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Triphenylphosphonium conjugated gold nanotriangles impact Pi3KAKT pathway in breast cancer cells a photodynamic therapy approach.

Although gold nanoparticles based photodynamic therapy (PDT) were reported to improve efficacy and specificity, the impact of surface charge in targeting cancer is still a challenge. Herein, we report gold nanotriangles (AuNTs) tuned with anionic and cationic surface charge conjugating triphenylphosphonium (TPP) targeting breast cancer cells with 5-aminoleuvinic acid (5-ALA) based PDT, in vitro. Optimized surface charge of AuNTs with and without TPP kill breast cancer cells. By combining, 5-ALA and PDT, the surface charge augmented AuNTs deliver improved cellular toxicity as revealed by MTT, fluorescent probes and flow cytometry. Further, the 5-ALA and PDT treatment in the presence of AuNTs impairs cell survival Pi3KAKT signaling pathway causing mitochondrial dependent apoptosis. The cumulative findings demonstrate that, cationic AuNTs with TPP excel selective targeting of breast cancer cells in the presence of 5-ALA and PDT.

The Absence of Cancer in the Location of a Breast Tissue Marker After Neoadjuvant Chemotherapy may Predict Pathological Complete Response with High Accuracy Results from a Phase II Trial.

It is difficult to determine pathological complete response (pCR) before surgery in clinical complete response (cCR) cases by imaging alone. We designed a prospective study to evaluate whether a breast tissue marker placed in a tumor before neoadjuvant chemotherapy (NAC) can predict a pCR, possibly removing the need for surgery. We recruited patients with primary invasive breast cancer assigned to undergo curative surgery and possible NAC. A breast marker (UltraClip A total of 102 patients were enrolled. Patients were categorized by cancer stage and subtypes. Seventy-two patients (70.6%) received standard NAC 23 (34.3%) attained cCR, of whom pCR was obtained in 12 (52.2%). The probability of no cancer in the markers location but cancer in the removed specimens was 4.3% (95% confidence interval, 0.1-21.9). The false-negative rate was 9.1% (111), and the negative predictive value was 92.3% (1213). In only one case, no cancer was found in the markers location, but cancer cells were present in the removed specimen. The absence of cancer in the location of a breast tissue marker after NAC predicted pCR with high accuracy. Therefore, the rebiopsy of a markers location might mean surgery is unnecessary.

Contrast-enhanced mammography in the assessment of residual disease after neoadjuvant treatment.

To investigate the utility of contrast-enhanced mammography (CEM) as an alternative to breast MRI for the evaluation of residual disease after neoadjuvant treatment (NAT). This prospective study enrolled consecutive women undergoing NAT for breast cancer from July 2017-July 2019. Breast MRI and CEM exams performed after completion of NAT were read independently by two breast radiologists. Residual disease and lesion size on MRI and CEM recombined (RI) and low-energy images (LEI) were compared. Histopathology was considered the reference standard. Statistical analysis was performed using McNemars and Leisenrings tests. Multiple comparison adjustment was made using Bonferroni procedure. Lesion sizes were correlated using Kendalls tau coefficient. There were 110 participants with 115 breast cancers. Residual disease (invasive cancer or ductal carcinoma in situ) was detected in 83115 (72%) lesions on pathology, 71115 (62%) on MRI, 55115 (48%) on CEM RI, and 75115 (65%) on CEM LEI. When using multiple comparison adjustment, no significant differences were detected between MRI combined with CEM LEI and CEM RI combined with CEM LEI, in terms of accuracy (MRI 77%, CEM 72% p ≥ 0.99), sensitivity (MRI 88%, CEM 81% p ≥ 0.99), specificity (MRI 47%, CEM 50% p ≥ 0.99), PPV (MRI 81%, CEM 81% p ≥ 0.99), or NPV (MRI 60%, CEM 50% p ≥ 0.99). Size correlation between pathology and both MRI combined with CEM LEI and CEM RI combined with CEM LEI was moderate τ 0. 36 vs 0.33 (p ≥ 0.99). Contrast-enhanced mammography is an acceptable alternative to breast MRI for the detection of residual disease after neoadjuvant treatment.

YBX1lncRNA SBF2-AS1 interaction regulates proliferation and tamoxifen sensitivity via PI3KAKTMTOR signaling in breast cancer cells.

Y-box binding protein 1 (YBX1) is a multifunctional oncoprotein that can interact with several long non-coding RNAs (lncRNAs) to regulate metastasis in malignancies including breast cancer (BC). In the present study, we demonstrated the association of YBX1 with oncogenic lncRNA SBF2-AS1 (SET-binding factor 2 antisense RNA 1) via PI3KAKTmTOR signaling to regulate BC cell proliferation. We further explored the involvement of the YBX1SBF2-AS1PI3KAKTmTOR axis in the restoration of tamoxifen (TAM) sensitivity. YBX1-SBF2-AS1 association was predicted in silico and verified by RNA immunoprecipitation (RIP)-qPCR assay. Transfection experiments, Real-time RT PCR, Western blots, Phospho AKTmTOR antibody array kit, and cell proliferationapoptosis assays were employed to detect the YBX1SBF2-AS1 PI3KAKTmTOR axis and its effects upon TAM treatment in vitro. We identified that the YBX1 protein specifically binds to lncRNA SBF2-AS1. Our transfection experiments in MCF-7 and MDA-MB-468 cells with SBF2-AS1 silenced or overexpressed YBX1 plasmids, and their negative controls revealed that YBX1 regulates the expression of SBF2-AS1 by forming a positive feedback loop for its activation. We further demonstrated YBX1-SBF2-AS1 association exerts its effects on cell proliferation via PI3KAKTmTOR signaling pathway. Furthermore, we observed an increase in TAM sensitivity in BC cells after the knockdown of YBX1-SBF2-AS1 marked by decreased cell proliferation through disruption of the PI3KAKTmTOR axis. Our study has identified a novel YBX1SBF2-AS1PI3KAKTmTOR regulatory axis which may serve as a potential target to improve the effectiveness and efficacy of TAM treatment in BC.

Schwann cell-derived CXCL2 contributes to cancer pain by modulating macrophage infiltration in a mouse breast cancer model.

Pain is one of the most severe complications affecting the quality of life of cancer patients. Although substantial progress has been made in the diagnosis and treatment of cancer, the neurobiological mechanism of cancer pain is still unclear. In the present study, we identified the critical role of CXC chemokine 2 (CXCL2), released by Schwann cells after being activated by cancer cells, in maintaining cancer-induced macrophage infiltration and the resulting mechanical hypersensitivity and persistent spontaneous nociception. In vitro, Schwann cells cocultured with breast cancer cells exhibited a significant increase in CXCL2 expression in addition, conditioned medium from Schwann cells activated by breast cancer cells had a similar effect to recombinant CXCL2 in terms of inducing macrophage migration. Targeting CXCL2 signaling by both CXC chemokine receptor 2 (CXCR2) antagonist pharmacological blockade and anti-CXCL2 mAb immunological blockade robustly prevented conditioned medium-induced macrophage migration. In vivo, both application of recombinant CXCL2 and perineural breast cancer cell implantation resulted in mechanical hypersensitivity and persistent spontaneous nociception in mice, along with increased macrophage infiltration into the sciatic nerves. Similar to the in vitro results, inhibition of CXCL2CXCR2 signaling or conditional knockdown of CXCL2 in sciatic nerve Schwann cells effectively attenuated breast cancer cell-induced mechanical hypersensitivity, persistent spontaneous nociception, and macrophage recruitment in the sciatic nerve. Mechanistically, we found that redox effector factor-1 (Ref-1) secreted by breast cancer cells activated hypoxia inducible factor-1α (HIF-1α) expression and inhibited reactive oxygen species (ROS) production in Schwann cells, ultimately inducing CXCL2 expression in Schwann cells. In brief, the present study expands new insights into cancer pain mechanisms from promising animal models to provide new strategies for the control of cancer pain.

Isopimaric acid, an ion channel regulator, regulates calcium and oxidative phosphorylation pathways to inhibit breast cancer proliferation and metastasis.

Breast cancer is the globally most common malignant tumor and the biggest threat to women. Even though the diagnosis and treatment of breast cancer are progressing continually, a large number of breast cancer patients eventually develop a metastatic tumor, especially triple-negative breast cancer (TNBC). Recently, metal ion homeostasis and ion signaling pathway have become important targets for cancer therapy. In this study, We analyzed the effects and mechanisms of isopimaric acid (IPA), an ion channel regulator, on the proliferation and metastasis of breast cancer cells (4 T1, MDA-MB-231and MCF-7) by cell functional assay, flow cytometry, western blot, proteomics and other techniques in vitro and in vivo. Results found that IPA significantly inhibited the proliferation and metastasis of breast cancer cells (especially 4 T1). Further studies on the anti-tumor mechanism of IPA suggested that IPA might affect EMT and Wnt signaling pathways by targeting mitochondria oxidative phosphorylation and Ca

CRISPRCas genome editing in triple negative breast cancer Current situation and future directions.

Triple negative breast cancer (TNBC) has been well-known to be closely associated with the abnormal expression of both oncogenes and tumor suppressors. Although several pathogenic mutations in TNBC have been identified, the current therapeutic strategy is usually aimed at symptom relief rather than correcting mutations in the DNA sequence. Of note, clustered regularly interspaced short palindromic repeats (CRISPR)CRISPR-associated protein (Cas) has been gradually regarded as a breakthrough gene-editing tool with potential therapeutic applications in human cancers, including TNBC. Thus, in this review, we focus on summarizing the molecular subtypes of TNBC, as well as the CRISPR system and its potential applications in TNBC treatment. Moreover, we further discuss several emerging strategies for utilizing the CRISPRCas system to aid in the precise diagnosis of TNBC, as well as the limitations of the CRISPRCas system. Taken together, these findings would demonstrate that CRISPRCas system is not only an effective genome editing tool in TNBC, but a promising strategy for the future therapeutic purposes.

Hsacirc0001925 promotes malignant progression in triple-negative breast cancer via miR-1299YY1 axis.

