; at the time of surgery these patients underwent SLN dissection with targeting and removal of the clipped node (targeted axillary dis-section [TAD]).319 TAD includes SLN surgery and selective local-ization and removal of the clipped node, with the goal to determine if pathologic changes in the clipped node accurately reflect the status of the nodal basin, and proposing that TAD improves the FNR compared to SLN surgery alone.319 In patients undergoing SLN surgery and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2–19.8), and adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03–7.3; P = .03). TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05–10.7).319 Although the use of dual tracer tech-nique, retrieval of three or more SLNs, and TAD improve axillary staging after neoadjuvant chemotherapy, there is no long-term data about the oncologic safety of omitting ALND in |
Surgery_Schwartz_4038 | Surgery_Schwartz | of dual tracer tech-nique, retrieval of three or more SLNs, and TAD improve axillary staging after neoadjuvant chemotherapy, there is no long-term data about the oncologic safety of omitting ALND in patients who con-vert from cN1 to cN0 disease at this time.Neoadjuvant Endocrine Therapy. While initially used in elderly women who were deemed poor candidates for surgery or cytotoxic chemotherapy, neoadjuvant endocrine therapy is being increasingly evaluated in clinical trials. As clinicians have gained experience with neoadjuvant treatment strategies, it is now clear from examination of predictors of complete pathologic response that ER-positive tumors do not shrink in response to chemotherapy as readily as ER-negative tumors.320 Indeed, the pCR rate in ER-negative tumors is approximately three times that of ER-positive tumors. Fisher et al examined the results of the NSABP B-14 and B-20 trials and found that, as age increased, women obtained less benefit from chemo-therapy. They | Surgery_Schwartz. of dual tracer tech-nique, retrieval of three or more SLNs, and TAD improve axillary staging after neoadjuvant chemotherapy, there is no long-term data about the oncologic safety of omitting ALND in patients who con-vert from cN1 to cN0 disease at this time.Neoadjuvant Endocrine Therapy. While initially used in elderly women who were deemed poor candidates for surgery or cytotoxic chemotherapy, neoadjuvant endocrine therapy is being increasingly evaluated in clinical trials. As clinicians have gained experience with neoadjuvant treatment strategies, it is now clear from examination of predictors of complete pathologic response that ER-positive tumors do not shrink in response to chemotherapy as readily as ER-negative tumors.320 Indeed, the pCR rate in ER-negative tumors is approximately three times that of ER-positive tumors. Fisher et al examined the results of the NSABP B-14 and B-20 trials and found that, as age increased, women obtained less benefit from chemo-therapy. They |
Surgery_Schwartz_4039 | Surgery_Schwartz | three times that of ER-positive tumors. Fisher et al examined the results of the NSABP B-14 and B-20 trials and found that, as age increased, women obtained less benefit from chemo-therapy. They recommended that factors214 including tumor estrogen receptor concentration, nuclear grade, histologic grade, tumor type, and markers of proliferation should be considered in these patients before choosing between the use of chemotherapy and hormonal therapy. If in fact the tumor is estrogen-receptor rich, these patients may benefit more from endocrine therapy in the neoadjuvant setting than they might if they received stan-dard chemotherapy. Neoadjuvant endocrine therapy has been shown to shrink tumors, enabling breast-conserving surgery in women with hormone receptor-positive disease who otherwise would have to be treated with mastectomy, although long-term recurrence rates have not been reported.265 The IMPACT trial evaluated neoadjuvant use of tamoxifen or anastrozole or both in | Surgery_Schwartz. three times that of ER-positive tumors. Fisher et al examined the results of the NSABP B-14 and B-20 trials and found that, as age increased, women obtained less benefit from chemo-therapy. They recommended that factors214 including tumor estrogen receptor concentration, nuclear grade, histologic grade, tumor type, and markers of proliferation should be considered in these patients before choosing between the use of chemotherapy and hormonal therapy. If in fact the tumor is estrogen-receptor rich, these patients may benefit more from endocrine therapy in the neoadjuvant setting than they might if they received stan-dard chemotherapy. Neoadjuvant endocrine therapy has been shown to shrink tumors, enabling breast-conserving surgery in women with hormone receptor-positive disease who otherwise would have to be treated with mastectomy, although long-term recurrence rates have not been reported.265 The IMPACT trial evaluated neoadjuvant use of tamoxifen or anastrozole or both in |
Surgery_Schwartz_4040 | Surgery_Schwartz | otherwise would have to be treated with mastectomy, although long-term recurrence rates have not been reported.265 The IMPACT trial evaluated neoadjuvant use of tamoxifen or anastrozole or both in combination in postmenopausal women with ER-positive operable or locally advanced breast cancer.321 While there were no significant differences in objective tumor response among tamoxifen, anastrozole, or a combination of the two, in patients who were initially deemed as mastectomy candidates, only 31% had breast-conserving surgery with tamoxifen, whereas 44% underwent breast-conserving surgery with anastrozole. Invasive lobular cancers in particular have been shown to respond poorly to neoadjuvant chemotherapy and may have better response to neoadjuvant endocrine therapy.322-324 A meta-analysis evaluating the response rate and rate of breast conservation surgery with the use of neoadjuvant endocrine therapy compared to combi-nation chemotherapy was recently reported. This meta-analysis | Surgery_Schwartz. otherwise would have to be treated with mastectomy, although long-term recurrence rates have not been reported.265 The IMPACT trial evaluated neoadjuvant use of tamoxifen or anastrozole or both in combination in postmenopausal women with ER-positive operable or locally advanced breast cancer.321 While there were no significant differences in objective tumor response among tamoxifen, anastrozole, or a combination of the two, in patients who were initially deemed as mastectomy candidates, only 31% had breast-conserving surgery with tamoxifen, whereas 44% underwent breast-conserving surgery with anastrozole. Invasive lobular cancers in particular have been shown to respond poorly to neoadjuvant chemotherapy and may have better response to neoadjuvant endocrine therapy.322-324 A meta-analysis evaluating the response rate and rate of breast conservation surgery with the use of neoadjuvant endocrine therapy compared to combi-nation chemotherapy was recently reported. This meta-analysis |
Surgery_Schwartz_4041 | Surgery_Schwartz | evaluating the response rate and rate of breast conservation surgery with the use of neoadjuvant endocrine therapy compared to combi-nation chemotherapy was recently reported. This meta-analysis included nearly 3500 patients across 20 studies.325 Interestingly, aromatase inhibitors had a similar response, and breast conserva-tion rates in comparison with combination chemotherapy albeit with lower toxicity suggest that neoadjuvant endocrine therapy is an appropriate alternative in ER-positive breast cancers. However, the incidence of complete pathological response was low (<10%) with both approaches. Also, aromatase inhibitors were associated with significantly higher response and breast conservation rates compared with tamoxifen. The ALTER-NATE (Alternate Approaches for Clinical Stage II or III Estro-gen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women) trial is currently evaluating neo-adjuvant endocrine therapy with fulvestrant or anastrozole or in | Surgery_Schwartz. evaluating the response rate and rate of breast conservation surgery with the use of neoadjuvant endocrine therapy compared to combi-nation chemotherapy was recently reported. This meta-analysis included nearly 3500 patients across 20 studies.325 Interestingly, aromatase inhibitors had a similar response, and breast conserva-tion rates in comparison with combination chemotherapy albeit with lower toxicity suggest that neoadjuvant endocrine therapy is an appropriate alternative in ER-positive breast cancers. However, the incidence of complete pathological response was low (<10%) with both approaches. Also, aromatase inhibitors were associated with significantly higher response and breast conservation rates compared with tamoxifen. The ALTER-NATE (Alternate Approaches for Clinical Stage II or III Estro-gen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women) trial is currently evaluating neo-adjuvant endocrine therapy with fulvestrant or anastrozole or in |
Surgery_Schwartz_4042 | Surgery_Schwartz | II or III Estro-gen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women) trial is currently evaluating neo-adjuvant endocrine therapy with fulvestrant or anastrozole or in combination.Increasing knowledge of secondary resistance mecha-nisms to endocrine therapy and cross talk between ER and the PI3K/Akt/mTOR pathway have led to the evaluation of PI3K pathway inhibitors in combination with endocrine therapy. Post-menopausal women with ER-positive early breast cancers were treated with letrozole or letrozole in combination with everoli-mus, a mTOR inhibitor, in a randomized, phase 2 clinical trial. Clinical response and antiproliferative response, characterized by reduction in Ki67, was superior in the combination arm, sug-gesting that everolimus can increase efficacy of neoadjuvant letrozole.326 The LORLEI study is evaluating the use of taselisib, a PI3K inhibitor in combination with letrozole compared with letrozole alone. With the approval of CDK 4/6 | Surgery_Schwartz. II or III Estro-gen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women) trial is currently evaluating neo-adjuvant endocrine therapy with fulvestrant or anastrozole or in combination.Increasing knowledge of secondary resistance mecha-nisms to endocrine therapy and cross talk between ER and the PI3K/Akt/mTOR pathway have led to the evaluation of PI3K pathway inhibitors in combination with endocrine therapy. Post-menopausal women with ER-positive early breast cancers were treated with letrozole or letrozole in combination with everoli-mus, a mTOR inhibitor, in a randomized, phase 2 clinical trial. Clinical response and antiproliferative response, characterized by reduction in Ki67, was superior in the combination arm, sug-gesting that everolimus can increase efficacy of neoadjuvant letrozole.326 The LORLEI study is evaluating the use of taselisib, a PI3K inhibitor in combination with letrozole compared with letrozole alone. With the approval of CDK 4/6 |
Surgery_Schwartz_4043 | Surgery_Schwartz | efficacy of neoadjuvant letrozole.326 The LORLEI study is evaluating the use of taselisib, a PI3K inhibitor in combination with letrozole compared with letrozole alone. With the approval of CDK 4/6 inhibitors in the metastatic setting, clinical trials are evaluating the use of CDK inhibitors in combination with neoadjuvant endocrine therapy. Neoadjuvant anastrozole in combination with palbociclib, a CDK4/6 inhibitor, has been shown to significantly reduce Ki67, suggesting that CDK4/6 inhibition can increase the efficacy of neoadjuvant endocrine therapy.With the use of neoadjuvant chemotherapy or endocrine therapy, observation of the response of the intact tumor and/or nodal metastases to a specific regimen could ultimately help to define which patients will benefit from specific therapies in the adjuvant setting. In adjuvant trials the primary endpoint is typi-cally survival, whereas in neoadjuvant trials the endpoints have more often been clinical or pathologic response rates. There | Surgery_Schwartz. efficacy of neoadjuvant letrozole.326 The LORLEI study is evaluating the use of taselisib, a PI3K inhibitor in combination with letrozole compared with letrozole alone. With the approval of CDK 4/6 inhibitors in the metastatic setting, clinical trials are evaluating the use of CDK inhibitors in combination with neoadjuvant endocrine therapy. Neoadjuvant anastrozole in combination with palbociclib, a CDK4/6 inhibitor, has been shown to significantly reduce Ki67, suggesting that CDK4/6 inhibition can increase the efficacy of neoadjuvant endocrine therapy.With the use of neoadjuvant chemotherapy or endocrine therapy, observation of the response of the intact tumor and/or nodal metastases to a specific regimen could ultimately help to define which patients will benefit from specific therapies in the adjuvant setting. In adjuvant trials the primary endpoint is typi-cally survival, whereas in neoadjuvant trials the endpoints have more often been clinical or pathologic response rates. There |
Surgery_Schwartz_4044 | Surgery_Schwartz | in the adjuvant setting. In adjuvant trials the primary endpoint is typi-cally survival, whereas in neoadjuvant trials the endpoints have more often been clinical or pathologic response rates. There are a number of clinical trials underway comparing neoadjuvant chemotherapy and endocrine therapy regimens with pretreat-ment and posttreatment biopsy samples obtained from the pri-mary tumors in all of the participants. These samples are being subjected to intensive genomic and proteomic analyses that may Brunicardi_Ch17_p0541-p0612.indd 59601/03/19 5:05 PM 597THE BREASTCHAPTER 17help to define a more personalized or individualized approach to breast cancer treatment in the future.Antiestrogen TherapyTamoxifen. Within the cytosol of breast cancer cells are spe-cific proteins (receptors) that bind and transfer steroid moieties into the cell nucleus to exert specific hormonal effects.308,327-331 The most widely studied hormone receptors are the estrogen receptor and progesterone | Surgery_Schwartz. in the adjuvant setting. In adjuvant trials the primary endpoint is typi-cally survival, whereas in neoadjuvant trials the endpoints have more often been clinical or pathologic response rates. There are a number of clinical trials underway comparing neoadjuvant chemotherapy and endocrine therapy regimens with pretreat-ment and posttreatment biopsy samples obtained from the pri-mary tumors in all of the participants. These samples are being subjected to intensive genomic and proteomic analyses that may Brunicardi_Ch17_p0541-p0612.indd 59601/03/19 5:05 PM 597THE BREASTCHAPTER 17help to define a more personalized or individualized approach to breast cancer treatment in the future.Antiestrogen TherapyTamoxifen. Within the cytosol of breast cancer cells are spe-cific proteins (receptors) that bind and transfer steroid moieties into the cell nucleus to exert specific hormonal effects.308,327-331 The most widely studied hormone receptors are the estrogen receptor and progesterone |