Circular RNAs (circRNAs) are related to the pathogenesis and progression of triple-negative breast cancer (TNBC). The aim of this study was to investigate the role and mechanism of hsacirc0001925 in TNBC progression. Hsacirc0001925, microRNA (miR)-1299 and Yin Yang 1 (YY1) levels were examined in TNBC via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2-deoxyuridine (EdU) staining, flow cytometry, wound healing assay and tube formation assay were conducted to estimate the effects of hsacirc0001925 on malignant phenotypes of TNBC tumors. Several protein levels were measured with western blot. The regulatory relationship between miR-1299 and hsacirc0001925 or YY1 was validated using a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft assay was used to estimate the effect of hsacirc0001925 in TNBC in vivo. Hsacirc0001925 and YY1 levels were upregulated, while miR-1299 abundance was downregulated in TNBC tissues and cells. Hsacirc0001925 silencing constrained cell proliferation, migration and angiogenesis whereas it promoted apoptosis in vitro, and hsacirc0001925 silencing significantly curbed xenograft tumor growth in vivo. Hsacirc0001925 acted as a miRNA sponge for miR-1299. Hsacirc0001925 decreased YY1 expression by sponging miR-1299. MiR-1299 downregulation alleviated the effects of hsacirc0001925 knockdown on BC progression. MiR-1299 interacted with the 3 untranslated region (3 UTR) of YY1, and YY1 overexpression partly reversed the effects of miR-1299 overexpression on BC progression. Our findings showed that hsacirc0001925 mediated TNBC progression via regulating miR-1299YY1 axis, providing a potential target for BC treatment.

Impact of Geriatric Assessment on the Tolerability of Combination Chemotherapy in Older Patients with Advanced Cancer A Matched-Pair Analysis.

Because of their individual vulnerabilities, treatment decisions for older patients can be difficult. Geriatric assessment (GA) may help to select patients for systemic treatment, but its value is still unproven. Older cancer patients (≥65 years of age) with and without complex GA followed by discussion in the geriatric-oncologic conference, who had been treated in palliative intention with standard combination chemotherapy at the Evang. Kliniken Essen-Mitte, were retrospectively evaluated. All patients had been orally informed about the treatment options and had chosen chemotherapy beside supportive care. To reduce selection bias, the method of propensity-score matching was performed. Patient groups treated in the years 2011-2013 (without GA, group 1) and in the years 2014-2015 (with GA, group 2) were compared regarding different toxicity endpoints. The primary endpoint of the study was defined as numbers of patients with unplanned admission to the hospital or death during first-line chemotherapy and GA should reduce these events by 15%. Overall, 114 patients were evaluated in both groups. The median age was 74 years. Patients suffered from gastrointestinal carcinomas (47%), lung cancer (28%), breast cancer (12%), and other cancer types (3%). Consequently, most patients were treated with platinum-based (41%), fluoropyrimidine-based (35%), or anthracycline-based (13%) combination chemotherapy. In group 2, the events were numerically lower for all toxicity endpoints. The need for a premature stop of treatment was 54.4% in group 1 compared to 29.8% in group 2 (p < 0.01) and also the treatment-related mortality was significantly lower in group 2 (17.5% vs. 5.3% p 0.04). The primary endpoint, the rate of unplanned hospital admission, and death was 49.1% versus 35.1% (difference 14.0%), which did not reach the predefined border of 15%. There was a nonsignificant overall survival benefit in the group with GA (22.6 vs. 18.4 months). GA appears useful to better select older patients with advanced cancer for combination chemotherapy. The significant reduction of mortality during chemotherapy justifies the efforts and costs which need to be expended. To evaluate the effect of GA on overall survival, prospective trials are required.

Cancer burden in adolescents and young adults in Europe.

Cancer epidemiology is unique in adolescents and young adults (AYAs aged 15-39 years). The European Society for Medical OncologyEuropean Society for Paediatric Oncology (ESMOSIOPE) AYA Working Group aims to describe the burden of cancers in AYAs in Europe and across European Union (EU) countries. We used data available on the Global Cancer Observatory. We retrieved crude and age-standardised (World Standard Population) incidence and mortality rates. We reported about AYA cancer burden in Europe and between 28 EU member states. We described incidence and mortality for all cancers and for the 13 cancers most relevant to the AYA population. Incidence and mortality varied widely between countries with the highest mortality observed in Eastern EU countries. Cancers of the female breast, thyroid and male testis were the most common cancers across countries followed by melanoma of skin and cancers of the cervix. Variations in cancer incidence rates across different populations may reflect different distribution of risk factors, variations in the implementation or uptake of screening as well as overdiagnosis. AYA cancer mortality disparities may be due to variation in early-stage diagnoses, different public education and awareness of cancer symptoms, different degrees of access or availability of treatment. Our results highlight the future health care needs and requirements for AYA-specialised services to ensure a homogeneous treatment across different countries as well as the urgency for preventive initiatives that can mitigate the increasing burden.

The impact of endoxifen-guided tamoxifen dose reductions on endocrine side-effects in patients with primary breast cancer.

Tamoxifen is important in the adjuvant treatment of hormone-sensitive breast cancer and substantially reduces recurrence however, almost 50% of patients are non-compliant mainly due to side-effects. The aim of this study was to investigate whether endoxifen-guided tamoxifen dose reduction could lead to fewer side-effects. Effects of tamoxifen dose reduction were investigated in patients with bothersome side-effects and endoxifen levels ≥32 nM and compared to patients with side-effects who remained on tamoxifen 20 mg. Endocrine symptoms and health-related quality of life (HR-QOL) were assessed after 3 months with the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) questionnaire. Tamoxifen dose was reduced in 20 patients, 17 of whom were assessable for side-effect analyses. A clinically relevant improvement of >6 points was observed in endocrine symptoms and HR-QOL in 41% and 65% of the patients, respectively. In total, there was a significant and clinically relevant improvement in endocrine symptoms 5.7, 95% confidence interval (CI) -0.5-11.5 and HR-QOL (8.2, 95% CI 0.9-15.4) after dose reduction. This was not seen in patients whose doses were not reduced (n 60). In 21% of patients, endoxifen dropped slightly below the 16-nM threshold (12.8, 15.5, 15.8, 15.9 nM). Endoxifen-guided dose reduction of tamoxifen significantly improved tamoxifen-related side-effects and HR-QOL. Nearly 80% of patients remained above the most conservative endoxifen threshold.

Synthesis, evaluation of anti-breast cancer activity in vitro of ICS II derivatives and summary of the structure-activity relationship.

A series of Icariside II (ICS II) derivatives were synthesized, and their structure-activity relationships (SARs) were studied in this paper. The in vitro antitumor activities towards human breast cancer cell lines (MCF-7) were evaluated by Cell Counting Kit-8 (CCK-8 kit). Preliminary results showed that, compared with ICS II, most of the derivatives displayed good micromole level activities. Among the series of derivatives, the S27, which totally acetylated hydroxyl of ICS II, possessed highest cytotoxicity, with IC

The interplay of arsenic, silymarin, and NF-ĸB pathway in male reproductive toxicity A review.

Arsenic toxicity is one of the most trending reasons for several malfunctions, particularly reproductive toxicity. The exact mechanism of arsenic poisoning is a big question mark. Exposure to arsenic reduces sperm count, impairs fertilization, and causes inflammation and genotoxicity through interfering with autophagy, epigenetics, ROS generation, downregulation of essential protein expression, metabolite changes, and hampering several signaling cascades, particularly by the alteration of NF-ĸB pathway. This work tries to give a clear idea about the different aspects of arsenic resulting in male reproductive complications, often leading to infertility. The first part of this article explains the implications of arsenic poisoning and the crosstalk of the NF-ĸB pathway in male reproductive toxicity. Silymarin is a bioactive compound that exerts anti-cancer and anti-inflammatory properties and has demonstrated hopeful outcomes in several cancers, including colon cancer, breast cancer, and skin cancer, by downregulating the hyperactive NF-ĸB pathway. The next half of this article thus sheds light on silymarins therapeutic potential in inhibiting the NF-ĸB signaling cascade, thus offering protection against arsenic-induced male reproductive toxicity.

Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway.

The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. BCSCs from breast cancer cell lines (MDA-MB-231 and MCF-7) were enriched using a tumorsphere formation assay. Gene and protein expression was detected by measurement of quantitative real-time reverse transcription PCR, western blot, and immunofluorescence assays. Transient transfection assays were used to evaluate the involvement of Gli1, a signaling pathway molecule and ΔNp63α, an oncogene in influencing the PAE-induced characteristics of BCSCs. PAE (butylbenzyl phthalate, BBP di-butyl phthalate, DBP di-2-ethylhexyl phthalate, DEHP) exposure of 10 Low-dose PAE exposure promoted the stem cell properties of BCSCs in a ΔNp63α- and SHH-dependent manner. The influence of low-dose exposure of PAEs and its relevance for the lowest observed effect concentrations requires further investigation, and the precise underlying mechanism needs to be further explored.

Exploring the cytotoxic effect and CDK-9 inhibition potential of novel sulfaguanidine-based azopyrazolidine-3,5-diones and 3,5-diaminoazopyrazoles.

Regarding the structural analysis of variable effective CDK-9 suppressors, we record the design and synthesis of two new sets of sulfaguanidine-based azopyrazolidine-3,5-diones and 3,5-diaminoazopyrazoles with expected anticancer and CDK-9 inhibiting activity. In the designed molecules, the pyrazole ring and sulphaguanidine fragment were linked together for the first time through diazo linkers as they are expected to enhance the anticancer activity and CDK degrading interaction. All derivatives have been estimated regarding their cytotoxic activity toward three tumor cells where CDK overexpression has been reported (HePG2, HCT-116, and MCF-7). Among these, four derivatives VII, VIII, X, and XIII exerted potent cytotoxicity against the chosen tumor cells presenting IC

Cationic lipid-conjugated bis-arylidene oxindole derivatives as broad-spectrum breast cancer-selective therapeutics.

Breast cancer is a heterogeneous malignancy with wide-ranging variations in therapeutic responses, overall survival etc. Major challenges for available chemotherapeutic agents in achieving clinical success are in maintaining systemic bio-distribution and avoiding non-specific adverse effects. Bis-arylidene oxindoles are estrogen receptor (ER)-selective bioactive molecules with moderate potency. In here, we have designed, synthesized and evaluated a series of twin aliphatic chain cationic lipid-conjugated bis-arylidene oxindole molecules with variations in nature of linker, lengths of carbon spacer and hydrophobic twin chains. We observed that among the various structural analogues, C8 twin-chain containing molecules, PGC8, S2C8 and S3C8 showed effective cancer cell-selective cytotoxicity in different cancer cell lines with an IC

Toward model-informed precision dosing for tamoxifen A population-pharmacokinetic model with a continuous CYP2D6 activity scale.

Tamoxifen is important in the adjuvant treatment of breast cancer. A plasma concentration of the active metabolite endoxifen of > 16 nM is associated with a lower risk of breast cancer-recurrence. Since inter-individual variability is high and > 20 % of patients do not reach endoxifen levels > 16 nM with the standard dose tamoxifen, therapeutic drug monitoring is advised. However, ideally, the correct tamoxifen dose should be known prior to start of therapy. Our aim is to develop a population pharmacokinetic (POP-PK) model incorporating a continuous CYP2D6 activity scale to support model informed precision dosing (MIPD) of tamoxifen to determine the optimal tamoxifen starting dose. Data from eight different clinical studies were pooled (539 patients, 3661 samples) and used to develop a POP-PK model. In this model, CYP2D6 activity per allele was estimated on a continuous scale. After inclusion of covariates, the model was subsequently validated using an independent external dataset (378 patients). Thereafter, dosing cut-off values for MIPD were determined. A joint tamoxifenendoxifen POP-PK model was developed describing the endoxifen formation rate. Using a continuous CYP2D6 activity scale, variability in predicting endoxifen levels was decreased by 37 % compared to using standard CYP2D6 genotype predicted phenotyping. After external validation and determination of dosing cut-off points, MIPD could reduce the proportion of patients with subtherapeutic endoxifen levels at from 22.1 % toward 4.8 %. Implementing MIPD from the start of tamoxifen treatment with this POP-PK model can reduce the proportion of patients with subtherapeutic endoxifen levels at steady-state to less than 5 %.

Phytoestrogens, novel dietary supplements for breast cancer.

While endocrine therapy is considered as an effective way to treat breast cancer, it still faces many challenges, such as drug resistance and individual discrepancy. Therefore, novel preventive and therapeutic modalities are still in great demand to decrease the incidence and mortality rate of breast cancer. Numerous studies suggested that G protein-coupled estrogen receptor (GPER), a membrane estrogen receptor, is a potential target for breast cancer prevention and treatment. It was also shown that not only endogenous estrogens can activate GPERs, but many phytoestrogens can also function as selective estrogen receptor modulators (SERMs) to interact GPERs. In this review, we discussed the possible mechanisms of GPERs pathways and shed a light of developing novel phytoestrogens based dietary supplements against breast cancers.

Novel framework for determining TPS-calculated doses corresponding to detector locations using 3D camera in in-vivo surface dosimetry.

To address the shortcomings of current procedures for evaluating the measured-to-planned dose agreement in in-vivo dosimetry (IVD), this study aimed to develop an accurate and efficient novel framework to identify the detector location placed on a patients skin surface using a 3D camera and determine the planned dose at the same anatomical position corresponding to the detector location. Breast cancer treatment was simulated using an anthropomorphic adult female phantom (ATOM 702-D CIRS, Norfolk, VA, USA). An optically stimulated luminescent dosimeter was used for surface dose measurements (MyOSLchip, RadPro International GmbH, Germany) at six IVD points. Three-dimensional surface imaging (3DSI) of the phantom with the detector was performed in the treatment position using a 3D camera. The developed framework, iSMART, was designed to import 3DSI and treatment planning data for determining the position of the IVD detectors in the 3D treatment planning DICOM image. The clinical usefulness of iSMART was evaluated in terms of accuracy and efficiency, for comparison with the results obtained using cone-beam computed tomography (CBCT) image guidance. The relative dose difference between the planned doses determined using iSMART and CBCT images displayed similar accuracies (within approximately ±2.0%) at all detector locations. The relative dose differences between the planned and measured doses at the six detector locations ranged from -4.8% to 3.1% for the CBCT images and -3.5% to 2.1% for iSMART. The total time required to read the planned doses at six detector locations averaged at 8.1 and 0.8 min for the CBCT images and iSMART, respectively. The proposed framework can improve the robustness of IVD analyses and aid in accurate and efficient evaluations of the measured-to-planned dose agreement.

Monolayer LDH Nanosheets with Ultrahigh ICG Loading for Phototherapy and Ca

Tumor recurrence and metastasis are the main causes of cancer mortality traditional chemotherapeutic drugs have severe toxicity and side effects in cancer treatment. To overcome these issues, here, we present a pH-responsive, self-destructive intelligent nanoplatform for magnetic resonancefluorescence dual-mode image-guided mitochondrial membrane potential damage (MMPD)photodynamic (PDT)photothermal (PTT)immunotherapy for breast cancer treatment with external near infrared (NIR) light irradiation. To do so, we construct multifunctional monolayer-layered double hydroxide (LDH) nanosheets (MICaP), co-loading indocyanine green (ICG) with ultrahigh loading content realized via electrostatic interactions, and calcium phosphate (Ca

Impact of a Biopsychosocial Screening Program on Clinical and Hospital-Based Outcomes in Cancer.

The integration of a biopsychosocial screening (BPS) program has been proposed by international agencies to better identify and effectively manage unmet needs among patients with cancer. We sought to evaluate the effect of a BPS program on hospital admissions and length of stay (LOS) among a diverse sample of patients with cancer and receiving treatment in Brazil. A retrospective analysis was performed from March 2020 to December 2021. Eligible patients were diagnosed with cancer and were receiving treatment at a private practice in Brazil. Clinical characteristics, participation in the BPS program, hospital admissions, reason, and LOS in hospital were evaluated. We compared the number of hospital admissions and LOS between groups (participation A total of 1,014 patients were included in the analysis. Baseline clinical characteristics were well balanced between groups (n 459 patients who participated and n 555 patients who did not). The median age of patients was 63 years. Breast and hematological cancers were the most common types of cancer 60% were diagnosed at an advanced disease stage. A smaller proportion of patients who participated in the BPS program were hospitalized compared with patients who did not participate (8% Engagement in a BPS program was associated with reduced hospital admissions and LOS. This study provides novel insight into the potential broader implications of BPS programs for clinical care systems. Future studies are needed to explore the mechanisms behind such associations.

Mn

Nanomedicine has the emerging potential to deliver advanced therapeutic strategies in the fight against triple-negative breast cancer (TNBC), a subcategory of breast cancer with a high degree of malignancy. As a type of fascinating drug carrier, nanoscale metal-organic frameworks (NMOF) have attracted much attention in biomedical fields for effective tumor therapy due to their unique properties, including tumor microenvironment (TME) stimuli-responsiveness, promising catalytic activity, and high biocompatibility. Nevertheless, it is still difficult to develop a precise co-delivery system that integrates highly effective photosensitizers, low toxicity, and hydrophobicity. In this study, PCN-224 was selected as the carrier to enable effective cancer therapy through light-activated reactive oxygen species (ROS) formation, and the PCN-224Mn

Accuracy and precision of contrast enhanced mammography versus MRI for predicting breast cancer size how good are they really

Toevaluate and compare the accuracy and precision of CEM versus MRI to predict the size of biopsy proven invasive breast cancer. 59 women with invasive breast cancer on needle biopsy underwent CEM and breast MRI. Two breast radiologists read each patients study, with access limited to one modality. CEM lesion size was measured using low-energy and recombined images and on MRI, the first post-contrast series. Extent of abnormality per quadrant was measured for multifocal lesions. Reference standards were size of largest invasive malignant lesion, invasive (PathInvasive) and whole (PathTotal). Pre-defined clinical concordance ±10 mm. Mean patient age 56 years, 42 (71%) asymptomatic. Lesions were invasive ductal carcinoma 40 (68%) with DCIS (3140) in 78%, multifocal in 12 (20%). Median lesion size was 17 mm (invasive) and 27 mm (total), range (5-125 mm). Lins concordance correlation coefficients for PathTotal 0.75 (95%CI 0.6, 0.84) and 0.71 (95%CI 0.56, 0.82) for MRI and CESM respectively. Mean difference for total size, 3% underestimated and 4% overestimated, and for invasive 41 and 50% overestimate on MRI and CESM respectively. Limits of agreement (LOA) for PathTotal varied from 60% under to a 2.4 or almost 3-fold over estimation. MRI was concordant with PathTotal in 36 (64%) cases compared with 32 (57%) for CESM. Both modalities concordant in 26 (46%) cases.Conclusion neither CEM nor MRI have sufficient accuracy to direct changes in planned treatment without needle biopsy confirmation. despite small mean differences in lesion size estimates using CEM or MRI, the 95% LOAs do not meet clinically acceptable levels.

Financial Toxicity Among Patients With Breast Cancer Worldwide A Systematic Review and Meta-analysis.