Surgery_Schwartz_4045 | Surgery_Schwartz | that bind and transfer steroid moieties into the cell nucleus to exert specific hormonal effects.308,327-331 The most widely studied hormone receptors are the estrogen receptor and progesterone receptor. Hormone receptors are detectable in >90% of well-differentiated ductal and lobular invasive cancers. Although the receptor status may remain the same between the primary cancer and metastatic disease in the same patient in the majority of cases, there are instances where the status is changed in the metastatic focus; therefore, biopsy of newly diagnosed metastatic disease should be considered for assessment of hormone receptor and HER2 status.After binding to estrogen receptors in the cytosol, tamoxi-fen blocks the uptake of estrogen by breast tissue. Clini-cal responses to antiestrogen are evident in >60% of women with hormone receptor-positive breast cancers but in <10% of women with hormone receptor-negative breast cancers. A meta-analysis by the Early Breast Cancer Trialists’ | Surgery_Schwartz. that bind and transfer steroid moieties into the cell nucleus to exert specific hormonal effects.308,327-331 The most widely studied hormone receptors are the estrogen receptor and progesterone receptor. Hormone receptors are detectable in >90% of well-differentiated ductal and lobular invasive cancers. Although the receptor status may remain the same between the primary cancer and metastatic disease in the same patient in the majority of cases, there are instances where the status is changed in the metastatic focus; therefore, biopsy of newly diagnosed metastatic disease should be considered for assessment of hormone receptor and HER2 status.After binding to estrogen receptors in the cytosol, tamoxi-fen blocks the uptake of estrogen by breast tissue. Clini-cal responses to antiestrogen are evident in >60% of women with hormone receptor-positive breast cancers but in <10% of women with hormone receptor-negative breast cancers. A meta-analysis by the Early Breast Cancer Trialists’ |
Surgery_Schwartz_4046 | Surgery_Schwartz | are evident in >60% of women with hormone receptor-positive breast cancers but in <10% of women with hormone receptor-negative breast cancers. A meta-analysis by the Early Breast Cancer Trialists’ Collabora-tive Group showed that adjuvant therapy with tamoxifen for 5 years reduced breast cancer mortality by about a third through the first 15 years of follow-up.14 This mortality benefit contin-ues to be statistically significant in the second and third 5-year periods (i.e., years 5–9 and 10–15) when the patients are no longer receiving endocrine treatment—the so-called carry-over effect. The analysis also showed a 39% reduction in the risk of cancer in the contralateral breast. The antiestrogens do have defined toxicity, including bone pain, hot flashes, nausea, vom-iting, and fluid retention. Thrombotic events occur in <3% of treated women. Cataract surgery is more frequently performed in patients receiving tamoxifen. The Stockholm trial showed that 5 years of tamoxifen was associated | Surgery_Schwartz. are evident in >60% of women with hormone receptor-positive breast cancers but in <10% of women with hormone receptor-negative breast cancers. A meta-analysis by the Early Breast Cancer Trialists’ Collabora-tive Group showed that adjuvant therapy with tamoxifen for 5 years reduced breast cancer mortality by about a third through the first 15 years of follow-up.14 This mortality benefit contin-ues to be statistically significant in the second and third 5-year periods (i.e., years 5–9 and 10–15) when the patients are no longer receiving endocrine treatment—the so-called carry-over effect. The analysis also showed a 39% reduction in the risk of cancer in the contralateral breast. The antiestrogens do have defined toxicity, including bone pain, hot flashes, nausea, vom-iting, and fluid retention. Thrombotic events occur in <3% of treated women. Cataract surgery is more frequently performed in patients receiving tamoxifen. The Stockholm trial showed that 5 years of tamoxifen was associated |
Surgery_Schwartz_4047 | Surgery_Schwartz | Thrombotic events occur in <3% of treated women. Cataract surgery is more frequently performed in patients receiving tamoxifen. The Stockholm trial showed that 5 years of tamoxifen was associated with a significant reduction in locoregional recurrences and distant metastasis in postmenopausal women with ER-positive breast cancer.332 However, an increase in endometrial cancers was observed with long-term tamoxifen use. The NSABP B14 trial evaluated 10 years of tamoxifen compared to 5 years.333 However, the study was terminated based on interim analyses indicating no addi-tional benefit from tamoxifen beyond 5 years. The ATLAS trial also evaluated the use of tamoxifen for 5 years vs. 10 years in nearly 13,000 women across the world. This study showed that continuing tamoxifen for 10 years vs. 5 years produced a significant reduction in recurrence and mortality.334 Interestingly, the benefit was not seen in the second 5 years (i.e., years 5–9) while the patients were on treatment, but | Surgery_Schwartz. Thrombotic events occur in <3% of treated women. Cataract surgery is more frequently performed in patients receiving tamoxifen. The Stockholm trial showed that 5 years of tamoxifen was associated with a significant reduction in locoregional recurrences and distant metastasis in postmenopausal women with ER-positive breast cancer.332 However, an increase in endometrial cancers was observed with long-term tamoxifen use. The NSABP B14 trial evaluated 10 years of tamoxifen compared to 5 years.333 However, the study was terminated based on interim analyses indicating no addi-tional benefit from tamoxifen beyond 5 years. The ATLAS trial also evaluated the use of tamoxifen for 5 years vs. 10 years in nearly 13,000 women across the world. This study showed that continuing tamoxifen for 10 years vs. 5 years produced a significant reduction in recurrence and mortality.334 Interestingly, the benefit was not seen in the second 5 years (i.e., years 5–9) while the patients were on treatment, but |
Surgery_Schwartz_4048 | Surgery_Schwartz | 5 years produced a significant reduction in recurrence and mortality.334 Interestingly, the benefit was not seen in the second 5 years (i.e., years 5–9) while the patients were on treatment, but it was seen from years 10 to 15. One reason the NSABP B14 study was led to conclude that 10 years of tamoxifen was not beneficial was that the follow-up time was shorter. Results of the ATLAS study were also corroborated by the aTTom study. Similarly, extended adjuvant therapy with letrozole after 5 years of tamoxifen was shown to improve disease-free survival without improvement in overall survival except in node-positive patients.335Tamoxifen therapy is also considered for women with DCIS that is found to be ER-positive. The goals of such ther-apy are to decrease the risk of an ipsilateral recurrence after breast conservation therapy for DCIS and to decrease the risk of a primary invasive breast cancer or a contralateral breast cancer event. Consequently, tamoxifen is not recommended for | Surgery_Schwartz. 5 years produced a significant reduction in recurrence and mortality.334 Interestingly, the benefit was not seen in the second 5 years (i.e., years 5–9) while the patients were on treatment, but it was seen from years 10 to 15. One reason the NSABP B14 study was led to conclude that 10 years of tamoxifen was not beneficial was that the follow-up time was shorter. Results of the ATLAS study were also corroborated by the aTTom study. Similarly, extended adjuvant therapy with letrozole after 5 years of tamoxifen was shown to improve disease-free survival without improvement in overall survival except in node-positive patients.335Tamoxifen therapy is also considered for women with DCIS that is found to be ER-positive. The goals of such ther-apy are to decrease the risk of an ipsilateral recurrence after breast conservation therapy for DCIS and to decrease the risk of a primary invasive breast cancer or a contralateral breast cancer event. Consequently, tamoxifen is not recommended for |
Surgery_Schwartz_4049 | Surgery_Schwartz | after breast conservation therapy for DCIS and to decrease the risk of a primary invasive breast cancer or a contralateral breast cancer event. Consequently, tamoxifen is not recommended for patients who have had bilateral mastectomies with ER-positive DCIS. With the use of aromatase inhibitors in postmenopausal women, use of adjuvant tamoxifen has increasingly been limited to premenopausal women.Aromatase Inhibitors. In postmenopausal women, aromatase inhibitors are now considered first-line therapy in the adjuvant setting. Currently, three third-generation aromatase inhibitors are approved for clinical use: the reversible nonsteroidal inhibitors anastrozole and letrozole and the irreversible steroidal inhibitor exemestane. While all the aromatase inhibitors have been shown to have similar efficacy with a similar spectrum of adverse effects, the Early Breast Cancer Trialists’ Collaborative Group meta-analyses of 31,920 postmenopausal women with ER-positive early breast cancers | Surgery_Schwartz. after breast conservation therapy for DCIS and to decrease the risk of a primary invasive breast cancer or a contralateral breast cancer event. Consequently, tamoxifen is not recommended for patients who have had bilateral mastectomies with ER-positive DCIS. With the use of aromatase inhibitors in postmenopausal women, use of adjuvant tamoxifen has increasingly been limited to premenopausal women.Aromatase Inhibitors. In postmenopausal women, aromatase inhibitors are now considered first-line therapy in the adjuvant setting. Currently, three third-generation aromatase inhibitors are approved for clinical use: the reversible nonsteroidal inhibitors anastrozole and letrozole and the irreversible steroidal inhibitor exemestane. While all the aromatase inhibitors have been shown to have similar efficacy with a similar spectrum of adverse effects, the Early Breast Cancer Trialists’ Collaborative Group meta-analyses of 31,920 postmenopausal women with ER-positive early breast cancers |
Surgery_Schwartz_4050 | Surgery_Schwartz | similar efficacy with a similar spectrum of adverse effects, the Early Breast Cancer Trialists’ Collaborative Group meta-analyses of 31,920 postmenopausal women with ER-positive early breast cancers treated with tamoxifen or aroma-tase inhibitors demonstrated that 5 years of aromatase inhibitors reduced the rate of recurrence by 30% and 10-year breast cancer mortality by about 15% compared to 5 years of tamoxifen.336-339 The NSABP B42 study evaluated whether an additional 5 years of letrozole improved disease-free survival in postmenopausal women who have completed 5 years of tamoxifen or an aromatase inhibitor. After a median follow-up of 6.9 years, while extended letrozole significantly improved breast cancer-free interval, no improvement in disease-free survival, the primary endpoint, was observed. Recently, the results of the MA-17R study, designed to assess the efficacy of adjuvant letrozole for 10 years, were reported.340 Similar to NSABP B42, extended letrozole improved | Surgery_Schwartz. similar efficacy with a similar spectrum of adverse effects, the Early Breast Cancer Trialists’ Collaborative Group meta-analyses of 31,920 postmenopausal women with ER-positive early breast cancers treated with tamoxifen or aroma-tase inhibitors demonstrated that 5 years of aromatase inhibitors reduced the rate of recurrence by 30% and 10-year breast cancer mortality by about 15% compared to 5 years of tamoxifen.336-339 The NSABP B42 study evaluated whether an additional 5 years of letrozole improved disease-free survival in postmenopausal women who have completed 5 years of tamoxifen or an aromatase inhibitor. After a median follow-up of 6.9 years, while extended letrozole significantly improved breast cancer-free interval, no improvement in disease-free survival, the primary endpoint, was observed. Recently, the results of the MA-17R study, designed to assess the efficacy of adjuvant letrozole for 10 years, were reported.340 Similar to NSABP B42, extended letrozole improved |
Surgery_Schwartz_4051 | Surgery_Schwartz | was observed. Recently, the results of the MA-17R study, designed to assess the efficacy of adjuvant letrozole for 10 years, were reported.340 Similar to NSABP B42, extended letrozole improved disease-free survival without significant improvement in overall survival. Patients who are node-positive, have received adjuvant chemotherapy, with prior receipt of tamoxifen are likely to ben-efit from long-term use of an aromatase inhibitor.The aromatase inhibitors are less likely than tamoxifen to cause endometrial cancer but do lead to changes in bone mineral density that may result in osteoporosis and an increased rate of fractures in postmenopausal women. The risk of osteoporosis can be averted by treatment with bisphosphonates. Joint pains are a side effect that affects a significant number of patients. Node-negative and node-positive breast cancer patients whose tumors express hormone receptors should be considered for endocrine therapy in the adjuvant setting. Women with hormone | Surgery_Schwartz. was observed. Recently, the results of the MA-17R study, designed to assess the efficacy of adjuvant letrozole for 10 years, were reported.340 Similar to NSABP B42, extended letrozole improved disease-free survival without significant improvement in overall survival. Patients who are node-positive, have received adjuvant chemotherapy, with prior receipt of tamoxifen are likely to ben-efit from long-term use of an aromatase inhibitor.The aromatase inhibitors are less likely than tamoxifen to cause endometrial cancer but do lead to changes in bone mineral density that may result in osteoporosis and an increased rate of fractures in postmenopausal women. The risk of osteoporosis can be averted by treatment with bisphosphonates. Joint pains are a side effect that affects a significant number of patients. Node-negative and node-positive breast cancer patients whose tumors express hormone receptors should be considered for endocrine therapy in the adjuvant setting. Women with hormone |
Surgery_Schwartz_4052 | Surgery_Schwartz | of patients. Node-negative and node-positive breast cancer patients whose tumors express hormone receptors should be considered for endocrine therapy in the adjuvant setting. Women with hormone receptor–positive cancers achieve significant reduction in risk of recurrence of breast cancer and mortality from breast cancer through the use of endocrine therapies.For postmenopausal women with ER-positive, HER2-negative, metastatic breast cancer, available endocrine thera-pies include nonsteroidal aromatase inhibitors (anastrozole and letrozole); steroidal aromatase inhibitors (exemestane); serum ER modulators (tamoxifen or toremifene); ER down-regulators (fulvestrant); progestin (megestrol acetate); androgens (fluoxymesterone); and high-dose estrogen (ethinyl estradiol). A third generation nonsteroidal aromatase inhibitor or palbo-ciclib, the CDK 4/6 inhibitor, in combination with letrozole may be considered as a treatment option for first-line therapy. Activation of CDK4/CDK6 cell cycle | Surgery_Schwartz. of patients. Node-negative and node-positive breast cancer patients whose tumors express hormone receptors should be considered for endocrine therapy in the adjuvant setting. Women with hormone receptor–positive cancers achieve significant reduction in risk of recurrence of breast cancer and mortality from breast cancer through the use of endocrine therapies.For postmenopausal women with ER-positive, HER2-negative, metastatic breast cancer, available endocrine thera-pies include nonsteroidal aromatase inhibitors (anastrozole and letrozole); steroidal aromatase inhibitors (exemestane); serum ER modulators (tamoxifen or toremifene); ER down-regulators (fulvestrant); progestin (megestrol acetate); androgens (fluoxymesterone); and high-dose estrogen (ethinyl estradiol). A third generation nonsteroidal aromatase inhibitor or palbo-ciclib, the CDK 4/6 inhibitor, in combination with letrozole may be considered as a treatment option for first-line therapy. Activation of CDK4/CDK6 cell cycle |