Financial toxicity (FT) is the negative impact of cost of care on financial well-being. Patients with breast cancer are at risk for incurring high out-of-pocket costs given the long-term need for multidisciplinary care and expensive treatments. To quantify the FT rate of patients with breast cancer and identify particularly vulnerable patient populations nationally and internationally. A systematic review and meta-analysis were conducted. Four databases-Embase, PubMed, Global Index Medicus, and Global Health (EBSCO)-were queried from inception to February 2021. Data analysis was performed from March to December 2022. A comprehensive database search was performed for full-text, English-language articles reporting FT among patients with breast cancer. Two independent reviewers conducted study screening and selection 462 articles underwent full-text review. A standardized data extraction tool was developed and validated by 2 independent authors study quality was also assessed. Variables assessed included race, income, insurance status, education status, employment, urban or rural status, and cancer stage and treatment. Pooled estimates of FT rates and their 95% CIs were obtained using the random-effects model. FT was the primary outcome and was evaluated using quantitative FT measures, including rate of patients experiencing FT, and qualitative FT measures, including patient-reported outcome measures or patient-reported severity and interviews. The rates of patients in high-income, middle-income, and low-income countries who incurred FT according to out-of-pocket cost, income, or patient-reported impact of expenditures during breast cancer diagnosis and treatment were reported as a meta-analysis. Of the 11 086 articles retrieved, 34 were included in the study. Most studies were from high-income countries (24 studies), and the rest were from low- and middle-income countries (10 studies). The sample size of included studies ranged from 5 to 2445 people. There was significant heterogeneity in the definition of FT. FT rate was pooled from 18 articles. The pooled FT rate was 35.3% (95% CI, 27.3%-44.4%) in high-income countries and 78.8% (95% CI, 60.4%-90.0%) in low- and middle-income countries. Substantial FT is associated with breast cancer treatment worldwide. Although the FT rate was higher in low- and middle-income countries, more than 30% of patients in high-income countries also incurred FT. Policies designed to offset the burden of direct medical and nonmedical costs are required to improve the financial health of vulnerable patients with breast cancer.

Screening mammography coverage and Decennial Plan for Cancer Control, Colombia 2014.

Estimate the coverage of screening mammograms in Colombia during 2014, as well as the performance in hours of equipment by the team and the number of teams required, to reach the goal of 70% coverage of screening mammography before the year 2021. A descriptive census study was carried out to characterize existing mammography equipment in the country. To this end, information was required from the Special Registry of Health Providers (REPS) and the operating licenses of mammography equipment processed before the territorial entities the information was processed, validated and analyzed through frequency distribution tables in the Microsoft Office Excel® program. The estimation of screening mammography coverage for the country based on the census of mammographers is 27.6% To reach the screening goal of screening mammography of 70% at the country level, a mammograph requires weekly 38.2 hours for screening, use 56.3% of total time for screening mammograms and acquire approximately 69 additional equipment to those screened in 2014. There are marked differences in these data at the department and regional level. At the country level, the estimation of screening mammography coverage is not good, it is necessary to improve the performance of mammography equipment, as well as acquire additional equipment for some regions accompanied by effective programmatic strategies in early detection of breast cancer. Estimar la cobertura de mamografías de tamización en Colombia durante el año 2014 así como el rendimiento en horas a emplear por equipo y el número de equipos requeridos, para alcanzar la meta de cobertura del 70% de mamografía de tamización antes del año 2021. Se realizó un estudio descriptivo para la caracterización de equipos de mamografía existentes en el país. Para ello, se requirió la información del Registro Especial de Prestadores de Salud (REPS) y la información de licencias de funcionamiento de equipos de mamografía tramitados ante los entes territoriales la información fue procesada, validada y analizada a través de tablas de distribución de frecuencias, en el programa Microsoft Office Excel®. La estimación de cobertura de mamografía de tamización para el país, con base en el censo de mamógrafos, es de 27.6% para alcanzar la meta de cobertura de mamografías de tamización del 70% a nivel país, un mamógrafo requiere emplear semanalmente 38.2 horas para tamización, el 56,3% de su tiempo total para mamografías de tamización y adquirir aproximadamente 69 equipos adicionales a los censados en el año 2014. Se muestran marcadas diferencias en estos datos a nivel departamental y regional. A nivel país, la estimación de cobertura de mamografía de tamización no es óptima y se requiere mejorar el rendimiento de los equipos de mamografía, así como adquirir equipos adicionales para algunas regiones, acompañado de estrategias programáticas eficaces en detección temprana de cáncer de mama.

Exercise tolerance and fatigue in women survivors of non-metastatic breast cancer.

Breast cancer is the most common type of cancer worldwide, and the leading cause of disability and death in young women in Latin America. One of the most common symptoms in this population is fatigue, reported by 70 to 100% of survivors. To describe the relationship between exercise tolerance and fatigue in women survivors of non-metastatic breast cancer. Cross-sectional descriptive study in 40 women between 18 and 65 years of age, from a database pertaining to a highly complex healthcare institution in the city of Cali, Colombia. The relationship between fatigue and exercise tolerance was identified using the Functional Assessment of Cancer Therapy FACT-F questionnaire and the 6-minute walk test (TC6M). 37.5% of the participants presented fatigue related to breast cancer 33% of women presented dyspnea at the end of the TC6M, 37.5% reported having lower limb fatigue (modified Borg) and 42.5% did not reach 80% of the predicted distance in the TC6M. A positive correlation (p 0.000) was found between fatigue and exercise tolerance in women survivors of non-metastatic breast cancer. El cáncer de mama es el más frecuente a nivel mundial y la principal causa de discapacidad y muerte en mujeres jóvenes en América Latina. Uno de los síntomas más comunes en esta población es la fatiga, reportada entre el 70 y 100% de mujeres sobrevivientes. Describir la relación entre tolerancia al ejercicio y la fatiga, en mujeres sobrevivientes de cáncer de mama no metastásico. Estudio descriptivo transversal en 40 mujeres entre 18 y 65 años, a partir de una base de datos de una institución de alta complejidad en la ciudad de Cali, Colombia. Se identificó la relación entre fatiga y tolerancia al ejercicio con el cuestionario The Functional Assessment of Cancer Therapy FACT-F y el test de caminata de los 6 minutos (TC6M). El 37,5% de las participantes presentaron fatiga relacionada con cáncer de mama 33% de las mujeres, disnea al final del TC6M 37,5%, fatiga en miembros inferiores (Borg modificada), y el 42,5% no alcanzó el 80% de la distancia predicha del TC6M. Se encontró una correlación positiva (p 0,000) entre fatiga y tolerancia al ejercicio en mujeres sobrevivientes de cáncer de mama no metastásico.

Cardiotoxicity and cancer prudential judgment in medical practice.

The objective of this paper is to propose a conceptual tool for consideration by medical professionals and cardiologists, based on the concept of prudential judgment or Aristotelian phronesis to confront the problems of cardiotoxicity resulting from cancer treatments. We start by analyzing the case of a young female patient who received two types of therapies the first with anthracyclines (adriamycin), which produces type I damage, as stated in the consensus of 2014 and the second treatment, one month later, with trastuzumab, an agent that produces type II damage not dependent on dose. In this case, the patient manifested acute cardiac insufficiency, with a decrease of LVEF to 28% on the echocardiogram and to 27% on magnetic resonance imaging. Reports have indicated that treatment with beta blockers and the suspension or decrease of the dose limits damage, but during preclinical stages. Awareness and early attention to subclinical damage have thus become extremely relevant to substantiate treatments based not only on clinical evidence but also on the ability of medical professionals to rely on prudential judgment--which moves away from the medical practices that are developed on a daily basis in order to influence and reduce the cases of irreversible heart failure known as cardiotoxicity.

Unmet needs in caregivers of patients with breast cancer dyadic perception.

To analyze the unmet needs of informal caregivers of women with breast cancer (CaMa) from a dyadic perspective. An exploratory, cross-sectional and qualitative study was carried out through in-depth interviews, completed in the Department of Breast Tumors of the National Cancer Institute of Mexico. Three dyads (informal primary caregivers and patients, respectively) were included. The analysis was performed using an inductive approach. Interpretive descriptive analysis was chosen as the most appropriate methodological design. The main unmet needs of the informal primary caregivers, perceived by the dyads, were psychological (such as the negative feelings caused by the mood changes of the patients) and informative (for example, the caregivers asked for information related to side effects and how to care and that the writing information use colloquial terms). The unmet needs are the result of taking care, the level of affective commitment they have with the patient and the lack of training for care. The study highlights the relevance of planning interventions from a dyadic perspective. Analizar las necesidades insatisfechas de los cuidadores informales de mujeres con cáncer de mama desde una perspectiva diádica. Se realizó un estudio exploratorio, transversal y cualitativo mediante entrevistas en profundidad, completado en el Departamento de Tumores de Mama del Instituto Nacional de Cancerología de México. Se incluyeron tres díadas (cuidadores primarios informales y pacientes, respectivamente). El análisis se realizó utilizando un enfoque inductivo. El análisis descriptivo interpretativo fue elegido como el diseño metodológico más apropiado. Las principales necesidades insatisfechas de los cuidadores primarios informales percibidas por las díadas fueron psicológicas (como los sentimientos negativos causados por los cambios de humor de los pacientes) e informativas (por ejemplo, sobre efectos secundarios de los tratamientos y sobre la realización de cuidados, y que la redacción de la información utilizara términos coloquiales, etc.). Las necesidades no satisfechas son resultado de realizar el cuidado, del nivel de compromiso afectivo que tienen con el paciente y de la falta de capacitación para el cuidado. El estudio destaca la relevancia de planear intervenciones desde una perspectiva diádica.

Retroauricular Single-Site Endoscopic Thyroidectomy-A Balanced Endoscopic Approach for Thyroid Excision.

This article discusses how retroauricular single-site endoscopic thyroidectomy is performed and compares it with transaxillary, transareolar, retroauricular hairline, and transoral endoscopic thyroidectomy vestibular approaches.

Fatty acid synthase as a new therapeutic target for HER2-positive gastric cancer.