Surgery_Schwartz_4053 | Surgery_Schwartz | aromatase inhibitor or palbo-ciclib, the CDK 4/6 inhibitor, in combination with letrozole may be considered as a treatment option for first-line therapy. Activation of CDK4/CDK6 cell cycle signaling axis has been implicated in mediating endocrine resistance. Consequently, PALOMA-1 evaluated the safety and efficacy of palbociclib in combination with letrozole vs. letrozole alone as first-line treat-ment for patients with ER-positive, HER2-negative advanced breast cancer. Median progression-free survival (PFS) was doubled with the combination compared to letrozole alone (20.2 months vs. 10.2 months for the letrozole).341 Based on this, the FDA approved palbociclib in combination with letrozole for the treatment of postmenopausal women with ER-positive, HER2-negative advanced breast cancer as initial treatment. The Brunicardi_Ch17_p0541-p0612.indd 59701/03/19 5:05 PM 598SPECIFIC CONSIDERATIONSPART IIbenefit of palbociclib in combination with letrozole was sub-sequently confirmed in | Surgery_Schwartz. aromatase inhibitor or palbo-ciclib, the CDK 4/6 inhibitor, in combination with letrozole may be considered as a treatment option for first-line therapy. Activation of CDK4/CDK6 cell cycle signaling axis has been implicated in mediating endocrine resistance. Consequently, PALOMA-1 evaluated the safety and efficacy of palbociclib in combination with letrozole vs. letrozole alone as first-line treat-ment for patients with ER-positive, HER2-negative advanced breast cancer. Median progression-free survival (PFS) was doubled with the combination compared to letrozole alone (20.2 months vs. 10.2 months for the letrozole).341 Based on this, the FDA approved palbociclib in combination with letrozole for the treatment of postmenopausal women with ER-positive, HER2-negative advanced breast cancer as initial treatment. The Brunicardi_Ch17_p0541-p0612.indd 59701/03/19 5:05 PM 598SPECIFIC CONSIDERATIONSPART IIbenefit of palbociclib in combination with letrozole was sub-sequently confirmed in |
Surgery_Schwartz_4054 | Surgery_Schwartz | as initial treatment. The Brunicardi_Ch17_p0541-p0612.indd 59701/03/19 5:05 PM 598SPECIFIC CONSIDERATIONSPART IIbenefit of palbociclib in combination with letrozole was sub-sequently confirmed in a phase 3 trial (PFS 24.8 months vs. 14.5 months for letrozole).342 Two additional CDK4/6 inhibitors, ribociclib and abemaciclib, have been approved for use in com-bination with endocrine therapy for patients with hormone receptor–positive advanced breast cancer.On the other hand, PALOMA-3 compared the combina-tion of palbociclib and fulvestrant to fulvestrant alone in preor postmenopausal ER-positive, HER2-negative metastatic breast cancer patients, whose disease progressed on prior endocrine therapy. Premenopausal women also received the GNRH ago-nist, goserelin. The median PFS was 9.2 months for the combi-nation compared to 3.8 months with fulvestrant alone.343 Thus, fulvestrant with palbociclib is a potential option for women with metastatic breast cancer who have progressed on prior | Surgery_Schwartz. as initial treatment. The Brunicardi_Ch17_p0541-p0612.indd 59701/03/19 5:05 PM 598SPECIFIC CONSIDERATIONSPART IIbenefit of palbociclib in combination with letrozole was sub-sequently confirmed in a phase 3 trial (PFS 24.8 months vs. 14.5 months for letrozole).342 Two additional CDK4/6 inhibitors, ribociclib and abemaciclib, have been approved for use in com-bination with endocrine therapy for patients with hormone receptor–positive advanced breast cancer.On the other hand, PALOMA-3 compared the combina-tion of palbociclib and fulvestrant to fulvestrant alone in preor postmenopausal ER-positive, HER2-negative metastatic breast cancer patients, whose disease progressed on prior endocrine therapy. Premenopausal women also received the GNRH ago-nist, goserelin. The median PFS was 9.2 months for the combi-nation compared to 3.8 months with fulvestrant alone.343 Thus, fulvestrant with palbociclib is a potential option for women with metastatic breast cancer who have progressed on prior |
Surgery_Schwartz_4055 | Surgery_Schwartz | for the combi-nation compared to 3.8 months with fulvestrant alone.343 Thus, fulvestrant with palbociclib is a potential option for women with metastatic breast cancer who have progressed on prior endo-crine therapy. Additionally, abemaciclib in combination with fulvestrant or as single agent is approved for use in ER-posi-tive advanced breast cancers previously treated with endocrine therapy.In premenopausal women with stage IV ER-positive breast cancer without previous exposure to endocrine therapy, initial treatment with tamoxifen or ovarian suppression/ablation plus aromatase inhibitor with or without CDK4/6 inhibitors are reasonable options.Activation of the PI3K/mammalian target of rapamycin (mTOR) signal transduction pathway has also been implicated in secondary resistance to estrogen targeting. BOLERO-2 eval-uated the use of exemestane in combination with everolimus in postmenopausal women with ER-positive tumors who had progressed or recurred on a nonsteroidal aromatase | Surgery_Schwartz. for the combi-nation compared to 3.8 months with fulvestrant alone.343 Thus, fulvestrant with palbociclib is a potential option for women with metastatic breast cancer who have progressed on prior endo-crine therapy. Additionally, abemaciclib in combination with fulvestrant or as single agent is approved for use in ER-posi-tive advanced breast cancers previously treated with endocrine therapy.In premenopausal women with stage IV ER-positive breast cancer without previous exposure to endocrine therapy, initial treatment with tamoxifen or ovarian suppression/ablation plus aromatase inhibitor with or without CDK4/6 inhibitors are reasonable options.Activation of the PI3K/mammalian target of rapamycin (mTOR) signal transduction pathway has also been implicated in secondary resistance to estrogen targeting. BOLERO-2 eval-uated the use of exemestane in combination with everolimus in postmenopausal women with ER-positive tumors who had progressed or recurred on a nonsteroidal aromatase |
Surgery_Schwartz_4056 | Surgery_Schwartz | estrogen targeting. BOLERO-2 eval-uated the use of exemestane in combination with everolimus in postmenopausal women with ER-positive tumors who had progressed or recurred on a nonsteroidal aromatase inhibitor.344 An improvement in PFS was observed with combination com-pared to exemestane alone (11 vs. 4.1 months) leading to FDA approval. Similar improvement in PFS was observed with a combination of tamoxifen and everolimus.345 However, a phase 3 trial of letrozole in combination with temsirolimus, an mTOR inhibitor, did not show any improvement in PFS in aromatase inhibitor–naive metastatic postmenopausal women.346 Trials evaluating the adjuvant use of mTOR inhibitors and CDK 4/6 inhibitors are currently in progress.Women whose tumors respond to an endocrine therapy with either shrinkage of their breast cancer (objective response) or long-term stabilization of disease (stable disease) are con-sidered to represent “clinical benefit” and should receive addi-tional endocrine therapy at | Surgery_Schwartz. estrogen targeting. BOLERO-2 eval-uated the use of exemestane in combination with everolimus in postmenopausal women with ER-positive tumors who had progressed or recurred on a nonsteroidal aromatase inhibitor.344 An improvement in PFS was observed with combination com-pared to exemestane alone (11 vs. 4.1 months) leading to FDA approval. Similar improvement in PFS was observed with a combination of tamoxifen and everolimus.345 However, a phase 3 trial of letrozole in combination with temsirolimus, an mTOR inhibitor, did not show any improvement in PFS in aromatase inhibitor–naive metastatic postmenopausal women.346 Trials evaluating the adjuvant use of mTOR inhibitors and CDK 4/6 inhibitors are currently in progress.Women whose tumors respond to an endocrine therapy with either shrinkage of their breast cancer (objective response) or long-term stabilization of disease (stable disease) are con-sidered to represent “clinical benefit” and should receive addi-tional endocrine therapy at |
Surgery_Schwartz_4057 | Surgery_Schwartz | of their breast cancer (objective response) or long-term stabilization of disease (stable disease) are con-sidered to represent “clinical benefit” and should receive addi-tional endocrine therapy at the time of progression because their chances of a further response remain high.294-296 Patients whose tumors progress de novo on an endocrine agent have a low rate of clinical benefit (<20%) to subsequent endocrine therapy; the choice of endocrine or chemotherapy should be considered based on the disease site and extent as well as the patient’s general condition and treatment preference.294The adjuvant use of aromatase inhibitors and recent advances in tumor genome sequencing technologies have enabled the identification of secondary ESR1 mutations.347,348 These mutations, typically present in the ligand binding domains, lead to ligand-independent activation of the receptor, mediate resistance to aromatase inhibitors, and are associated with shorter survival.349 Reported incidence of these | Surgery_Schwartz. of their breast cancer (objective response) or long-term stabilization of disease (stable disease) are con-sidered to represent “clinical benefit” and should receive addi-tional endocrine therapy at the time of progression because their chances of a further response remain high.294-296 Patients whose tumors progress de novo on an endocrine agent have a low rate of clinical benefit (<20%) to subsequent endocrine therapy; the choice of endocrine or chemotherapy should be considered based on the disease site and extent as well as the patient’s general condition and treatment preference.294The adjuvant use of aromatase inhibitors and recent advances in tumor genome sequencing technologies have enabled the identification of secondary ESR1 mutations.347,348 These mutations, typically present in the ligand binding domains, lead to ligand-independent activation of the receptor, mediate resistance to aromatase inhibitors, and are associated with shorter survival.349 Reported incidence of these |
Surgery_Schwartz_4058 | Surgery_Schwartz | the ligand binding domains, lead to ligand-independent activation of the receptor, mediate resistance to aromatase inhibitors, and are associated with shorter survival.349 Reported incidence of these mutations are variable (20%–30%) based on prior exposure to aroma-tase inhibitors and are uncommon in primary breast cancers. Clinical trials evaluating novel selective estrogen receptor degraders with potential activity against these mutations are in progress.Ablative Endocrine TherapyIn the past, adrenalectomy and/or hypophysectomy were the pri-mary endocrine modalities used to treat metastatic breast cancer, but today these approaches are seldom used. In women who are premenopausal at diagnosis, ovarian ablation can be accomplished by oophorectomy or ovarian radiation. Ovarian suppression can be accomplished by the use of gonadotrophin-hormone releasing hormone agonists, such as goserelin or leuprolide. Evaluation of the combination of goserelin with tamoxifen vs. | Surgery_Schwartz. the ligand binding domains, lead to ligand-independent activation of the receptor, mediate resistance to aromatase inhibitors, and are associated with shorter survival.349 Reported incidence of these mutations are variable (20%–30%) based on prior exposure to aroma-tase inhibitors and are uncommon in primary breast cancers. Clinical trials evaluating novel selective estrogen receptor degraders with potential activity against these mutations are in progress.Ablative Endocrine TherapyIn the past, adrenalectomy and/or hypophysectomy were the pri-mary endocrine modalities used to treat metastatic breast cancer, but today these approaches are seldom used. In women who are premenopausal at diagnosis, ovarian ablation can be accomplished by oophorectomy or ovarian radiation. Ovarian suppression can be accomplished by the use of gonadotrophin-hormone releasing hormone agonists, such as goserelin or leuprolide. Evaluation of the combination of goserelin with tamoxifen vs. |
Surgery_Schwartz_4059 | Surgery_Schwartz | Ovarian suppression can be accomplished by the use of gonadotrophin-hormone releasing hormone agonists, such as goserelin or leuprolide. Evaluation of the combination of goserelin with tamoxifen vs. cyclophospha-mide/methotrexate/fluorouracil chemotherapy in premenopausal ER-positive early-stage breast cancers showed that relapse-free survival was superior with endocrine therapy combination, with a similar trend in overall survival.350 Data from the SOFT and TEXT trials on adjuvant endocrine therapy show that exemes-tane plus ovarian suppression significantly reduces recurrences as compared with tamoxifen plus ovarian suppression.351,352 In these trials, ovarian suppression was achieved with the use of the gonadotropin-releasing hormone agonist triptorelin, oopho-rectomy, or ovarian irradiation. The disease-free survival was 89% in the tamoxifen plus ovarian suppression group, while it was 93% in exemestane plus ovarian suppression group; how-ever, there was no significant | Surgery_Schwartz. Ovarian suppression can be accomplished by the use of gonadotrophin-hormone releasing hormone agonists, such as goserelin or leuprolide. Evaluation of the combination of goserelin with tamoxifen vs. cyclophospha-mide/methotrexate/fluorouracil chemotherapy in premenopausal ER-positive early-stage breast cancers showed that relapse-free survival was superior with endocrine therapy combination, with a similar trend in overall survival.350 Data from the SOFT and TEXT trials on adjuvant endocrine therapy show that exemes-tane plus ovarian suppression significantly reduces recurrences as compared with tamoxifen plus ovarian suppression.351,352 In these trials, ovarian suppression was achieved with the use of the gonadotropin-releasing hormone agonist triptorelin, oopho-rectomy, or ovarian irradiation. The disease-free survival was 89% in the tamoxifen plus ovarian suppression group, while it was 93% in exemestane plus ovarian suppression group; how-ever, there was no significant |
Surgery_Schwartz_4060 | Surgery_Schwartz | irradiation. The disease-free survival was 89% in the tamoxifen plus ovarian suppression group, while it was 93% in exemestane plus ovarian suppression group; how-ever, there was no significant differences in overall survival. In the SOFT trial, while tamoxifen plus ovarian suppression was not superior to tamoxifen alone in terms of disease-free survival, improved outcomes were observed in ovarian suppression in women with a high risk of recurrence. In women who received no adjuvant chemotherapy, no meaningful benefit was obtained with ovarian suppression. Thus, ovarian suppression in combi-nation with an aromatase inhibitor can be considered in select premenopausal women with high-risk features (age <40 years, positive lymph nodes) who warranted adjuvant chemotherapy.Anti-HER2 TherapyThe determination of tumor HER-2 expression or gene ampli-fication for all newly diagnosed patients with breast cancer is now recommended.353-356 It is used to assist in the selection of adjuvant | Surgery_Schwartz. irradiation. The disease-free survival was 89% in the tamoxifen plus ovarian suppression group, while it was 93% in exemestane plus ovarian suppression group; how-ever, there was no significant differences in overall survival. In the SOFT trial, while tamoxifen plus ovarian suppression was not superior to tamoxifen alone in terms of disease-free survival, improved outcomes were observed in ovarian suppression in women with a high risk of recurrence. In women who received no adjuvant chemotherapy, no meaningful benefit was obtained with ovarian suppression. Thus, ovarian suppression in combi-nation with an aromatase inhibitor can be considered in select premenopausal women with high-risk features (age <40 years, positive lymph nodes) who warranted adjuvant chemotherapy.Anti-HER2 TherapyThe determination of tumor HER-2 expression or gene ampli-fication for all newly diagnosed patients with breast cancer is now recommended.353-356 It is used to assist in the selection of adjuvant |