Trastuzumab is an HER2-specific agent approved as the gold-standard therapy for advanced HER2-positive (HER2) gastric cancer (GC), but the high rate and rapid appearance of resistance limit its clinical efficacy, resulting in the need to identify new vulnerabilities. Defining the drivers influencing HER2 cancer stem cell (CSC) maintenancesurvival could represent a clinically useful strategy to counteract tumor growth and therapy resistance. Accumulating evidence show that targeting crucial metabolic hubs, as the fatty acid synthase (FASN), may be clinically relevant. FASN protein and transcript expression were examined by WB and FACS and by qRT-PCR and GEP analyses, respectively, in trastuzumab-sensitive and trastuzumab-resistant HER2 GC cell lines cultured in adherent (2D) or gastrosphere promoting (3D) conditions. Molecular data were analyzed in silico in public HER2 GC datasets. The effectiveness of the FASN inhibitor TVB3166 to overcome anti-HER2 therapy resistance was tested in vitro in gastrospheres forming efficiency bioassays and in vivo in mice bearing trastuzumab-resistant GC cells. We compared the transcriptome profiles of HER2 GC cells cultured in 2D versus 3D conditions finding a significant enrichment of FASN in 3D cultures. FASN upregulation significantly correlated with high stemness score and poor prognosis in HER2 GC cases. TVB3166 treatment significantly decreased GCSCs in all cell targets. HER2 and FASN cotargeting significantly decreased the capability to form gastrospheres versus monotherapy and reduced the in vivo growth of trastuzumab-resistant GC cells. Our findings indicate that cotargeting HER2 and FASN increase the benefit of anti-HER2 therapy representing a new opportunity for metabolically combating trastuzumab-resistant HER2 GC.

The use of gabapentinoids and opioids and risk of developing opioid-induced respiratory depression among older breast cancer survivors with neuropathic pain.

To estimate the combined effect of gabapentinoid and opioid therapy compared to opioid monotherapy on the risk of developing opioid-induced respiratory depression among breast cancer survivors with neuropathic pain. A nested case-control study of Medicare female breast cancer survivors with neuropathic pain receiving both opioids and gabapentinoids, opioid monotherapy, gabapentinoid monotherapy, and none of these drugs was conducted using SEER-Medicare between 2007 and 2015. Cases were survivors with respiratory depression and were matched with controls on the event date (± 1 year), age at diagnosis (± 5 years), and stage at diagnosis. Exposure to opioids and gabapentinoids was assessed 120 days before the event date. Conditional logistic regression was used to assess the impact of exposure among cases and controls. A total of 657 cases and 11,471 controls were identified. After matching, 656 cases and 5612 controls were retained, and cases were more likely to be diagnosed with mental health disorders (24.4% vs 10.5%, p < 0.0001) than controls. In the primary adjusted analysis, combined opioids and gabapentin use were associated with an increased risk of respiratory depression compared to opioid monotherapy (Adj. OR 1.513 95% CI 1.473-2.350). Additionally, under secondary analysis, combined opioids and gabapentin use were associated with an increased risk of respiratory depression compared to receiving neither of these classes. (Adj. OR 1.595 95% CI 1.050-2.421). There is a need for dose titration strategies of gabapentinoids and caution when co-prescribing opioids and gabapentinoids in older cancer survivors.

Oocyte vitrification for fertility preservation following COS does not delay the initiation of neoadjuvant chemotherapy for breast cancer compared to IVM.

The objective of the present study was to evaluate whether oocyte vitrification following controlled ovarian stimulation (COS) for fertility preservation (FP) delays the initiation of neoadjuvant chemotherapy (NAC) for breast cancer (BC) as compared to in vitro maturation (IVM). We performed a retrospective cohort study including all BC patients eligible for oocyte vitrification following COS or in vitro maturation (IVM) before initiation of NAC between January 2016 and December 2020. The inclusion criteria were female patients aged between 18 and 40, with confirmed non metastatic BC, with indication of NAC, who have had oocyte retrieval for FP after COS, or IVM - cryopreservation of ovarian tissue (OTC). Various time points related to cancer diagnosis, FP, or chemotherapy were obtained from a medical record review. A total of 197 patients with confirmed BC who had oocyte retrieval following COS (n 57) or IVM - OTC (n 140) for FP prior to NAC were included. Overall, the average time from cancer diagnosis to chemotherapy start was similar between patients having undergone COS or IVM before oocyte vitrification (37.3 ± 13.8 vs. 36. 8 ± 13.5 days p 0.89). The indication of NAC for BC should not be considered as an impediment to urgent COS for oocyte vitrification for FP.

Melatonin and Health Insights of Melatonin Action, Biological Functions, and Associated Disorders.

Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin production and to lesser extent by retina, lymphocytes, bone marrow, gastrointestinal tract, and thymus. Melatonin as a neurohormone is released into circulation wherein it penetrates all tissues of the body. Melatonin synthesis and secretion is supressed by light and enhanced by dark. Melatonin mostly exerts its effect through different pathways with melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) being the predominant type of receptor that are mainly expressed by many mammalian organs. Melatonin helps to regulate sleep patterns and circadian rhythms. In addition, melatonin acts as an antioxidant and scavenges excessive free radicals generated in the body by anti-excitatory and anti-inflammatory properties. A multiple array of other functions are displayed by melatonin that include oncostatic, hypnotic, immune regulation, reproduction, puberty timing, mood disorders, and transplantation. Deficiencies in the production or synthesis of melatonin have been found to be associated with onset of many disorders like breast cancer and neurodegenerative disorders. Melatonin could be used as potential analgesic drug in diseases associated with pain and it has quite promising role there. In the past century, a growing interest has been developed regarding the wide use of melatonin in treating various diseases like inflammatory, gastrointestinal, cancer, mood disorders, and others. Several melatonin agonists have been synthesized and are widely used in disease treatment. In this review, an effort has been made to describe the biochemistry of melatonin along with its therapeutic potential in various diseases of humans.

High-Risk Breast Lesions Diagnosed by Ultrasound-Guided Vacuum-Assisted Excision.

The aim of this study was to analyze the role of ultrasound-guided vacuum-assisted excision (US-guided VAE) in the treatment of high-risk breast lesions and to evaluate the clinical and US features of the patients associated with recurrence or development of malignancy. Between April 2010 and September 2021, 73 lesions of 73 patients underwent US-guided VAE and were diagnosed with high-risk breast lesions. The incidence of recurrence or development of malignancy for high-risk breast lesions was evaluated at follow-up period. The clinical and US features of the patients were analyzed to identify the factors affecting the recurrence or development of malignancy rate. Only benign phyllodes tumors on US-guided VAE showed recurrences, while other high-risk breast lesions that were atypical ductal hyperplasia (ADH), lobular neoplasia (atypical lobular hyperplasialobular carcinoma in situ), radial scar, and flat epithelial atypia did not show recurrences or malignant transformation. The recurrence rate of the benign phyllodes tumor was 20.8% (524) in a mean follow-up period of 34.3 months. The recurrence rate of benign phyllodes tumor with distance from nipple of less than 1 cm was significantly higher than that of lesions with distance from nipple of more than 1 cm (75% vs. 10%, p < 0.05). Benign phyllodes tumors without concurrent breast cancer could be safely followed up instead of surgical excision after US-guided VAE when the lesions were classified as BI-RADS 3 or 4A by US.

Targeting senescence as a therapeutic opportunity for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is associated with an elevated risk of recurrence and poor prognosis. Historically, only chemotherapy was available as systemic treatment, but immunotherapy and targeted therapies currently offer prolonged benefits. TNBC is a group of diseases with heterogeneous treatment sensitivity, and resistance is inevitable and early for a large proportion of the intrinsic subtypes. Although senescence induction by anticancer therapy offers an immediate favourable clinical outcome once the rate of tumour progression reduces, these cells are commonly dysfunctional and metabolically active, culminating in treatment-resistant repopulation associated with worse prognosis. This heterogeneous response can also occur without therapeutic pressure, in response to damage or oncogenic stress, playing a relevant role in the carcinogenesis. Remarkably, there is pre-clinical and exploratory clinical evidence to support a relevant role of senescence in treatment resistance. Therefore, targeting senescent cells has been a scientific effort in many malignant tumours using a variety of targets and strategies, including increasing pro-apoptotic and decreasing anti-apoptotic stimuli. Despite promising, there are some challenges to applying this technology, including the best schedule of combination, assessment of senescence, specific vulnerabilities, and the best clinical scenarios. This review provides an overview of senescence in TNBC with focus on future-proofing senotherapy strategies.

Age-related differences in cancer relative survival in the US a SEER-18 analysis.

Cancer survival has improved since the 1990s, but to different extents across age groups, with a disadvantage for older adults. We aimed to quantify age-related differences in relative survival (RS - one-year, and one-year conditioning on surviving one year) for 10 common cancer types by stage at diagnosis. We used data from 18 United States Surveillance Epidemiology and End Results cancer registries and included cancers diagnosed in 2012-2016 followed until December 31, 2017. We estimated absolute differences in RS between the 50-64 age group and the 75-84 age group. The smallest differences were observed for prostate and breast cancers (1.8%-points 95% confidence interval (CI)1.5-2.1 and 1.9%-points 95%CI 1.5-2.3, respectively). The largest was for ovarian cancer (27%-points, 95%CI 24-29). For other cancers, differences ranged between 7 (95%CI 5-9, esophagus) and 18%-points (95%CI 17-19, pancreas). Except for pancreatic cancer, cancer type and stage combinations with very high (>95%) or very low (<40%) one-year RS tended to have smaller age-related differences in survival than those with mid-range prognoses. Age-related differences in one-year survival conditioning on having survived one-year were small for most cancer and stage combinations. The broad variation in survival differences by age across cancer types and stages, especially in the first year, age-related differences in survival are likely influenced by amenability to treatment. Future work to measure the extent of age-related differences that are avoidable, and identify how to narrow the survival gap, may have most benefit by prioritizing cancers with relatively large age-related differences in survival (e.g., stomach, esophagus, liver and pancreas).

The Impact of Breast Cancer Type, Staging, and Treatment on Vascular Complications of Immediate Free-Flap Breast Reconstruction.