Surgery_Schwartz_4061 | Surgery_Schwartz | determination of tumor HER-2 expression or gene ampli-fication for all newly diagnosed patients with breast cancer is now recommended.353-356 It is used to assist in the selection of adjuvant chemotherapy in both node-negative and node-positive patients. Trastuzumab was initially approved for the treatment of HER2/neu-positive breast cancer in patients with metastatic disease. Once efficacy was demonstrated for patients with metastatic disease, the NSABP and the North Central Cancer Treatment Group conducted phase 3 trials that evaluated the impact of adjuvant trastuzumab therapy in patients with early-stage breast cancer. After approval from the FDA, these groups amended their adjuvant trastuzumab trials (B-31 and N9831, respectively), to provide for a joint efficacy analysis. The first joint interim efficacy analysis demonstrated an improvement in 3-year disease-free survival from 75% in the control arm to 87% in the trastuzumab arm (hazard ratio = 0.48, P <.0001). There was an | Surgery_Schwartz. determination of tumor HER-2 expression or gene ampli-fication for all newly diagnosed patients with breast cancer is now recommended.353-356 It is used to assist in the selection of adjuvant chemotherapy in both node-negative and node-positive patients. Trastuzumab was initially approved for the treatment of HER2/neu-positive breast cancer in patients with metastatic disease. Once efficacy was demonstrated for patients with metastatic disease, the NSABP and the North Central Cancer Treatment Group conducted phase 3 trials that evaluated the impact of adjuvant trastuzumab therapy in patients with early-stage breast cancer. After approval from the FDA, these groups amended their adjuvant trastuzumab trials (B-31 and N9831, respectively), to provide for a joint efficacy analysis. The first joint interim efficacy analysis demonstrated an improvement in 3-year disease-free survival from 75% in the control arm to 87% in the trastuzumab arm (hazard ratio = 0.48, P <.0001). There was an |
Surgery_Schwartz_4062 | Surgery_Schwartz | joint interim efficacy analysis demonstrated an improvement in 3-year disease-free survival from 75% in the control arm to 87% in the trastuzumab arm (hazard ratio = 0.48, P <.0001). There was an accompanying 33% reduction in mortality in the patients who received trastuzumab (hazard ratio = 0.67, P = 0.015). The magnitude of reduction in hazard for disease-free survival events crossed prespecified early reporting boundaries, so the data-monitoring committees for both groups recommended that randomized accrual to the trials be ended, and the results were subsequently published.181While anthracycline-based adjuvant chemotherapy was considered preferable in HER2-positive breast cancer, the BCIRG 006 compared the use of anthracycline with taxane and trastuzumab (AC-TH) versus taxane, carboplatin chemotherapy with trastuzumab (TCH).182 With 10 years of follow-up, no statistical significance with regard to disease-free and overall Brunicardi_Ch17_p0541-p0612.indd 59801/03/19 5:05 PM | Surgery_Schwartz. joint interim efficacy analysis demonstrated an improvement in 3-year disease-free survival from 75% in the control arm to 87% in the trastuzumab arm (hazard ratio = 0.48, P <.0001). There was an accompanying 33% reduction in mortality in the patients who received trastuzumab (hazard ratio = 0.67, P = 0.015). The magnitude of reduction in hazard for disease-free survival events crossed prespecified early reporting boundaries, so the data-monitoring committees for both groups recommended that randomized accrual to the trials be ended, and the results were subsequently published.181While anthracycline-based adjuvant chemotherapy was considered preferable in HER2-positive breast cancer, the BCIRG 006 compared the use of anthracycline with taxane and trastuzumab (AC-TH) versus taxane, carboplatin chemotherapy with trastuzumab (TCH).182 With 10 years of follow-up, no statistical significance with regard to disease-free and overall Brunicardi_Ch17_p0541-p0612.indd 59801/03/19 5:05 PM |
Surgery_Schwartz_4063 | Surgery_Schwartz | chemotherapy with trastuzumab (TCH).182 With 10 years of follow-up, no statistical significance with regard to disease-free and overall Brunicardi_Ch17_p0541-p0612.indd 59801/03/19 5:05 PM 599THE BREASTCHAPTER 17survival was observed for anthracycline-based chemotherapy. While anthracycline chemotherapy was numerically superior, this was accompanied by an increase in the incidence of leu-kemia and congestive heart failure. A year of adjuvant trastu-zumab is considered standard of care. Two years of adjuvant trastuzumab has been shown to be more effective, although it is associated with more toxicity than 1 year of trastuzumab.357 On the other hand, the PHARE trial examined 6 months vs. stan-dard 12 months of trastuzumab. After 3.5 years of follow-up, the study failed to demonstrate that 6 months was noninferior com-pared to the standard therapy.358 Patients with HER2-positive tumors benefit if trastuzumab is added to taxane chemotherapy. Because of overlapping cardiotoxicities, | Surgery_Schwartz. chemotherapy with trastuzumab (TCH).182 With 10 years of follow-up, no statistical significance with regard to disease-free and overall Brunicardi_Ch17_p0541-p0612.indd 59801/03/19 5:05 PM 599THE BREASTCHAPTER 17survival was observed for anthracycline-based chemotherapy. While anthracycline chemotherapy was numerically superior, this was accompanied by an increase in the incidence of leu-kemia and congestive heart failure. A year of adjuvant trastu-zumab is considered standard of care. Two years of adjuvant trastuzumab has been shown to be more effective, although it is associated with more toxicity than 1 year of trastuzumab.357 On the other hand, the PHARE trial examined 6 months vs. stan-dard 12 months of trastuzumab. After 3.5 years of follow-up, the study failed to demonstrate that 6 months was noninferior com-pared to the standard therapy.358 Patients with HER2-positive tumors benefit if trastuzumab is added to taxane chemotherapy. Because of overlapping cardiotoxicities, |
Surgery_Schwartz_4064 | Surgery_Schwartz | that 6 months was noninferior com-pared to the standard therapy.358 Patients with HER2-positive tumors benefit if trastuzumab is added to taxane chemotherapy. Because of overlapping cardiotoxicities, trastuzumab is not usu-ally given concurrently with anthracyclines.Buzdar and colleagues reported the results of a random-ized neoadjuvant trial of trastuzumab in combination with sequential paclitaxel followed by FEC-75 (5-fluorouracil, epi-rubicin, cyclophosphamide) vs. the same chemotherapy regimen without trastuzumab in 42 women with early-stage operable breast cancer. The pathologic complete response rates in this trial increased from 25% to 66.7% when chemotherapy was given concurrently with trastuzumab.301 A subsequent report that included additional patients treated with concurrent chemo-therapy and trastuzumab further confirmed the high pathologic complete response rates and continued to show that cardiac function was preserved.302While novel agents have been approved for the | Surgery_Schwartz. that 6 months was noninferior com-pared to the standard therapy.358 Patients with HER2-positive tumors benefit if trastuzumab is added to taxane chemotherapy. Because of overlapping cardiotoxicities, trastuzumab is not usu-ally given concurrently with anthracyclines.Buzdar and colleagues reported the results of a random-ized neoadjuvant trial of trastuzumab in combination with sequential paclitaxel followed by FEC-75 (5-fluorouracil, epi-rubicin, cyclophosphamide) vs. the same chemotherapy regimen without trastuzumab in 42 women with early-stage operable breast cancer. The pathologic complete response rates in this trial increased from 25% to 66.7% when chemotherapy was given concurrently with trastuzumab.301 A subsequent report that included additional patients treated with concurrent chemo-therapy and trastuzumab further confirmed the high pathologic complete response rates and continued to show that cardiac function was preserved.302While novel agents have been approved for the |
Surgery_Schwartz_4065 | Surgery_Schwartz | chemo-therapy and trastuzumab further confirmed the high pathologic complete response rates and continued to show that cardiac function was preserved.302While novel agents have been approved for the treatment of women with metastatic HER2-positive breast cancers, cur-rently trastuzumab is the only HER2-targeted agent approved for use in the adjuvant setting. Lapatinib is a dual tyrosine kinase inhibitor that targets both HER2 and EGFR. It was approved for use with capecitabine in patients with HER2-positive meta-static disease. Adjuvant lapatinib was shown to be inferior to trastuzumab, and the combination of lapatinib with trastuzumab did yield a significant improvement in disease-free survival compared to trastuzumab alone. Ado-trastuzumab emtansine (T-DM1) is approved for HER2-positive metastatic breast cancer patients who have previously received trastuzumab and a taxane either separately or in combination. T-DM1 is an antibody drug conjugate that incorporates the HER2 targeted | Surgery_Schwartz. chemo-therapy and trastuzumab further confirmed the high pathologic complete response rates and continued to show that cardiac function was preserved.302While novel agents have been approved for the treatment of women with metastatic HER2-positive breast cancers, cur-rently trastuzumab is the only HER2-targeted agent approved for use in the adjuvant setting. Lapatinib is a dual tyrosine kinase inhibitor that targets both HER2 and EGFR. It was approved for use with capecitabine in patients with HER2-positive meta-static disease. Adjuvant lapatinib was shown to be inferior to trastuzumab, and the combination of lapatinib with trastuzumab did yield a significant improvement in disease-free survival compared to trastuzumab alone. Ado-trastuzumab emtansine (T-DM1) is approved for HER2-positive metastatic breast cancer patients who have previously received trastuzumab and a taxane either separately or in combination. T-DM1 is an antibody drug conjugate that incorporates the HER2 targeted |
Surgery_Schwartz_4066 | Surgery_Schwartz | metastatic breast cancer patients who have previously received trastuzumab and a taxane either separately or in combination. T-DM1 is an antibody drug conjugate that incorporates the HER2 targeted activity of trastuzumab with the cytotoxic activity of DM1, a microtubule inhibitory agent leading to apoptosis.359Pertuzumab is a humanized monoclonal antibody that binds at a different epitope of the HER2 extracellular domain (subdomain II) and prevents dimerization of HER2 with other members of the family, primarily HER3. In the metastatic setting, it is approved in combination with trastuzumab and docetaxel for patients with metastatic HER2-positive breast cancer who have not received prior HER2-targeted therapy or chemotherapy for metastatic disease.360 In the neoadjuvant setting, pertuzumab is approved in combination with trastu-zumab and docetaxel in HER2-positive, early stage breast cancers that are greater than 2 cm or node-positive. However, this approval is based on improvement in | Surgery_Schwartz. metastatic breast cancer patients who have previously received trastuzumab and a taxane either separately or in combination. T-DM1 is an antibody drug conjugate that incorporates the HER2 targeted activity of trastuzumab with the cytotoxic activity of DM1, a microtubule inhibitory agent leading to apoptosis.359Pertuzumab is a humanized monoclonal antibody that binds at a different epitope of the HER2 extracellular domain (subdomain II) and prevents dimerization of HER2 with other members of the family, primarily HER3. In the metastatic setting, it is approved in combination with trastuzumab and docetaxel for patients with metastatic HER2-positive breast cancer who have not received prior HER2-targeted therapy or chemotherapy for metastatic disease.360 In the neoadjuvant setting, pertuzumab is approved in combination with trastu-zumab and docetaxel in HER2-positive, early stage breast cancers that are greater than 2 cm or node-positive. However, this approval is based on improvement in |
Surgery_Schwartz_4067 | Surgery_Schwartz | is approved in combination with trastu-zumab and docetaxel in HER2-positive, early stage breast cancers that are greater than 2 cm or node-positive. However, this approval is based on improvement in pathologic complete response rate, and not data based on improvement in event free or overall survival.361,362 In the NeoSphere trial, neoadjuvant use of pertuzumab with trastuzumab and docetaxel led to nearly a 17% increase in pathologic complete response in the breast (P = .0141).361 While in the TRYPHAENA study, pathologic complete responses ranging from 57% to 66% were observed with neoadjuvant pertuzumab and trastuzumab combination given with anthracycline-containing or nonanthracycline-containing chemotherapy.362 With the use of dual antibody therapy, cur-rently there is significant interest in identifying patients who can avoid chemotherapy and potentially be treated with HER2-targeted agents alone. The NeoSphere study showed 27% pathologic complete response in HER2-positive, | Surgery_Schwartz. is approved in combination with trastu-zumab and docetaxel in HER2-positive, early stage breast cancers that are greater than 2 cm or node-positive. However, this approval is based on improvement in pathologic complete response rate, and not data based on improvement in event free or overall survival.361,362 In the NeoSphere trial, neoadjuvant use of pertuzumab with trastuzumab and docetaxel led to nearly a 17% increase in pathologic complete response in the breast (P = .0141).361 While in the TRYPHAENA study, pathologic complete responses ranging from 57% to 66% were observed with neoadjuvant pertuzumab and trastuzumab combination given with anthracycline-containing or nonanthracycline-containing chemotherapy.362 With the use of dual antibody therapy, cur-rently there is significant interest in identifying patients who can avoid chemotherapy and potentially be treated with HER2-targeted agents alone. The NeoSphere study showed 27% pathologic complete response in HER2-positive, |
Surgery_Schwartz_4068 | Surgery_Schwartz | interest in identifying patients who can avoid chemotherapy and potentially be treated with HER2-targeted agents alone. The NeoSphere study showed 27% pathologic complete response in HER2-positive, ER-negative, breast cancer patients treated with pertuzumab and trastuzumab alone. Pertuzumab was recently FDA approved in combination with trastuzumab and chemotherapy in the adjuvant setting in HER2 amplified breast cancers with high risk of recurrence. Approval is based on APHINITY trial showing that the addition of pertuzumab improved invasive disease free survival (7.1%) compared to placebo (8.7%) (HR 0.82, 95% CI: 0.67, 1.00; p = 0.047). Overall survival data is not mature.The ExteNET study evaluated the use of neratinib, an irreversible inhibitor of EGFR, HER2, and HER4, in HER2-positive early stage patients who have completed adjuvant trastuzumab. A year of neratinib after completion of chemo-therapy and trastuzumab-based adjuvant therapy significantly improved 2-year disease-free | Surgery_Schwartz. interest in identifying patients who can avoid chemotherapy and potentially be treated with HER2-targeted agents alone. The NeoSphere study showed 27% pathologic complete response in HER2-positive, ER-negative, breast cancer patients treated with pertuzumab and trastuzumab alone. Pertuzumab was recently FDA approved in combination with trastuzumab and chemotherapy in the adjuvant setting in HER2 amplified breast cancers with high risk of recurrence. Approval is based on APHINITY trial showing that the addition of pertuzumab improved invasive disease free survival (7.1%) compared to placebo (8.7%) (HR 0.82, 95% CI: 0.67, 1.00; p = 0.047). Overall survival data is not mature.The ExteNET study evaluated the use of neratinib, an irreversible inhibitor of EGFR, HER2, and HER4, in HER2-positive early stage patients who have completed adjuvant trastuzumab. A year of neratinib after completion of chemo-therapy and trastuzumab-based adjuvant therapy significantly improved 2-year disease-free |