Patients with advanced cancer staging have a greater risk of developing venous thromboembolism than noncancer patients. The impact of breast cancer stage and treatment on outcomes after autologous free-flap breast reconstruction (ABR) is not well-established. The objective of this retrospective study is to determine the impact of breast cancer characteristics, such as cancer stage, hormone receptor status, and neoadjuvant treatments, on vascular complications of ABR. A retrospective review was conducted examining patients who underwent ABR from 2009 to 2018. Breast cancer stage, cancer types, hormone receptor status, and treatments were collected in addition to demographic data. Intraoperative vascular concerns, postoperative vascular concerns, and flap loss were analyzed. Univariate analysis and fixed-effects models were used to associate breast cancer characteristics with outcomes. Neoadjuvant hormone therapy was associated with increased risk for intraoperative vascular concern (odds ratio, 1.059 P 0.0441). Neoadjuvant trastuzumab was associated with decreased risk of postoperative vascular concern (odds ratio, 0.941 P 0.018). Breast cancer stage, somatic genetic mutation, receptor types, neoadjuvant chemotherapy, and neoadjuvant radiation had no effect on any vascular complications of ABR. Autologous free-flap breast reconstruction is a reliable reconstructive option for patients with all stages and types of breast cancer. There is potentially increased risk of intraoperative microvascular compromise in patients who have neoadjuvant hormone therapy. Trastuzumab is potentially protective against postoperative microvascular compromise. Patients should feel confident that, despite higher stage cancer, they can pursue their desired reconstructive option without fear of vascular compromise.

Test performance metrics for breast, cervical, colon and lung cancer screening a systematic review.

Multiple quality metrics have been recommended to ensure consistent, high-quality execution of screening tests for breast, cervical, colorectal and lung cancers. However, minimal data exist evaluating the evidence base supporting these recommendations and the consistency of definitions and concepts included within and between cancer types. We performed a systematic review for each cancer type using MEDLINE, Embase and CINAHL from 2010 to April 2020, to identify guidelines from screening programs or professional organizations containing quality metrics for tests used in breast, cervical, colorectal and lung cancer screening. We abstracted metrics definitions, target performance levels, and related supporting evidence for test completeness, adequacy (sufficient visualization or collection), accuracy, and safety. We identified 11 relevant guidelines with 20 suggested quality metrics for breast cancer, 5 guidelines with 9 metrics for cervical cancer, 13 guidelines with 18 metrics for colorectal cancer, and 3 guidelines with 7 metrics for lung cancer. These included 54 metrics related to adequacy (6), test completeness (3), accuracy (33), and safety (12). Target performance levels were defined for 30 metrics (56%). Ten (19%) were supported by evidence, all from breast and colorectal cancer, with no evidence cited to support metrics from cervical and lung cancer screening. Considerably more guideline-recommended test performance metrics exist for breast and colorectal cancer screening than cervical or lung cancer. The domains covered are inconsistent among cancers and few targets are supported by evidence. Clearer evidence-based domains and targets are needed for test performance metrics. PROSPERO 2020 CRD42020179139.

Abbreviated Versus Full-Protocol MRI for Breast Cancer Neoadjuvant Chemotherapy Response Assessment Diagnostic Performance by General and Breast Radiologists.

Predicting Upgrade of Ductal Carcinoma in Situ to Invasive Cancer at Breast Surgery With Ultrafast Imaging.

Designing of new tetrahydro-β-carboline-based ABCG2 inhibitors using 3D-QSAR, molecular docking, and DFT tools.

Human ATP-binding cassette superfamily G member 2 (ABCG2) protein is a member of the ABC transporter family, which is responsible for multidrug resistance (MDR) in cancerous cells. MDR reduces the effectiveness of chemotherapy in breast cancer, which is one of the leading causes of death in women globally. MDR in cancer cells is one of the immediate signs of progression of resistance thus, various anticancer drugs can be designed. To reduce MDR, we utilized the tetrahydro-β-carboline (THβC) compound library. We accomplished a three-dimensional quantitative structure-activity relationship (3D-QSAR), scaffold hopping to design a new library of compounds of THβC, and further molecular docking, induced-fit docking (IFD), molecular mechanics energies combined with generalized born and surface area continuum solvation (MM-GBSA), drug-like features, ADMET properties, and density functional theory (DFT) studies were performed. From these studies, the best 3D-QSAR model (r

KLF14miR-1283TFAP2C axis inhibits HER2-positive breast cancer progression via declining tumor cell proliferation.

MiR-1283 has been identified as a tumor suppressor in some malignancies. Whereas, the role of miR-1283 in HER2-positive (HER2) breast cancer, particularly its role in regulating cell proliferation, one of the most significant features of tumor progression, is unclear. The related microRNA screened by the breast cancer sample GSE131599 dataset were detected in HER2 breast cancer tissues and cell lines. Then, the obtained miR-1283 was overexpressed in SKBR3 and BT-474 cells followed by relevant functional assays concerning cell proliferation and apoptosis. The xenograft mouse model was induced and the effect of miR-1283 on tumor growth and cell proliferation was examined. The target of miR-1283 and the transcription factor regulating miR-1283 were predicted and identified. Finally, the influence of transcription factor KLF14 on cell proliferation and apoptosis was investigated. An integrated analysis confirmed that miR-1283 expression was significantly decreased in HER2 breast cancer tissues. Also, by q-RT-PCR detection, miR-1283 expression was markedly reduced in HER2 breast cancer tissues and cell lines. The miR-1283 overexpression prevented the proliferation and enhanced apoptosis of HER2 breast cancer cells, as well as inhibited tumor growth. Mechanistically, miR-1283 inhibited TFAP2C expression by targeting the 3-untranslated regions of TFAP2C messenger RNA, and the KLF14 enhanced miR-1283 level via binding to its promoter. The result subsequently confirmed the KLF14miR-1283 signaling suppressed cell proliferation in HER2 breast cancer. Our results suggested that the KLF14miR-1283TFAP2C axis inhibited HER2 breast cancer progression, which might provide novel insight into mechanical exploration for this disease.

Identification of HER2 inhibitors from curcumin derivatives using combination of

Breast cancer remains a major world health challenge in women. Some Breast cancers are human epidermal growth factor receptor 2 (HER2) positive. Since this protein promotes the growth of cancer cells, it remains a therapeutic target for novel drugs. This study uses

Psychotraumatization and Treatment of Posttraumatic Stress Disorder in Patients with Newly Diagnosed Breast Cancer.

According to DSM-IV cancer is a stress event with influence on development of posttraumatic stress disorder (PTSD) but in many crysis, sometimes it is hard to define concrete stressor. PTSD ussually appears in the first three moths after trauma, but can be delayed for months or years. It is hard to diferentiate psychiatric states and specific treatment methods have different impact on PTSD symptoms. Aim was to evaluate impact of different psychiatric treatment methods on development and treatment of PTSD in patients with newly diagnosed breast cancer. Sample consisted of 120 women with breast cancer during radiotherapy on Department for Oncology on University Hospital Osijek. Patients were divided in four groups and each group was treated with different psychiatric treatment method (psychopharmacology andor psychotherapy, control group with no treatment). We used detailed clinical examination with psychiatric interview (DSM-IV criteria), specially structured non-standardized questionnaire for ethyological factors and LASC for PTSD. Data was analyzed by adequate statistical methods. Although most of participants didnt have complite PTSD, some symptoms were present, and in some women were intensive, so they should be the main group for psychiatric tretment. We found falling values of PTSD symptoms in group treated with combination of psychotherapy and psychopharmacology and raising values in a control group. They are at risk of developing whole clinical picture of PTSD during time. Our results prove the need for constant evaluation of PTSD development during oncology treatment and positive effects of combined psychiatric treatment on reduction of PTSD symptoms.

SREKA-targeted liposomes for highly metastatic breast cancer therapy.

Chemotherapy is still a leading therapeutic approach in various tumor types that is often accompanied by a poor prognosis because of metastases. PEGylated liposomes with CREKA targeting moiety are well-known therapeutic agents, especially in highly metastatic experimental models. CREKA specifically targets tumor-associated ECM, which is present at the primary, as well as metastatic tumor sites. To better understand the function of the targeting moieties, we decided to design various liposome formulations with different amounts of targeting moiety attached to their DSPE-PEG molecules. Moreover, a new tumor-homing pentapeptide (SREKA) was designed, and a novel conjugation strategy between SREKA and DSPE-PEGs. First, the

Awareness and knowledge of risk factors associated with oral cancer among military personnel in Nigeria.

The military lifestyle has been reported to increase the risk of this population group to the development of oral cancer. This study aimed to determine the awareness and knowledge of oral cancer in a population of soldiers to acquire data for establishing an educational program for units of the Nigerian Army in oral cancer prevention and monitoring. The study was conducted in the dental center of 82 Division Military Hospital, Nigerian Army, Enugu, Nigeria. A cross-sectional survey was performed using a pre-tested self-administered questionnaire. Questions relating to oral cancer awareness, knowledge of causes, and relationship to certain habits, treatment options, and desirability of screening opportunities for oral cancer were asked. Soldiers attending the military hospital, dental center, were chosen randomly for the study. Three hundred soldiers were surveyed. The mean age of those surveyed was 37.5 and had spent an average of 11-15 years in the Army. The majority of the soldiers (80.7%) have heard of cancer the types most known were breast (75%), skin (30%), and lung cancer (28.3%). Of the 300 soldiers surveyed, 15.3% knew about oral cancer, with 41.3% of these able to identify cigarette smoking and (26%) alcohol consumption as possible risk factors associated with oral cancer. The majority believed that cancer was caused by some form of supernatural phenomenon. Oral cancer awareness is low among soldiers in the Nigerian Armed Forces, and strategies to increase awareness should be developed.

Polypropylene sulphide coating on magnetic nanoparticles as a novel platform for excellent biocompatible, stimuli-responsive smart magnetic nanocarriers for cancer therapeutics.

Magnetic nanoparticle (MNP) delivery systems are promising for targeted drug delivery, imaging, and chemo-hyperthermia of cancer however, their uses remain limited primarily due to their toxicity associated with reactive oxygen species (ROS) generation, targeted delivery, and biodegradation. Attempts employing polymer coatings to minimize the toxicity, along with other challenges, have had limited success. We designed a novel yet generic one-for-all polypropylene sulphide (PPS) coated magnetic nano-delivery system (80 ± 15 nm) as a multi-faceted approach for significant biocompatibility improvement, loading of multiple drugs, ROS-responsive delivery, and combined chemo-hyperthermia therapy for biomedical applications. Three distinct MNP systems (15 ± 1 nm) were fabricated, coated with PPS polymer, and investigated to validate our hypothesis and design. Simultaneous degradation of MNPs and PPS coatings with ROS-scavenging characteristics boosted the biocompatibility of MNPs 2-3 times towards non-cancerous fibroblasts (NIH3T3) and human epithelial cells (HEK293). In an alternating magnetic field, PPS-MNPs (MnFe) had the strongest heating characteristics (SAR value of 240 W g

Pertuzumab in Combination with Trastuzumab and Docetaxel in the Neoadjuvant Treatment for HER2-Positive Breast Cancer.