Surgery_Schwartz_4069 | Surgery_Schwartz | early stage patients who have completed adjuvant trastuzumab. A year of neratinib after completion of chemo-therapy and trastuzumab-based adjuvant therapy significantly improved 2-year disease-free survival, the primary endpoint.363 After two years, invasive disease free survival was 94.2% in patients treated with neratinib compared with 91.9% in those receiving placebo (HR 0.66; 95% CI: 0.49, 0.90, p = 0.008) leading to FDA approval for HER2 amplified breast cancers following a year of adjuvant trastuzumab.In addition to amplifications or copy number alterations, activating mutations or single nucleotide variants in HER2 have been described (2%).364 Typically observed in ER-positive breast cancers, a higher prevalence of HER2 mutations have been reported in invasive lobular carcinomas, particularly in the pleomorphic subtype.365 These mutations, usually exclusive with HER2 amplification, are observed in kinase or extracellular domains and predict for responses or resistance to | Surgery_Schwartz. early stage patients who have completed adjuvant trastuzumab. A year of neratinib after completion of chemo-therapy and trastuzumab-based adjuvant therapy significantly improved 2-year disease-free survival, the primary endpoint.363 After two years, invasive disease free survival was 94.2% in patients treated with neratinib compared with 91.9% in those receiving placebo (HR 0.66; 95% CI: 0.49, 0.90, p = 0.008) leading to FDA approval for HER2 amplified breast cancers following a year of adjuvant trastuzumab.In addition to amplifications or copy number alterations, activating mutations or single nucleotide variants in HER2 have been described (2%).364 Typically observed in ER-positive breast cancers, a higher prevalence of HER2 mutations have been reported in invasive lobular carcinomas, particularly in the pleomorphic subtype.365 These mutations, usually exclusive with HER2 amplification, are observed in kinase or extracellular domains and predict for responses or resistance to |
Surgery_Schwartz_4070 | Surgery_Schwartz | particularly in the pleomorphic subtype.365 These mutations, usually exclusive with HER2 amplification, are observed in kinase or extracellular domains and predict for responses or resistance to HER2-targeting agents.366,367 A phase 2 trial of neratinib in HER2-mutated meta-static breast cancers showed a clinical benefit rate of 36% with one complete response and one partial response in a heavily pre-treated population. A clinical trial evaluating the combination of neratinib with fulvestrant, in HER2-mutated, ER-positive breast cancers, is in progress.SPECIAL CLINICAL SITUATIONSNipple DischargeUnilateral Nipple Discharge. Nipple discharge is a finding that can be seen in a number of clinical situations. It may be suggestive of cancer if it is spontaneous, unilateral, localized to a single duct, present in women ≥40 years of age, bloody, or associated with a mass. A trigger point on the breast may be present so that pressure around the nipple-areolar complex induces discharge from a | Surgery_Schwartz. particularly in the pleomorphic subtype.365 These mutations, usually exclusive with HER2 amplification, are observed in kinase or extracellular domains and predict for responses or resistance to HER2-targeting agents.366,367 A phase 2 trial of neratinib in HER2-mutated meta-static breast cancers showed a clinical benefit rate of 36% with one complete response and one partial response in a heavily pre-treated population. A clinical trial evaluating the combination of neratinib with fulvestrant, in HER2-mutated, ER-positive breast cancers, is in progress.SPECIAL CLINICAL SITUATIONSNipple DischargeUnilateral Nipple Discharge. Nipple discharge is a finding that can be seen in a number of clinical situations. It may be suggestive of cancer if it is spontaneous, unilateral, localized to a single duct, present in women ≥40 years of age, bloody, or associated with a mass. A trigger point on the breast may be present so that pressure around the nipple-areolar complex induces discharge from a |
Surgery_Schwartz_4071 | Surgery_Schwartz | duct, present in women ≥40 years of age, bloody, or associated with a mass. A trigger point on the breast may be present so that pressure around the nipple-areolar complex induces discharge from a single duct. In this circumstance, mammography and ultrasound are indicated for further evalu-ation. A ductogram also can be useful and is performed by can-nulating a single discharging duct with a small nylon catheter or needle and injecting 1.0 mL of water-soluble contrast solu-tion. Nipple discharge associated with a cancer may be clear, bloody, or serous. Testing for the presence of hemoglobin is helpful, but hemoglobin may also be detected when nipple dis-charge is secondary to an intraductal papilloma or duct ecta-sia. Definitive diagnosis depends on excisional biopsy of the offending duct and any associated mass lesion. A 3.0 lacrimal duct probe can be used to identify the duct that requires exci-sion. Another approach is to inject methylene blue dye within | Surgery_Schwartz. duct, present in women ≥40 years of age, bloody, or associated with a mass. A trigger point on the breast may be present so that pressure around the nipple-areolar complex induces discharge from a single duct. In this circumstance, mammography and ultrasound are indicated for further evalu-ation. A ductogram also can be useful and is performed by can-nulating a single discharging duct with a small nylon catheter or needle and injecting 1.0 mL of water-soluble contrast solu-tion. Nipple discharge associated with a cancer may be clear, bloody, or serous. Testing for the presence of hemoglobin is helpful, but hemoglobin may also be detected when nipple dis-charge is secondary to an intraductal papilloma or duct ecta-sia. Definitive diagnosis depends on excisional biopsy of the offending duct and any associated mass lesion. A 3.0 lacrimal duct probe can be used to identify the duct that requires exci-sion. Another approach is to inject methylene blue dye within |
Surgery_Schwartz_4072 | Surgery_Schwartz | of the offending duct and any associated mass lesion. A 3.0 lacrimal duct probe can be used to identify the duct that requires exci-sion. Another approach is to inject methylene blue dye within Brunicardi_Ch17_p0541-p0612.indd 59901/03/19 5:05 PM 600SPECIFIC CONSIDERATIONSPART IIthe duct after ductography. The nipple must be sealed with collodion or a similar material so that the blue dye does not discharge through the nipple but remains within the distended duct facilitating its localization. Localization with a wire or seed is performed when there is an associated mass that lies >2.0 to 3.0 cm from the nipple.Bilateral Nipple Discharge. Nipple discharge is suggestive of a benign condition if it is bilateral and multiductal in origin, occurs in women ≤39 years of age, or is milky or blue-green. Prolactin-secreting pituitary adenomas are responsible for bilat-eral nipple discharge in <2% of cases. If serum prolactin levels are repeatedly elevated, plain radiographs of the | Surgery_Schwartz. of the offending duct and any associated mass lesion. A 3.0 lacrimal duct probe can be used to identify the duct that requires exci-sion. Another approach is to inject methylene blue dye within Brunicardi_Ch17_p0541-p0612.indd 59901/03/19 5:05 PM 600SPECIFIC CONSIDERATIONSPART IIthe duct after ductography. The nipple must be sealed with collodion or a similar material so that the blue dye does not discharge through the nipple but remains within the distended duct facilitating its localization. Localization with a wire or seed is performed when there is an associated mass that lies >2.0 to 3.0 cm from the nipple.Bilateral Nipple Discharge. Nipple discharge is suggestive of a benign condition if it is bilateral and multiductal in origin, occurs in women ≤39 years of age, or is milky or blue-green. Prolactin-secreting pituitary adenomas are responsible for bilat-eral nipple discharge in <2% of cases. If serum prolactin levels are repeatedly elevated, plain radiographs of the |
Surgery_Schwartz_4073 | Surgery_Schwartz | or blue-green. Prolactin-secreting pituitary adenomas are responsible for bilat-eral nipple discharge in <2% of cases. If serum prolactin levels are repeatedly elevated, plain radiographs of the sellaturcica are indicated, and thin section CT scan is required. Optical nerve compression, visual field loss, and infertility are associated with large pituitary adenomas.Axillary Lymph Node Metastases in the Setting of an Unknown Primary CancerA woman who presents with an axillary lymph node metasta-sis that is consistent with a breast cancer metastasis has a 90% probability of harboring an occult breast cancer.303 However, axillary lymphadenopathy is the initial presenting sign in only 1% of breast cancer patients. Fine-needle aspiration biopsy or core-needle biopsy can be used to establish the diagnosis when an enlarged axillary lymph node is identified. When metastatic cancer is found, immunohistochemical analysis may classify the cancer as epithelial, melanocytic, or lymphoid in origin. | Surgery_Schwartz. or blue-green. Prolactin-secreting pituitary adenomas are responsible for bilat-eral nipple discharge in <2% of cases. If serum prolactin levels are repeatedly elevated, plain radiographs of the sellaturcica are indicated, and thin section CT scan is required. Optical nerve compression, visual field loss, and infertility are associated with large pituitary adenomas.Axillary Lymph Node Metastases in the Setting of an Unknown Primary CancerA woman who presents with an axillary lymph node metasta-sis that is consistent with a breast cancer metastasis has a 90% probability of harboring an occult breast cancer.303 However, axillary lymphadenopathy is the initial presenting sign in only 1% of breast cancer patients. Fine-needle aspiration biopsy or core-needle biopsy can be used to establish the diagnosis when an enlarged axillary lymph node is identified. When metastatic cancer is found, immunohistochemical analysis may classify the cancer as epithelial, melanocytic, or lymphoid in origin. |
Surgery_Schwartz_4074 | Surgery_Schwartz | diagnosis when an enlarged axillary lymph node is identified. When metastatic cancer is found, immunohistochemical analysis may classify the cancer as epithelial, melanocytic, or lymphoid in origin. The presence of hormone receptors (estrogen or progesterone receptors) suggests metastasis from a breast cancer but is not diagnostic. The search for a primary cancer includes careful examination of the thyroid, breast, and pelvis, including the rectum. The breast should be examined with diagnostic mam-mography, ultrasonography, and MRI to evaluate for an occult primary lesion. Further radiologic and laboratory studies should include chest radiography and liver function studies. Additional imaging of the chest, abdomen, and skeleton may be indicated if the extent of nodal involvement is consistent with stage III breast cancer. Suspicious findings on mammography, ultra-sonography, or MRI necessitate breast biopsy. When a breast cancer is found, treatment consists of an axillary lymph node | Surgery_Schwartz. diagnosis when an enlarged axillary lymph node is identified. When metastatic cancer is found, immunohistochemical analysis may classify the cancer as epithelial, melanocytic, or lymphoid in origin. The presence of hormone receptors (estrogen or progesterone receptors) suggests metastasis from a breast cancer but is not diagnostic. The search for a primary cancer includes careful examination of the thyroid, breast, and pelvis, including the rectum. The breast should be examined with diagnostic mam-mography, ultrasonography, and MRI to evaluate for an occult primary lesion. Further radiologic and laboratory studies should include chest radiography and liver function studies. Additional imaging of the chest, abdomen, and skeleton may be indicated if the extent of nodal involvement is consistent with stage III breast cancer. Suspicious findings on mammography, ultra-sonography, or MRI necessitate breast biopsy. When a breast cancer is found, treatment consists of an axillary lymph node |
Surgery_Schwartz_4075 | Surgery_Schwartz | with stage III breast cancer. Suspicious findings on mammography, ultra-sonography, or MRI necessitate breast biopsy. When a breast cancer is found, treatment consists of an axillary lymph node dissection with a mastectomy or preservation of the breast fol-lowed by whole-breast radiation therapy. Chemotherapy and endocrine therapy should be considered.Breast Cancer During PregnancyBreast cancer occurs in 1 of every 3000 pregnant women, and axillary lymph node metastases are present in up to 75% of these women.368 The average age of the pregnant woman with breast cancer is 34 years. Fewer than 25% of the breast nodules developing during pregnancy and lactation will be cancerous. Ultrasonography and needle biopsy specimens are used in the diagnosis of these nodules. Mammography is rarely indicated because of its decreased sensitivity during pregnancy and lac-tation; however, the fetus can be shielded if mammography is needed. Approximately 30% of the benign conditions encoun-tered will | Surgery_Schwartz. with stage III breast cancer. Suspicious findings on mammography, ultra-sonography, or MRI necessitate breast biopsy. When a breast cancer is found, treatment consists of an axillary lymph node dissection with a mastectomy or preservation of the breast fol-lowed by whole-breast radiation therapy. Chemotherapy and endocrine therapy should be considered.Breast Cancer During PregnancyBreast cancer occurs in 1 of every 3000 pregnant women, and axillary lymph node metastases are present in up to 75% of these women.368 The average age of the pregnant woman with breast cancer is 34 years. Fewer than 25% of the breast nodules developing during pregnancy and lactation will be cancerous. Ultrasonography and needle biopsy specimens are used in the diagnosis of these nodules. Mammography is rarely indicated because of its decreased sensitivity during pregnancy and lac-tation; however, the fetus can be shielded if mammography is needed. Approximately 30% of the benign conditions encoun-tered will |
Surgery_Schwartz_4076 | Surgery_Schwartz | because of its decreased sensitivity during pregnancy and lac-tation; however, the fetus can be shielded if mammography is needed. Approximately 30% of the benign conditions encoun-tered will be unique to pregnancy and lactation (galactoceles, lobular hyperplasia, lactating adenoma, and mastitis or abscess). Once a breast cancer is diagnosed, complete blood count, chest radiography (with shielding of the abdomen), and liver function studies are performed.Because of the potential deleterious effects of radiation therapy on the fetus, radiation cannot be considered until the fetus is delivered. A modified radical mastectomy can be per-formed during the first and second trimesters of pregnancy, even though there is an increased risk of spontaneous abortion after first-trimester anesthesia. During the third trimester, lumpec-tomy with axillary node dissection can be considered if adju-vant radiation therapy is deferred until after delivery. Lactation is suppressed. Chemotherapy | Surgery_Schwartz. because of its decreased sensitivity during pregnancy and lac-tation; however, the fetus can be shielded if mammography is needed. Approximately 30% of the benign conditions encoun-tered will be unique to pregnancy and lactation (galactoceles, lobular hyperplasia, lactating adenoma, and mastitis or abscess). Once a breast cancer is diagnosed, complete blood count, chest radiography (with shielding of the abdomen), and liver function studies are performed.Because of the potential deleterious effects of radiation therapy on the fetus, radiation cannot be considered until the fetus is delivered. A modified radical mastectomy can be per-formed during the first and second trimesters of pregnancy, even though there is an increased risk of spontaneous abortion after first-trimester anesthesia. During the third trimester, lumpec-tomy with axillary node dissection can be considered if adju-vant radiation therapy is deferred until after delivery. Lactation is suppressed. Chemotherapy |
Surgery_Schwartz_4077 | Surgery_Schwartz | During the third trimester, lumpec-tomy with axillary node dissection can be considered if adju-vant radiation therapy is deferred until after delivery. Lactation is suppressed. Chemotherapy administered during the first tri-mester carries a risk of spontaneous abortion and a 12% risk of birth defects. There is no evidence of teratogenicity resulting from administration of chemotherapeutic agents in the second and third trimesters. For this reason, many clinicians now con-sider the optimal strategy to be delivery of chemotherapy in the second and third trimesters as a neoadjuvant approach, which allows local therapy decisions to be made after the delivery of the baby. Pregnant women with breast cancer often present at a later stage of disease because breast tissue changes that occur in the hormone-rich environment of pregnancy obscure early cancers. However, pregnant women with breast cancer have a prognosis, stage by stage, that is similar to that of nonpregnant women with breast | Surgery_Schwartz. During the third trimester, lumpec-tomy with axillary node dissection can be considered if adju-vant radiation therapy is deferred until after delivery. Lactation is suppressed. Chemotherapy administered during the first tri-mester carries a risk of spontaneous abortion and a 12% risk of birth defects. There is no evidence of teratogenicity resulting from administration of chemotherapeutic agents in the second and third trimesters. For this reason, many clinicians now con-sider the optimal strategy to be delivery of chemotherapy in the second and third trimesters as a neoadjuvant approach, which allows local therapy decisions to be made after the delivery of the baby. Pregnant women with breast cancer often present at a later stage of disease because breast tissue changes that occur in the hormone-rich environment of pregnancy obscure early cancers. However, pregnant women with breast cancer have a prognosis, stage by stage, that is similar to that of nonpregnant women with breast |
Surgery_Schwartz_4078 | Surgery_Schwartz | the hormone-rich environment of pregnancy obscure early cancers. However, pregnant women with breast cancer have a prognosis, stage by stage, that is similar to that of nonpregnant women with breast cancer.Male Breast CancerFewer than 1% of all breast cancers occur in men.369,370 The inci-dence appears to be highest among North Americans and the British, in whom breast cancer constitutes as much as 1.5% of all male cancers. Jewish and African-American men have the highest incidence. Male breast cancer is preceded by gyneco-mastia in 20% of men. It is associated with radiation exposure, estrogen therapy, testicular feminizing syndromes, and Kline-felter’s syndrome (XXY). Breast cancer is rarely seen in young males and has a peak incidence in the sixth decade of life. A firm, nontender mass in the male breast requires investigation. Skin or chest wall fixation is particularly worrisome.DCIS makes up <15% of male breast cancer, whereas infil-trating ductal carcinoma makes up >85%. | Surgery_Schwartz. the hormone-rich environment of pregnancy obscure early cancers. However, pregnant women with breast cancer have a prognosis, stage by stage, that is similar to that of nonpregnant women with breast cancer.Male Breast CancerFewer than 1% of all breast cancers occur in men.369,370 The inci-dence appears to be highest among North Americans and the British, in whom breast cancer constitutes as much as 1.5% of all male cancers. Jewish and African-American men have the highest incidence. Male breast cancer is preceded by gyneco-mastia in 20% of men. It is associated with radiation exposure, estrogen therapy, testicular feminizing syndromes, and Kline-felter’s syndrome (XXY). Breast cancer is rarely seen in young males and has a peak incidence in the sixth decade of life. A firm, nontender mass in the male breast requires investigation. Skin or chest wall fixation is particularly worrisome.DCIS makes up <15% of male breast cancer, whereas infil-trating ductal carcinoma makes up >85%. |
Surgery_Schwartz_4079 | Surgery_Schwartz | mass in the male breast requires investigation. Skin or chest wall fixation is particularly worrisome.DCIS makes up <15% of male breast cancer, whereas infil-trating ductal carcinoma makes up >85%. Special-type cancers, including infiltrating lobular carcinoma, have occasionally been reported. Male breast cancer is staged in the same way as female breast cancer, and stage by stage, men with breast cancer have the same survival rate as women. Overall, men do worse because of the more advanced stage of their cancer (stage II, III or IV) at the time of diagnosis. The treatment of male breast cancer is surgi-cal, with the most common procedure being a modified radical mastectomy. SLN dissection has been shown to be feasible and accurate for nodal assessment in men presenting with a clinically node-negative axilla. Adjuvant radiation therapy is appropriate in cases in which there is a high risk for local-regional recurrence. Approximately 80% of male breast cancers are hormone | Surgery_Schwartz. mass in the male breast requires investigation. Skin or chest wall fixation is particularly worrisome.DCIS makes up <15% of male breast cancer, whereas infil-trating ductal carcinoma makes up >85%. Special-type cancers, including infiltrating lobular carcinoma, have occasionally been reported. Male breast cancer is staged in the same way as female breast cancer, and stage by stage, men with breast cancer have the same survival rate as women. Overall, men do worse because of the more advanced stage of their cancer (stage II, III or IV) at the time of diagnosis. The treatment of male breast cancer is surgi-cal, with the most common procedure being a modified radical mastectomy. SLN dissection has been shown to be feasible and accurate for nodal assessment in men presenting with a clinically node-negative axilla. Adjuvant radiation therapy is appropriate in cases in which there is a high risk for local-regional recurrence. Approximately 80% of male breast cancers are hormone |
Surgery_Schwartz_4080 | Surgery_Schwartz | a clinically node-negative axilla. Adjuvant radiation therapy is appropriate in cases in which there is a high risk for local-regional recurrence. Approximately 80% of male breast cancers are hormone recep-tor–positive, and adjuvant tamoxifen is considered. Systemic che-motherapy is considered for men with hormone receptor-negative cancers and for men with large primary tumors, multiple positive nodes, and locally advanced disease.Phyllodes TumorsThe nomenclature, presentation, and diagnosis of phyllodes tumors (including cystosarcoma phyllodes) have posed many problems for surgeons.371 These tumors are classified as benign, borderline, or malignant. Borderline tumors have a greater potential for local recurrence.Mammographic evidence of calcifications and morpho-logic evidence of necrosis do not distinguish between benign, borderline, and malignant phyllodes tumors. Consequently, it is difficult to differentiate benign phyllodes tumors from the Brunicardi_Ch17_p0541-p0612.indd | Surgery_Schwartz. a clinically node-negative axilla. Adjuvant radiation therapy is appropriate in cases in which there is a high risk for local-regional recurrence. Approximately 80% of male breast cancers are hormone recep-tor–positive, and adjuvant tamoxifen is considered. Systemic che-motherapy is considered for men with hormone receptor-negative cancers and for men with large primary tumors, multiple positive nodes, and locally advanced disease.Phyllodes TumorsThe nomenclature, presentation, and diagnosis of phyllodes tumors (including cystosarcoma phyllodes) have posed many problems for surgeons.371 These tumors are classified as benign, borderline, or malignant. Borderline tumors have a greater potential for local recurrence.Mammographic evidence of calcifications and morpho-logic evidence of necrosis do not distinguish between benign, borderline, and malignant phyllodes tumors. Consequently, it is difficult to differentiate benign phyllodes tumors from the Brunicardi_Ch17_p0541-p0612.indd |
Surgery_Schwartz_4081 | Surgery_Schwartz | do not distinguish between benign, borderline, and malignant phyllodes tumors. Consequently, it is difficult to differentiate benign phyllodes tumors from the Brunicardi_Ch17_p0541-p0612.indd 60001/03/19 5:05 PM 601THE BREASTCHAPTER 17malignant variant and from fibroadenomas. Phyllodes tumors are usually sharply demarcated from the surrounding breast tissue, which is compressed and distorted. Connective tissue composes the bulk of these tumors, which have mixed gelati-nous, solid, and cystic areas. Cystic areas represent sites of infarction and necrosis. These gross alterations give the gross cut tumor surface its classical leaf-like (phyllodes) appearance. The stroma of a phyllodes tumor generally has greater cellular activity than that of a fibroadenoma. After microdissection to harvest clusters of stromal cells from fibroadenomas and from phyllodes tumors, molecular biology techniques have shown the stromal cells of fibroadenomas to be either polyclonal or mono-clonal (derived | Surgery_Schwartz. do not distinguish between benign, borderline, and malignant phyllodes tumors. Consequently, it is difficult to differentiate benign phyllodes tumors from the Brunicardi_Ch17_p0541-p0612.indd 60001/03/19 5:05 PM 601THE BREASTCHAPTER 17malignant variant and from fibroadenomas. Phyllodes tumors are usually sharply demarcated from the surrounding breast tissue, which is compressed and distorted. Connective tissue composes the bulk of these tumors, which have mixed gelati-nous, solid, and cystic areas. Cystic areas represent sites of infarction and necrosis. These gross alterations give the gross cut tumor surface its classical leaf-like (phyllodes) appearance. The stroma of a phyllodes tumor generally has greater cellular activity than that of a fibroadenoma. After microdissection to harvest clusters of stromal cells from fibroadenomas and from phyllodes tumors, molecular biology techniques have shown the stromal cells of fibroadenomas to be either polyclonal or mono-clonal (derived |
Surgery_Schwartz_4082 | Surgery_Schwartz | clusters of stromal cells from fibroadenomas and from phyllodes tumors, molecular biology techniques have shown the stromal cells of fibroadenomas to be either polyclonal or mono-clonal (derived from a single progenitor cell), whereas those of phyllodes tumors are always monoclonal.Most malignant phyllodes tumors (Fig. 17-38) contain liposarcomatous or rhabdomyosarcomatous elements rather than fibrosarcomatous elements. Evaluation of the number of mitoses and the presence or absence of invasive foci at the tumor mar-gins may help to identify a malignant tumor. Small phyllodes tumors are excised with a margin of normal-appearing breast tissue. When the diagnosis of a phyllodes tumor with suspicious ABFigure 17-38. A. Malignant phyllodes tumor (cystosarcoma-phyllodes). B. Histologic features of a malignant phyllodes tumor (hematoxylin and eosin stain, ×100).malignant elements is made, reexcision of the biopsy specimen site to ensure complete excision of the tumor with a 1-cm mar-gin of | Surgery_Schwartz. clusters of stromal cells from fibroadenomas and from phyllodes tumors, molecular biology techniques have shown the stromal cells of fibroadenomas to be either polyclonal or mono-clonal (derived from a single progenitor cell), whereas those of phyllodes tumors are always monoclonal.Most malignant phyllodes tumors (Fig. 17-38) contain liposarcomatous or rhabdomyosarcomatous elements rather than fibrosarcomatous elements. Evaluation of the number of mitoses and the presence or absence of invasive foci at the tumor mar-gins may help to identify a malignant tumor. Small phyllodes tumors are excised with a margin of normal-appearing breast tissue. When the diagnosis of a phyllodes tumor with suspicious ABFigure 17-38. A. Malignant phyllodes tumor (cystosarcoma-phyllodes). B. Histologic features of a malignant phyllodes tumor (hematoxylin and eosin stain, ×100).malignant elements is made, reexcision of the biopsy specimen site to ensure complete excision of the tumor with a 1-cm mar-gin of |
Surgery_Schwartz_4083 | Surgery_Schwartz | of a malignant phyllodes tumor (hematoxylin and eosin stain, ×100).malignant elements is made, reexcision of the biopsy specimen site to ensure complete excision of the tumor with a 1-cm mar-gin of normal-appearing breast tissue is indicated. Large phyl-lodes tumors may require mastectomy. Axillary dissection is not recommended because axillary lymph node metastases rarely occur.Inflammatory Breast CarcinomaInflammatory breast carcinoma (stage IIIB) accounts for <3% of breast cancers. This cancer is characterized by the skin changes of brawny induration, erythema with a raised edge, and edema (peau d’orange).372 Permeation of the dermal lymph vessels by cancer cells is seen in skin biopsy specimens. There may be an associated breast mass (Fig. 17-39). The clinical differentia-tion of inflammatory breast cancer may be extremely difficult, especially when a locally advanced scirrhous carcinoma invades dermal lymph vessels in the skin to produce peau d’orange and lymphangitis (Table | Surgery_Schwartz. of a malignant phyllodes tumor (hematoxylin and eosin stain, ×100).malignant elements is made, reexcision of the biopsy specimen site to ensure complete excision of the tumor with a 1-cm mar-gin of normal-appearing breast tissue is indicated. Large phyl-lodes tumors may require mastectomy. Axillary dissection is not recommended because axillary lymph node metastases rarely occur.Inflammatory Breast CarcinomaInflammatory breast carcinoma (stage IIIB) accounts for <3% of breast cancers. This cancer is characterized by the skin changes of brawny induration, erythema with a raised edge, and edema (peau d’orange).372 Permeation of the dermal lymph vessels by cancer cells is seen in skin biopsy specimens. There may be an associated breast mass (Fig. 17-39). The clinical differentia-tion of inflammatory breast cancer may be extremely difficult, especially when a locally advanced scirrhous carcinoma invades dermal lymph vessels in the skin to produce peau d’orange and lymphangitis (Table |
Surgery_Schwartz_4084 | Surgery_Schwartz | inflammatory breast cancer may be extremely difficult, especially when a locally advanced scirrhous carcinoma invades dermal lymph vessels in the skin to produce peau d’orange and lymphangitis (Table 17-15). Inflammatory breast cancer also may be mistaken for a bacterial infection of the breast. More than 75% of women who have inflammatory breast cancer present with palpable axillary lymphadenopathy, and distant metastases also are frequently present. A PET-CT scan should be considered at the time of diagnosis to rule out concurrent metastatic disease. A report of the SEER program described distant metastases at diagnosis in 25% of white women with inflammatory breast carcinoma.Surgery alone and surgery with adjuvant radiation therapy have produced disappointing results in women with inflamma-tory breast cancer. However, neoadjuvant chemotherapy with an anthracycline-containing regimen may affect dramatic regres-sions in up to 75% of cases. Tumors should be assessed for HER2 and | Surgery_Schwartz. inflammatory breast cancer may be extremely difficult, especially when a locally advanced scirrhous carcinoma invades dermal lymph vessels in the skin to produce peau d’orange and lymphangitis (Table 17-15). Inflammatory breast cancer also may be mistaken for a bacterial infection of the breast. More than 75% of women who have inflammatory breast cancer present with palpable axillary lymphadenopathy, and distant metastases also are frequently present. A PET-CT scan should be considered at the time of diagnosis to rule out concurrent metastatic disease. A report of the SEER program described distant metastases at diagnosis in 25% of white women with inflammatory breast carcinoma.Surgery alone and surgery with adjuvant radiation therapy have produced disappointing results in women with inflamma-tory breast cancer. However, neoadjuvant chemotherapy with an anthracycline-containing regimen may affect dramatic regres-sions in up to 75% of cases. Tumors should be assessed for HER2 and |