This study aims to assess safety and effectiveness of pertuzumab in combination with trastuzumab and docetaxel in the neoadjuvant treatment (NeoT) of HER2-positive breast cancer. Two consecutive retrospective cohorts ( The 2012-2015 cohort was older (median 53 years), with locally advanced tumors (48.1%), mostly hormone receptor positive (59.3%). The 2015-2017 cohort was younger (median 43 years) with 60% operable tumors. Pathologic complete response (pCR) improved in the second cohort, while maintaining a good safety profile and tolerability. Clinical staging ( Further research with larger samples and longer follow-up is needed to understand the clinical differences. Clinical effectiveness of treatment should also be measured through overall and progression-free survival.

The Impact of Travel Distance and Income on Breast Reconstruction after Mastectomy in a Rural Population.

Factors that influence breast reconstruction after mastectomy have been previously examined in national databases. The purpose of this study was to determine the impact of patient travel distance and income on breast reconstruction after mastectomy in a rural population. Retrospective review of mastectomy patients from 2017 to 2021 was performed from our prospectively enrolled tumor registry. Analysis included frequencies and percentages, descriptive statistics, In total, 462 patients were included. Median BMI was 27.6 kgm Travel distance did not significantly impact reconstruction rates after mastectomy, while household income did on univariable analysis. Studies at an institutional or regional level remain valuable, especially in populations that may not be accurately represented in larger database studies. Our findings highlight the importance of patient education, resource allocation, and multidisciplinary approach to breast cancer care, especially in the rural setting.

Identification and verification of immune-related gene prognostic signature based on ssGSEA for breast cancer.

Breast cancer (BC) is the most common cancer in women worldwide and has a high mortality rate. The fact that the tumor microenvironment affects clinical outcomes of all types of cancers underlines the involvement of various immune-related genes (IRGs). Therefore, this study aimed to establish an IRGs-based signature for the prognosis of BC patients. In this study, 12 immune cell infiltrating degrees in 1,102 BC cases from The Cancer Genome Atlas (TCGA) database were assessed, and RNA-sequencing (RNA-seq) data of these samples were analyzed by single-sample gene set enrichment analysis (ssGSEA). Based on the results, high, low, and middle immune infiltrating clusters were constructed. A total of 138 overlapped differentially expressed genes (DEGs) were identified in the high and low infiltrating clusters, as well as in normal and BC samples. Univariate Cox regression and LASSO analyses were also performed. Furthermore, GSEA suggested some highly enriched pathways in the different immune infiltrating clusters, leading to a better understanding of potential mechanisms of immune infiltration in BC. Finally, 19 immune-related genes were identified that could be utilized as a potential prognostic biomarker for BC. Kaplan-Meier plot and ROC curve, univariate as well as multivariate Cox analyses were carried out, which suggested that the 19-IRG-based signature is a significant prognosis factor independent of clinical features. Based on the analysis of protein-protein interactions (PPI), the three hub genes were identified. These results provide a new method to predict the prognosis and survival of BC based on the three genes features.

Radiation-induced morphea of the breast-A case series.

Radiation-induced morphea (RIM) is a rare but recognized late complication of radiotherapy. It was first described in 1905, not long after the initial discovery of X-rays by Roentgen. Characterized by the deposition of excess collagen in the dermis, it results in thickening of the skin. Its frequency is approximately 2 in 1000. We present a series of three cases involving patients receiving radiotherapy treatment for breast cancer, each of which subsequently developed RIM. Because of its rarity, RIM is often misdiagnosed as infection or metastatic disease. This can lead to delayed diagnosis and treatment, leading to poorer outcomes such as chronic pain issues. Early dermatological involvement and tissue sampling to examine histopathological features can avoid this, leading to better care and improved results. A variety of treatment options are available, ranging from topical to systemic, with early induction more likely to result in a positive response.

Long-Term Yogic Intervention Improves Symptomatic Scale and Quality of Life by Reducing Inflammatory Cytokines and Oxidative Stress in Breast Cancer Patients Undergoing Chemotherapy andor Radiotherapy A Randomized Control Study.

Inflammation has been associated with tumor proliferation and metastasis in breast cancer. Yoga is an ancient therapy that helps in reducing inflammation and improves the patients quality of life (QoL) and fatigue. In the current study, we investigated the effects of long-term yogic intervention at different time points on the level of inflammatory cytokines and oxidative stress, along with the symptomatic scale and QoL in stage IIIII breast cancer patients. Ninety-six stage IIIII breast cancer patients receiving chemotherapy andor radiotherapy were enrolled and divided into two groups, non-yoga (Group I) and yoga (Group II). Participants in Group II practiced yoga five days per week for 48 weeks. The European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ30) was used to measure the QoL and symptomatic scale. Serum levels of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ) and granulocyte macrophage colony-stimulating factor (GM-CSF), and oxidative stress markers, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and nitric oxide (NO) were measured at baseline, 16, 32, and 48 weeks in both groups. Yoga significantly (p<0.05) reduced the level of IFN-γ, TNF-α, and MDA and improved QoL (p<0.001) and symptomatic scale (p<0.05) in Group II patients compared to Group I. NO was upregulated in Group I whereas in Group II, it was neither decreased nor increased. These findings suggest that yoga may reduce levels of inflammatory cytokines and improve QoL and symptomatic scale in breast cancer patients receiving chemotherapy andor radiotherapy. Yoga can be an important additional therapy during cancer treatments to cope with treatment side effects including fatigue, depression, and immunological profile, which directly affects the patients quality of life.

Prognostic role of immune environment in luminal B early breast cancer.

The importance of the immune microenvironment in triple negative and HER2-amplified breast cancer (BC) is well-established less is known about the immune environment in luminal breast cancers. We aimed to assess for the impact of immune biomarkers on BC outcome in a group of luminal B patients with archived tissue and annotated clinical information. Patients with early breast cancer (EBC) treated in a single institution over a 14-year period, with prospectively collected data were included. Luminal B EBC patients were identified and defined into three cohorts A grade 2 or 3, ER PR positive, HER2-negative B Any grade, ER positive, PR and HER2-negative (Ki67 ≥ 14% in cohorts A B) and C Any grade, ER or PR positive, HER2-positive. Within each cohort, patients with a relapsed BC event (R) were compared on a 11 basis with a control patient (C) who remained disease-free, balanced for key characteristics in an effort to balance the contribution of each clinical group to outcome. Archival breast, involved and uninvolved axillary nodes were assessed by immunohistochemistry for biomarkers identifying effector and suppressor immune cells, and compared between R and C. In total, 120 patients were included (80, 22, and 18 patients in cohorts A, B, and C, respectively). R were 1.5 years older (p 0.016), with all other characteristics being balanced. Overall, there were no statistically significant differences in immune biomarkers in breast or nodal tissue of R and C. However, there was a trend toward higher levels of TILs in breast tumors of C, while GAL-9 was consistently expressed on lymphocytes and tumor cells in all breast and nodes of C and was absent from all tissues of R. These trends in checkpoint molecule expression deserve further research.

Breakthroughs in the Systemic Treatment of HER2-Positive AdvancedMetastatic Gastric Cancer From Singlet Chemotherapy to Triple Combination.

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidineplatinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC trastuzumab emtansine T-DM1), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

Shining the light on mesenchymal stem cell-derived exosomes in breast cancer.

In women, breast cancer (BC) is the second most frequently diagnosed cancer and the leading cause of cancer death. Mesenchymal stem cells (MSCs) are a subgroup of heterogeneous non-hematopoietic fibroblast-like cells that have the ability to differentiate into multiple cell types. Recent studies stated that MSCs can migrate into the tumor sites and exert various effect on tumor growth and development. Multiple researches have demonstrated that MSCs can favor tumor growth, while other groups have indicated that MSCs inhibit tumor development. Emerging evidences showed exosomes (Exo) as a new mechanism of cell communication which are essential for the crosstalk between MSCs and BC cells. MSC-derived Exo (MSCs-Exo) could mimic the numerous effects on the proliferation, metastasis, and drug response through carrying a wide scale of molecules, such as proteins, lipids, messenger RNAs, and microRNAs to BC cells. Consequently, in the present literature, we summarized the biogenesis and cargo of Exo and reviewed the role of MSCs-Exo in development of BC.

Solubility of palbociclib in supercritical carbon dioxide from experimental measurement and Peng-Robinson equation of state.

Palbociclib is a poorly water-soluble medicine which acts against metastatic breast cancer cells. Among various techniques to improve the solubility of this medicine, applying supercritical technologies to produce micro- and nano-sized particles is a possible option. For this purpose, extraction of solubility data is required. In this research, the solubility of palbociclib in supercritical carbon dioxide (ScCO

Cancer in pregnancy breast cancer.

Breast cancer is the most common malignancy in women, and for women under 40, it is the leading cause of cancer-related deaths. A specific type of breast cancer is pregnancy-associated breast cancer, which is diagnosed during pregnancy, the first-year postpartum, or during lactation. Pregnancy-associated breast cancer is seen in 31000 pregnancies and is increasing in incidence as women delay pregnancy. This type of breast cancer is more aggressive, and not infrequently, there is a delay in diagnosis attributed to physiologic changes that occur during pregnancy and a lack of awareness among physicians. In this review, we discuss the demographics of pregnancy-associated breast cancer, provide differential considerations, and illustrate the multimodality imaging features to bring attention to the radiologist about this aggressive form of breast cancer.

Ferroptosis, Acyl Starvation, and Breast Cancer.