Surgery_Schwartz_4085 | Surgery_Schwartz | inflamma-tory breast cancer. However, neoadjuvant chemotherapy with an anthracycline-containing regimen may affect dramatic regres-sions in up to 75% of cases. Tumors should be assessed for HER2 and hormone receptors with treatment dictated based on receptor status. Modified radical mastectomy is performed after demonstrated response to systemic therapy to remove residual cancer from the chest wall and axilla. Adjuvant chemotherapy may be indicated depending on final pathologic assessment of the breast and regional nodes. Finally, the chest wall and the Figure 17-39. Inflammatory breast carcinoma. Stage IIIB cancer of the breast with erythema, skin edema (peau d’orange), nipple retraction, and satellite skin nodules.Brunicardi_Ch17_p0541-p0612.indd 60101/03/19 5:06 PM 602SPECIFIC CONSIDERATIONSPART IIsupraclavicular, internal mammary, and axillary lymph node basins receive adjuvant radiation therapy. This multimodal approach results in 5-year survival rates that approach 30%. | Surgery_Schwartz. inflamma-tory breast cancer. However, neoadjuvant chemotherapy with an anthracycline-containing regimen may affect dramatic regres-sions in up to 75% of cases. Tumors should be assessed for HER2 and hormone receptors with treatment dictated based on receptor status. Modified radical mastectomy is performed after demonstrated response to systemic therapy to remove residual cancer from the chest wall and axilla. Adjuvant chemotherapy may be indicated depending on final pathologic assessment of the breast and regional nodes. Finally, the chest wall and the Figure 17-39. Inflammatory breast carcinoma. Stage IIIB cancer of the breast with erythema, skin edema (peau d’orange), nipple retraction, and satellite skin nodules.Brunicardi_Ch17_p0541-p0612.indd 60101/03/19 5:06 PM 602SPECIFIC CONSIDERATIONSPART IIsupraclavicular, internal mammary, and axillary lymph node basins receive adjuvant radiation therapy. This multimodal approach results in 5-year survival rates that approach 30%. |
Surgery_Schwartz_4086 | Surgery_Schwartz | CONSIDERATIONSPART IIsupraclavicular, internal mammary, and axillary lymph node basins receive adjuvant radiation therapy. This multimodal approach results in 5-year survival rates that approach 30%. Patients with inflammatory breast cancer should be encouraged to participate in clinical trials.Rare Breast CancersSquamous Cell (Epidermoid) Carcinoma. Squamous cell (epidermoid) carcinoma is a rare cancer that arises from metaplasia within the duct system and generally is devoid of distinctive clinical or radiographic characteristics.373 Regional metastases occur in 25% of patients, whereas distant metastases are rare.Adenoid Cystic Carcinoma. Adenoid cystic carcinoma is very rare, accounting for <0.1% of all breast cancers. It is typically indistinguishable from adenoid cystic carcinoma arising in sali-vary tissues. These cancers are generally 1 to 3 cm in diameter at presentation and are well circumscribed. Axillary lymph node metastases are rare, but deaths from pulmonary metastases | Surgery_Schwartz. CONSIDERATIONSPART IIsupraclavicular, internal mammary, and axillary lymph node basins receive adjuvant radiation therapy. This multimodal approach results in 5-year survival rates that approach 30%. Patients with inflammatory breast cancer should be encouraged to participate in clinical trials.Rare Breast CancersSquamous Cell (Epidermoid) Carcinoma. Squamous cell (epidermoid) carcinoma is a rare cancer that arises from metaplasia within the duct system and generally is devoid of distinctive clinical or radiographic characteristics.373 Regional metastases occur in 25% of patients, whereas distant metastases are rare.Adenoid Cystic Carcinoma. Adenoid cystic carcinoma is very rare, accounting for <0.1% of all breast cancers. It is typically indistinguishable from adenoid cystic carcinoma arising in sali-vary tissues. These cancers are generally 1 to 3 cm in diameter at presentation and are well circumscribed. Axillary lymph node metastases are rare, but deaths from pulmonary metastases |
Surgery_Schwartz_4087 | Surgery_Schwartz | in sali-vary tissues. These cancers are generally 1 to 3 cm in diameter at presentation and are well circumscribed. Axillary lymph node metastases are rare, but deaths from pulmonary metastases have been reported.Apocrine Carcinomas. Apocrine carcinomas are well-differentiated cancers that have rounded vesicular nuclei and prominent nucleoli. There is a very low mitotic rate and little variation in cellular features. However, apocrine carcinomas may display an aggressive growth pattern.Sarcomas. Sarcomas of the breast are histologically similar to soft tissue sarcomas at other anatomic sites. This diverse group includes fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, leiomyosarcoma, malignant schwannoma, rhab-domyosarcoma, osteogenic sarcoma, and chondrosarcoma. The clinical presentation is typically that of a large, painless breast mass with rapid growth. Diagnosis is by core-needle biopsy or by open incisional biopsy. Sarcomas are graded based on cellular-ity, degree of | Surgery_Schwartz. in sali-vary tissues. These cancers are generally 1 to 3 cm in diameter at presentation and are well circumscribed. Axillary lymph node metastases are rare, but deaths from pulmonary metastases have been reported.Apocrine Carcinomas. Apocrine carcinomas are well-differentiated cancers that have rounded vesicular nuclei and prominent nucleoli. There is a very low mitotic rate and little variation in cellular features. However, apocrine carcinomas may display an aggressive growth pattern.Sarcomas. Sarcomas of the breast are histologically similar to soft tissue sarcomas at other anatomic sites. This diverse group includes fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, leiomyosarcoma, malignant schwannoma, rhab-domyosarcoma, osteogenic sarcoma, and chondrosarcoma. The clinical presentation is typically that of a large, painless breast mass with rapid growth. Diagnosis is by core-needle biopsy or by open incisional biopsy. Sarcomas are graded based on cellular-ity, degree of |
Surgery_Schwartz_4088 | Surgery_Schwartz | is typically that of a large, painless breast mass with rapid growth. Diagnosis is by core-needle biopsy or by open incisional biopsy. Sarcomas are graded based on cellular-ity, degree of differentiation, nuclear atypia, and mitotic activity. Primary treatment is wide local excision, which may necessitate mastectomy. Axillary dissection is not indicated unless there is biopsy proven lymph node involvement. Angiosarcomas are classified as de novo, as postradiation, or as arising in associa-tion with postmastectomy lymphedema. In 1948, Stewart and Treves described lymphangiosarcoma of the upper extremity in women with ipsilateral lymphedema after radical mastectomy.374 Angiosarcoma is now the preferred name. The average interval between modified radical or radical mastectomy and the devel-opment of an angiosarcoma is 7 to 10 years. Sixty percent of women developing this cancer have a history of adjuvant radia-tion therapy. Forequarter amputation may be necessary to palli-ate the | Surgery_Schwartz. is typically that of a large, painless breast mass with rapid growth. Diagnosis is by core-needle biopsy or by open incisional biopsy. Sarcomas are graded based on cellular-ity, degree of differentiation, nuclear atypia, and mitotic activity. Primary treatment is wide local excision, which may necessitate mastectomy. Axillary dissection is not indicated unless there is biopsy proven lymph node involvement. Angiosarcomas are classified as de novo, as postradiation, or as arising in associa-tion with postmastectomy lymphedema. In 1948, Stewart and Treves described lymphangiosarcoma of the upper extremity in women with ipsilateral lymphedema after radical mastectomy.374 Angiosarcoma is now the preferred name. The average interval between modified radical or radical mastectomy and the devel-opment of an angiosarcoma is 7 to 10 years. Sixty percent of women developing this cancer have a history of adjuvant radia-tion therapy. Forequarter amputation may be necessary to palli-ate the |
Surgery_Schwartz_4089 | Surgery_Schwartz | devel-opment of an angiosarcoma is 7 to 10 years. Sixty percent of women developing this cancer have a history of adjuvant radia-tion therapy. Forequarter amputation may be necessary to palli-ate the ulcerative complications and advanced lymphedema.Lymphomas. Primary lymphomas of the breast are rare, and there are two distinct clinicopathologic variants. One type occurs in women ≤39 years of age, is frequently bilateral, and has the histologic features of Burkitt’s lymphoma. The second type is seen in women ≥40 years of age and is usually of the B-cell type. Breast involvement by Hodgkin’s lymphoma has been reported. An occult breast lymphoma may be diagnosed after detection of palpable axillary lymphadenopathy. Treatment depends on the stage of disease. Lumpectomy or mastectomy may be required. Axillary dissection for clearance of disease may be necessary. Recurrent or progressive local-regional disease is best man-aged by chemotherapy and radiation therapy. The prognosis is | Surgery_Schwartz. devel-opment of an angiosarcoma is 7 to 10 years. Sixty percent of women developing this cancer have a history of adjuvant radia-tion therapy. Forequarter amputation may be necessary to palli-ate the ulcerative complications and advanced lymphedema.Lymphomas. Primary lymphomas of the breast are rare, and there are two distinct clinicopathologic variants. One type occurs in women ≤39 years of age, is frequently bilateral, and has the histologic features of Burkitt’s lymphoma. The second type is seen in women ≥40 years of age and is usually of the B-cell type. Breast involvement by Hodgkin’s lymphoma has been reported. An occult breast lymphoma may be diagnosed after detection of palpable axillary lymphadenopathy. Treatment depends on the stage of disease. Lumpectomy or mastectomy may be required. Axillary dissection for clearance of disease may be necessary. Recurrent or progressive local-regional disease is best man-aged by chemotherapy and radiation therapy. The prognosis is |
Surgery_Schwartz_4090 | Surgery_Schwartz | be required. Axillary dissection for clearance of disease may be necessary. Recurrent or progressive local-regional disease is best man-aged by chemotherapy and radiation therapy. The prognosis is favorable, with 5and 10-year survival rates of 74% and 51%, respectively. More recently anaplastic large cell lymphoma has been described in association with breast implants for cosmetic or reconstructive purposes. This disease is treated with complete excision of the implant capsule with any associated soft tissue mass. More advanced cases may require systemic therapy and radiation treatment.REFERENCESEntries highlighted in bright blue are key references. 1. Breasted JH. The Edwin Smith Surgical Papyrus. University of Chicago Press, 1930;405. 2. Celsus AC. De Medicina (ed Loeb Classical Library Ed). Cambridge: Harvard University Press; 1935;131. 3. Beenken SW. History of the therapy of breast cancer. In: Copeland BA, ed. The Breast: Comprehensive Manage-ment of Benign and Malignant | Surgery_Schwartz. be required. Axillary dissection for clearance of disease may be necessary. Recurrent or progressive local-regional disease is best man-aged by chemotherapy and radiation therapy. The prognosis is favorable, with 5and 10-year survival rates of 74% and 51%, respectively. More recently anaplastic large cell lymphoma has been described in association with breast implants for cosmetic or reconstructive purposes. This disease is treated with complete excision of the implant capsule with any associated soft tissue mass. More advanced cases may require systemic therapy and radiation treatment.REFERENCESEntries highlighted in bright blue are key references. 1. Breasted JH. The Edwin Smith Surgical Papyrus. University of Chicago Press, 1930;405. 2. Celsus AC. De Medicina (ed Loeb Classical Library Ed). Cambridge: Harvard University Press; 1935;131. 3. Beenken SW. History of the therapy of breast cancer. In: Copeland BA, ed. The Breast: Comprehensive Manage-ment of Benign and Malignant |
Surgery_Schwartz_4091 | Surgery_Schwartz | Library Ed). Cambridge: Harvard University Press; 1935;131. 3. Beenken SW. History of the therapy of breast cancer. In: Copeland BA, ed. The Breast: Comprehensive Manage-ment of Benign and Malignant Disorder. Philadelphia: Saunders;2004;5. 4. Le Dran F. Mémoire avec une précis de plusieurs observa-tions sur le. Mem Acad Roy Chir Paris. 1757;3:1. 5. Moore C. On the influence of inadequate operations on the theory of cancer. R Med Chir Soc. 1867;1:244. 6. Halsted WS I. The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. Ann Surg. 1894;20:497-555. 7. Haagensen CD, Stout AP. Carcinoma of the breast. II-criteria of operability. Ann Surg. 1943;118:1032-1051. 8. Patey DH, Dyson WH. The prognosis of carcinoma of the breast in relation to the type of operation performed. Br J Cancer. 1948;2:7-13. 9. Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical | Surgery_Schwartz. Library Ed). Cambridge: Harvard University Press; 1935;131. 3. Beenken SW. History of the therapy of breast cancer. In: Copeland BA, ed. The Breast: Comprehensive Manage-ment of Benign and Malignant Disorder. Philadelphia: Saunders;2004;5. 4. Le Dran F. Mémoire avec une précis de plusieurs observa-tions sur le. Mem Acad Roy Chir Paris. 1757;3:1. 5. Moore C. On the influence of inadequate operations on the theory of cancer. R Med Chir Soc. 1867;1:244. 6. Halsted WS I. The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. Ann Surg. 1894;20:497-555. 7. Haagensen CD, Stout AP. Carcinoma of the breast. II-criteria of operability. Ann Surg. 1943;118:1032-1051. 8. Patey DH, Dyson WH. The prognosis of carcinoma of the breast in relation to the type of operation performed. Br J Cancer. 1948;2:7-13. 9. Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical |
Surgery_Schwartz_4092 | Surgery_Schwartz | of the breast in relation to the type of operation performed. Br J Cancer. 1948;2:7-13. 9. Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical mas-tectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347:567-575. 10. Keynes G. Conservative treatment of cancer of the breast. Br Med J. 1937;2(3):643-666. 11. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpec-tomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233-1241.Table 17-15Inflammatory vs. noninflammatory breast cancerINFLAMMATORYNONINFLAMMATORYDermal lymph vessel invasion is present with or without inflammatory changes.Inflammatory changes are present without dermal lymph vessel invasion.Cancer is not sharply delineated.Cancer is better delineated.Erythema and edema frequently involve >33% of the skin over the | Surgery_Schwartz. of the breast in relation to the type of operation performed. Br J Cancer. 1948;2:7-13. 9. Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical mas-tectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347:567-575. 10. Keynes G. Conservative treatment of cancer of the breast. Br Med J. 1937;2(3):643-666. 11. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpec-tomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233-1241.Table 17-15Inflammatory vs. noninflammatory breast cancerINFLAMMATORYNONINFLAMMATORYDermal lymph vessel invasion is present with or without inflammatory changes.Inflammatory changes are present without dermal lymph vessel invasion.Cancer is not sharply delineated.Cancer is better delineated.Erythema and edema frequently involve >33% of the skin over the |
Surgery_Schwartz_4093 | Surgery_Schwartz | changes are present without dermal lymph vessel invasion.Cancer is not sharply delineated.Cancer is better delineated.Erythema and edema frequently involve >33% of the skin over the breast.Erythema is usually confined to the lesion, and edema is less extensive.Lymph node involvement is present in >75% of cases.Lymph nodes are involved in approximately 50% of the cases.Distant metastases are more common at the initial presentation (25% of cases).Distant metastases are less common at presentation. Modified with permission from Bland KI, Copeland ED: The Breast: Comprehensive Management of Benign and Malignant Diseases, 2nd ed. Philadelphia, PA: Elsesvier/Saunders; 1998.Brunicardi_Ch17_p0541-p0612.indd 60201/03/19 5:06 PM 603THE BREASTCHAPTER 17 12. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. | Surgery_Schwartz. changes are present without dermal lymph vessel invasion.Cancer is not sharply delineated.Cancer is better delineated.Erythema and edema frequently involve >33% of the skin over the breast.Erythema is usually confined to the lesion, and edema is less extensive.Lymph node involvement is present in >75% of cases.Lymph nodes are involved in approximately 50% of the cases.Distant metastases are more common at the initial presentation (25% of cases).Distant metastases are less common at presentation. Modified with permission from Bland KI, Copeland ED: The Breast: Comprehensive Management of Benign and Malignant Diseases, 2nd ed. Philadelphia, PA: Elsesvier/Saunders; 1998.Brunicardi_Ch17_p0541-p0612.indd 60201/03/19 5:06 PM 603THE BREASTCHAPTER 17 12. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. |
Surgery_Schwartz_4094 | Surgery_Schwartz | R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366:2087-2106. 13. Peto R, Davies C, Godwin J, et al. Comparisons between dif-ferent polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. 14. Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adju-vant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378:771-784. 15. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869-10874. 16. Bland KI, Romrell LJ. Congenital and acquired disturbances of breast development and growth. In: Bland KI, Cope-land EMI, eds. The | Surgery_Schwartz. R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366:2087-2106. 13. Peto R, Davies C, Godwin J, et al. Comparisons between dif-ferent polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432-444. 14. Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adju-vant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378:771-784. 15. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869-10874. 16. Bland KI, Romrell LJ. Congenital and acquired disturbances of breast development and growth. In: Bland KI, Cope-land EMI, eds. The |
Surgery_Schwartz_4095 | Surgery_Schwartz | implications. Proc Natl Acad Sci U S A. 2001;98:10869-10874. 16. Bland KI, Romrell LJ. Congenital and acquired disturbances of breast development and growth. In: Bland KI, Cope-land EMI, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: WB Saunders; 1998:214. 17. Lonnerdal B. Nutritional and physiologic significance of human milk proteins. Am J Clin Nutr. 2003;77:1537S-1543S. 18. Rosenbloom AL. Breast physiology: normal and abnormal development and function. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: WB Saunders; 1998:38. 19. Van de Perre P. Transfer of antibody via mother’s milk. Vaccine. 2003;21(24):3374-3376. 20. Bland KI, Graves TA. Gynecomastia. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: WB Saunders; 1998:153. 21. Dixon JM. Outpatient treatment of non-lactational breast abscesses. Br J Surg. | Surgery_Schwartz. implications. Proc Natl Acad Sci U S A. 2001;98:10869-10874. 16. Bland KI, Romrell LJ. Congenital and acquired disturbances of breast development and growth. In: Bland KI, Cope-land EMI, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: WB Saunders; 1998:214. 17. Lonnerdal B. Nutritional and physiologic significance of human milk proteins. Am J Clin Nutr. 2003;77:1537S-1543S. 18. Rosenbloom AL. Breast physiology: normal and abnormal development and function. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: WB Saunders; 1998:38. 19. Van de Perre P. Transfer of antibody via mother’s milk. Vaccine. 2003;21(24):3374-3376. 20. Bland KI, Graves TA. Gynecomastia. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: WB Saunders; 1998:153. 21. Dixon JM. Outpatient treatment of non-lactational breast abscesses. Br J Surg. |
Surgery_Schwartz_4096 | Surgery_Schwartz | eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: WB Saunders; 1998:153. 21. Dixon JM. Outpatient treatment of non-lactational breast abscesses. Br J Surg. 1992;79:56-57. 22. Furlong AJ, al-Nakib L, Knox WF, et al. Periductal inflamma-tion and cigarette smoke. J Am Coll Surg. 1994;179:417-420. 23. Zuska JJ, Crile G, Jr., Ayres WW. Fistulas of lactifierous ducts. Am J Surg. 1951;81:312-317. 24. Dixon JM. Infection in surgical practice. In: Taylor EW, ed. Breast Surgery. Oxford: Oxford Medical Publications; 1992;187. 25. Dixon JM. Periductal mastitis and duct ectasia: an update. Breast. 1998;7:128-130. 26. Dixon JM, Kohlhardt SR, Dillon P. Total duct excision. Breast. 1998;7:216-219. 27. Frykberg ER, Bland KI. Current concepts on the biology and management of in situ (Tis, stage 0) breast carcinoma. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadel-phia: WB Saunders; | Surgery_Schwartz. eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadelphia: WB Saunders; 1998:153. 21. Dixon JM. Outpatient treatment of non-lactational breast abscesses. Br J Surg. 1992;79:56-57. 22. Furlong AJ, al-Nakib L, Knox WF, et al. Periductal inflamma-tion and cigarette smoke. J Am Coll Surg. 1994;179:417-420. 23. Zuska JJ, Crile G, Jr., Ayres WW. Fistulas of lactifierous ducts. Am J Surg. 1951;81:312-317. 24. Dixon JM. Infection in surgical practice. In: Taylor EW, ed. Breast Surgery. Oxford: Oxford Medical Publications; 1992;187. 25. Dixon JM. Periductal mastitis and duct ectasia: an update. Breast. 1998;7:128-130. 26. Dixon JM, Kohlhardt SR, Dillon P. Total duct excision. Breast. 1998;7:216-219. 27. Frykberg ER, Bland KI. Current concepts on the biology and management of in situ (Tis, stage 0) breast carcinoma. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadel-phia: WB Saunders; |
Surgery_Schwartz_4097 | Surgery_Schwartz | biology and management of in situ (Tis, stage 0) breast carcinoma. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadel-phia: WB Saunders; 1998:1020. 28. Camiel MR. Mondor’s disease in the breast. Am J Obstet Gynecol. 1985;152:879-881. 29. Mondor H. Tronculite sous-cutanée subaiguë de la paroi thoracique antero-latérale. Mem Acad Chir Paris. 1939; 65:1271. 30. Hughes LE, Mansel RE, Webster DJ. Aberrations of normal development and involution (ANDI): a new perspective on pathogenesis and nomenclature of benign breast disorders. Lancet. 1987;2:1316-1319. 31. Archer F, Omar M. The fine structure of fibro adenoma of the human breast. J Pathol. 1969;99:113-117. 32. Page DL, Anderson TJ. Diagnostic Histopathology of the Breast. Edinburgh: Churchill Livingstone; 1987. 33. Page DL, Simpson JF. Benign, high-risk, and premalignant lesions of the breast. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and | Surgery_Schwartz. biology and management of in situ (Tis, stage 0) breast carcinoma. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malignant Diseases. Philadel-phia: WB Saunders; 1998:1020. 28. Camiel MR. Mondor’s disease in the breast. Am J Obstet Gynecol. 1985;152:879-881. 29. Mondor H. Tronculite sous-cutanée subaiguë de la paroi thoracique antero-latérale. Mem Acad Chir Paris. 1939; 65:1271. 30. Hughes LE, Mansel RE, Webster DJ. Aberrations of normal development and involution (ANDI): a new perspective on pathogenesis and nomenclature of benign breast disorders. Lancet. 1987;2:1316-1319. 31. Archer F, Omar M. The fine structure of fibro adenoma of the human breast. J Pathol. 1969;99:113-117. 32. Page DL, Anderson TJ. Diagnostic Histopathology of the Breast. Edinburgh: Churchill Livingstone; 1987. 33. Page DL, Simpson JF. Benign, high-risk, and premalignant lesions of the breast. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and |
Surgery_Schwartz_4098 | Surgery_Schwartz | Churchill Livingstone; 1987. 33. Page DL, Simpson JF. Benign, high-risk, and premalignant lesions of the breast. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malig-nant Diseases. Philadelphia: WB Saunders; 1998:191. 34. Haagensen CD. Diseases of the Breast. 3rd ed. Philadelphia: WB Saunders; 1986. 35. Haagensen CD, Lane N, Lattes R, et al. Lobular neoplasia (so-called lobular carcinoma in situ) of the breast. Cancer. 1978;42:737-769. 36. Gadd MA, Souba WW. Evaluation and treatment of benign breast disorders. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malig-nant Diseases. Philadelphia: WB Saunders; 1998:233. 37. Marchant DJ. Benign breast disease. Obstet Gynecol Clin North Am. 2002;29:1-20. 38. Nurko J, Mabry CD, Whitworth P, et al. Interim results from the FibroAdenoma Cryoablation Treatment Registry. Am J Surg. 2005;190:647-651; discussion 651-652. 39. Dixon JM. Conservative management of fibroadenoma of | Surgery_Schwartz. Churchill Livingstone; 1987. 33. Page DL, Simpson JF. Benign, high-risk, and premalignant lesions of the breast. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malig-nant Diseases. Philadelphia: WB Saunders; 1998:191. 34. Haagensen CD. Diseases of the Breast. 3rd ed. Philadelphia: WB Saunders; 1986. 35. Haagensen CD, Lane N, Lattes R, et al. Lobular neoplasia (so-called lobular carcinoma in situ) of the breast. Cancer. 1978;42:737-769. 36. Gadd MA, Souba WW. Evaluation and treatment of benign breast disorders. In: Bland KI, Copeland EMI, eds. The Breast: Comprehensive Management of Benign and Malig-nant Diseases. Philadelphia: WB Saunders; 1998:233. 37. Marchant DJ. Benign breast disease. Obstet Gynecol Clin North Am. 2002;29:1-20. 38. Nurko J, Mabry CD, Whitworth P, et al. Interim results from the FibroAdenoma Cryoablation Treatment Registry. Am J Surg. 2005;190:647-651; discussion 651-652. 39. Dixon JM. Conservative management of fibroadenoma of |
Surgery_Schwartz_4099 | Surgery_Schwartz | Whitworth P, et al. Interim results from the FibroAdenoma Cryoablation Treatment Registry. Am J Surg. 2005;190:647-651; discussion 651-652. 39. Dixon JM. Conservative management of fibroadenoma of the breast. Br J Surg. 1996;83:1798-1799. 40. Atkins HJ. Mammillary fistula. Br Med J. 1955;2:1473-1474. 41. Dixon JM, Thompson AM. Effective surgical treatment for mammary duct fistula. Br J Surg. 1991;78:1185-1186. 42. Bernstein L, Henderson BE, Hanisch R, et al. Physical exer-cise and reduced risk of breast cancer in young women. J Natl Cancer Inst. 1994;86:1403-1408. 43. Blackburn GL, Copeland T, Khaodhiar L, et al. Diet and breast cancer. J Womens Health (Larchmt). 2003;12: 183-192. 44. Goss PE, Sierra S. Current perspectives on radiation-induced breast cancer. J Clin Oncol. 1998;16:338-347. 45. Hulka BS. Epidemiologic analysis of breast and gynecologic cancers. Prog Clin Biol Res. 1997;396:17-29. 46. Pujol P, Galtier-Dereure F, Bringer J: Obesity and breast cancer risk. Hum Reprod. | Surgery_Schwartz. Whitworth P, et al. Interim results from the FibroAdenoma Cryoablation Treatment Registry. Am J Surg. 2005;190:647-651; discussion 651-652. 39. Dixon JM. Conservative management of fibroadenoma of the breast. Br J Surg. 1996;83:1798-1799. 40. Atkins HJ. Mammillary fistula. Br Med J. 1955;2:1473-1474. 41. Dixon JM, Thompson AM. Effective surgical treatment for mammary duct fistula. Br J Surg. 1991;78:1185-1186. 42. Bernstein L, Henderson BE, Hanisch R, et al. Physical exer-cise and reduced risk of breast cancer in young women. J Natl Cancer Inst. 1994;86:1403-1408. 43. Blackburn GL, Copeland T, Khaodhiar L, et al. Diet and breast cancer. J Womens Health (Larchmt). 2003;12: 183-192. 44. Goss PE, Sierra S. Current perspectives on radiation-induced breast cancer. J Clin Oncol. 1998;16:338-347. 45. Hulka BS. Epidemiologic analysis of breast and gynecologic cancers. Prog Clin Biol Res. 1997;396:17-29. 46. Pujol P, Galtier-Dereure F, Bringer J: Obesity and breast cancer risk. Hum Reprod. |
Surgery_Schwartz_4100 | Surgery_Schwartz | BS. Epidemiologic analysis of breast and gynecologic cancers. Prog Clin Biol Res. 1997;396:17-29. 46. Pujol P, Galtier-Dereure F, Bringer J: Obesity and breast cancer risk. Hum Reprod. 1997;12(1):116-125. 47. Singletary SE. Rating the risk factors for breast cancer. Ann Surg. 2003;237:474-482. 48. Wynder EL, Cohen LA, Muscat JE, et al. Breast cancer: weighing the evidence for a promoting role of dietary fat. J Natl Cancer Inst. 1997;89:766-775. 49. Baan R, Straif K, Grosse Y, et al. Carcinogenicity of alcoholic beverages. Lancet Oncol. 2007;8:292-293. 50. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute, based on November 2012 SEER data submission. Bethesda; 2013. 51. Domchek SM, Eisen A, Calzone K, et al. Application of breast cancer risk prediction models in clinical practice. J Clin Oncol. 2003;21:593-601. 52. Gail MH, Brinton LA, Byar DP, et al. Projecting individu-alized probabilities of developing breast cancer for | Surgery_Schwartz. BS. Epidemiologic analysis of breast and gynecologic cancers. Prog Clin Biol Res. 1997;396:17-29. 46. Pujol P, Galtier-Dereure F, Bringer J: Obesity and breast cancer risk. Hum Reprod. 1997;12(1):116-125. 47. Singletary SE. Rating the risk factors for breast cancer. Ann Surg. 2003;237:474-482. 48. Wynder EL, Cohen LA, Muscat JE, et al. Breast cancer: weighing the evidence for a promoting role of dietary fat. J Natl Cancer Inst. 1997;89:766-775. 49. Baan R, Straif K, Grosse Y, et al. Carcinogenicity of alcoholic beverages. Lancet Oncol. 2007;8:292-293. 50. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute, based on November 2012 SEER data submission. Bethesda; 2013. 51. Domchek SM, Eisen A, Calzone K, et al. Application of breast cancer risk prediction models in clinical practice. J Clin Oncol. 2003;21:593-601. 52. Gail MH, Brinton LA, Byar DP, et al. Projecting individu-alized probabilities of developing breast cancer for |
Surgery_Schwartz_4101 | Surgery_Schwartz | cancer risk prediction models in clinical practice. J Clin Oncol. 2003;21:593-601. 52. Gail MH, Brinton LA, Byar DP, et al. Projecting individu-alized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989;81:1879-1886. 53. Edwards BK, Brown ML, Wingo PA, et al. Annual report to the nation on the status of cancer, 1975-2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst. 2005;97:1407-1427. 54. Chen J, Pee D, Ayyagari R, et al. Projecting absolute invasive breast cancer risk in white women with a model that includes mammographic density. J Natl Cancer Inst. 2006;98:1215-1226. 55. Claus EB, Risch N, Thompson WD. The calculation of breast cancer risk for women with a first degree family history of ovarian cancer. Breast Cancer Res Treat. 1993;28:115-120. 56. Kerlikowske K, Ichikawa L, Miglioretti DL, et al. Longitudi-nal measurement of clinical mammographic breast density to improve estimation of | Surgery_Schwartz. cancer risk prediction models in clinical practice. J Clin Oncol. 2003;21:593-601. 52. Gail MH, Brinton LA, Byar DP, et al. Projecting individu-alized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989;81:1879-1886. 53. Edwards BK, Brown ML, Wingo PA, et al. Annual report to the nation on the status of cancer, 1975-2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst. 2005;97:1407-1427. 54. Chen J, Pee D, Ayyagari R, et al. Projecting absolute invasive breast cancer risk in white women with a model that includes mammographic density. J Natl Cancer Inst. 2006;98:1215-1226. 55. Claus EB, Risch N, Thompson WD. The calculation of breast cancer risk for women with a first degree family history of ovarian cancer. Breast Cancer Res Treat. 1993;28:115-120. 56. Kerlikowske K, Ichikawa L, Miglioretti DL, et al. Longitudi-nal measurement of clinical mammographic breast density to improve estimation of |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.