To maintain their growth rate, cancer cells must secure a supply of fatty acids, which are necessary for building cell membranes and maintaining energy processes. This is one of the reasons why tissues with intensive fatty acid metabolism, such as the mammary gland, are more likely to develop tumors. One natural or induced defense process against cancer is ferroptosis, which interferes with normal fatty acid metabolism. This leads to the oxidation of polyunsaturated fatty acids, which causes a rearrangement of the metabolism and damages cell membranes. As a consequence of this oxidation, there is a shortage of normal polyunsaturated fatty acids, which disturbs the complicated metabolism of fatty acids. This imbalance in metabolism, resulting from the deficiency of properly structured fatty acids, is called, by these authors, acyl starvation. When cancer cells are exposed to alternating hypoxia and reoxygenation, they often develop resistance to neoadjuvant therapies. Blocking the stearoyl-CoA desaturase - fatty acid-binding protein 4 - fatty acid translocase axis appears to be a promising pathway in the treatment of breast cancer. On the one hand, the inhibition of desaturase leads to the formation of toxic phospholipid hydroperoxides in ferroptosis, whereas on the other hand, the inhibition of fatty acid-binding protein 4 and translocase leads to a reduced uptake of fatty acids and disruption of the cellular transport of fatty acids, resulting in intracellular acyl starvation. The disruption in the metabolism of fatty acids in cancer cells may augment the effectiveness of neoadjuvant therapy. SIGNIFICANCE STATEMENT Regulation of the metabolism of fatty acids in cancer cells seems to be a promising therapeutic direction. Studies show that the induction of ferroptosis in cancer cells, combined with use of neoadjuvant therapies, effectively inhibits the proliferation of these cells. We link the process of ferroptosis with apoptosis and SCD1-FABP4-CD36 axis and propose the term acyl starvation for the processes leading to FA deficiency, dysregulation of FA metabolism in cancer cells, and, most importantly, the appearance of incorrect proportions FAs.

Effects of self-disclosure and resilience on reproductive concern in patients of childbearing age with breast cancer a cross-sectional survey study.

To assess reproductive concerns in patients of childbearing age with breast cancer and examine the relationship between self-disclosure, resilience and reproductive concerns. Cross-sectional survey. Five tertiary first-class general hospitals in Sichuan Province, Southwest China. A total of 319 patients with breast cancer of reproductive age who were hospitalised in the breast oncology department participated in this study. Primary outcomes were the relationship between resilience, self-disclosure and reproductive concerns, and mediating effect analyses. Secondary outcomes included the status of reproductive concerns. The model accounted for 39.1% of the variance in reproductive concerns. Self-disclosure had a direct negative effect on reproductive concerns (β -0.371, p0.001). Resilience had a direct negative effect on reproductive concerns (β -0.349, p0.001) and a direct positive effect on self-disclosure (β0.507, p0.001). Furthermore, self-disclosure partially mediated the relation between resilience and reproductive concerns (β -0.177 SE0.041 95% CI -0.261 to -0.104 p<0.050), with a bootstrap of 10 000 samples. The findings suggest that self-disclosure and resilience may ease reproductive concern. Therefore, self-disclosure education and resilience-oriented interventions should be provided to patients of childbearing age with breast cancer, to reduce reproductive concerns.

miRNA-874-3p inhibits the migration, invasion and proliferation of breast cancer cells by targeting VDAC1.

Breast cancer is an important cause of crisis for womens life and health. Voltage-dependent anion channel 1 (VDAC1) is mainly localized in the outer mitochondrial membrane of all eukaryotes, and it plays a crucial role in the cell as the main interface between mitochondria and cellular metabolism. Through bioinformatics, we found that VDAC1 is abnormally highly expressed in breast cancer, and the prognosis of breast cancer patients with high VDAC1 expression is poor. Through

ECM-targeting bacteria enhance chemotherapeutic drug efficacy by lowering IFP in tumor mouse models.

Bacterial cancer therapies aim to manipulate bacteria to effectively deploy therapeutic payloads to tumors. Attenuated bacteria alone often cannot eradicate solid tumors. Attenuated Salmonella can be engineered to deliver cytotoxic drugs to either trigger an immune response or increase antitumor efficacy when combined with chemotherapeutic drugs. However, the extracellular matrix (ECM) surrounding cancer cells forms a barrier that often limits the ability of chemotherapeutic and cytotoxic drugs to penetrate and eliminate tumors. To overcome this limitation, we developed a strategy to combine chemotherapy with an attenuated Salmonella typhimurium strain engineered to secrete HysA protein (from Staphylococcus aureus Hyaluronidase, HAase) in tumors. The engineered Salmonella effectively degraded hyaluronan (HA), which is a major ECM constituent in tumors, and suppressed tumor growth in mouse models of pancreatic adenocarcinoma (ASPC-1) and breast cancer (4T1). Furthermore, it prolonged survival when combined with chemotherapeutic drugs (doxorubicin or gemcitabine). Upon bacterial colonization, the HAase-mediated ECM degradation decreased interstitial fluid pressure (IFP) in the tumor microenvironment. Additionally, HA degradation using HAase-expressing bacteria in vivo led to decreased binding to the receptor, CD44, expressed in tumors. This may modulate proliferation- and apoptosis-related signal pathways. Therefore, ECM-targeting bacteria can be used as a synergistic anticancer therapeutic agent to maximize chemotherapeutic drug delivery into highly invasive tumors.

Associations of body fat mass and fat-free mass with breast cancer incidence in postmenopausal women A Danish prospective cohort study.

Previous studies have established associations between body mass index (BMI) and breast cancer, but fat mass is a more direct measure of the amount of fat tissue in the body than BMI. This study examined the association between body fat mass (BFM), fat-free mass (FFM) and other anthropometric measures and breast cancer in postmenopausal women according to use of hormone replacement therapy (HRT). From the Danish Diet, Cancer and Health cohort established during 1993-1997, 24,219 postmenopausal women were included who had anthropometric and bioimpedance measurements performed by a laboratory technician at baseline. Information on breast cancer incidence (outcome), other cancer diagnoses and vital status (censoring variables) through 2016 was obtained from nationwide registers. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) while adjusting for known breast cancer risk factors and stratifying by HRT use and running age. During a total of 431,104 person-years, 1,919 women developed breast cancer. Among never users of HRT, the HR for breast cancer at or after age 65 years was 1.06 (95 % CI 1.03-1.08) per 1 kgm Among postmenopausal women who never used HRT, BFMI was associated with breast cancer in women older than 65 years. FFMI was found to be more strongly associated with postmenopausal breast cancer incidence than BFMI independently of age in never users of HRT.

Circulating glypican-4 is a predictor of 24-month overall survival in metastatic breast cancer.

Endocrine treatment combined with CDK46 inhibitors is the preferred treatment strategy in patients presenting with ER-positiveHER2-negative breast cancer, but the clinical course remains highly variable among individual patients. There is an unmet need for prognostic or predictive biomarkers in this important group of patients. Recently, we have identified circulating glypican-4 (GPC4) as a new biomarker of inferior outcomes in patients with metastatic colorectal cancer. The impact of plasma GPC4 levels on the survival of breast cancer patients is unknown and has been addressed in the present study. Our study included 47 patients with ER-positiveHER2-negative metastatic breast cancer prior to treatment with CDK46 inhibitors combined with endocrine therapy. The endpoint was overall survival (OS) at 24 months. GPC4 levels were measured in plasma using an enzyme-linked immunosorbent assay. Increased circulating GPC4 levels were significantly linked to advanced age, postmenopausal state, visceral metastases, and invasive lobular carcinoma. During the two-year observational follow-up period, 25.5 % of patients died. The area under the receiver operating characteristic curve (ROC-AUC) analysis revealed an AUC of 0.713 0.555-0.871 P0.029 for OS and an optimal cut-off value of GPC4 for predicting OS of 4.77 ngmL. No patient showing GPC4 values below this cut-off died during the observational period. Cox regression analysis showed a hazard ratio of 2.14 95% confidence interval 1.24-3.67 P0.006 for one standard deviation change of plasma GPC4. In conclusion, our study suggests circulating GPC4 as a significant predictor of poor survival in metastatic breast cancer patients.

Discovery of 2-(3-Benzamidopropanamido)thiazole-5-carboxylate Inhibitors of the Kinesin HSET (KIFC1) and the Development of Cellular Target Engagement Probes.

The existence of multiple centrosomes in some cancer cells can lead to cell death through the formation of multipolar mitotic spindles and consequent aberrant cell division. Many cancer cells rely on HSET (KIFC1) to cluster the extra centrosomes into two groups to mimic the bipolar spindle formation of non-centrosome-amplified cells and ensure their survival. Here, we report the discovery of a novel 2-(3-benzamidopropanamido)thiazole-5-carboxylate with micromolar in vitro inhibition of HSET (KIFC1) through high-throughput screening and its progression to ATP-competitive compounds with nanomolar biochemical potency and high selectivity against the opposing mitotic kinesin Eg5. Induction of the multipolar phenotype was shown in centrosome-amplified human cancer cells treated with these inhibitors. In addition, a suitable linker position was identified to allow the synthesis of both fluorescent- and

Novel Algorithm for the Estimation of Cancer Incidence Using Claims Data in Japan A Feasibility Study.

We developed algorithms to identify patients with newly diagnosed cancer from a Japanese claims database to identify the patients with newly diagnosed cancer of the sample population, which were compared with the nationwide cancer incidence in Japan to assess the validity of the novel algorithms. We developed two algorithms to identify patients with stomach, lung, colorectal, breast, and cervical cancers diagnosis only (algorithm 1), and combining diagnosis, treatments, and medicines (algorithm 2). Patients with newly diagnosed cancer were identified from an anonymized commercial claims database (JMDC Claims Database) in 2017 with two inclusionsexclusion criteria selecting all patients with cancer (extract 1) and excluding patients who had received cancer treatments in 2015 or 2016 (extract 2). We estimated the cancer incidence of the five cancer sites and compared it with the Japan National Cancer Registry incidence (calculated standardized incidence ratio with 95% CIs). The number of patients with newly diagnosed cancer ranged from 219 to 17,840 by the sites, algorithms, and exclusion criteria. Standardized incidence ratios were significantly higher in the JMDC Claims Database than in the national registry data for extract 1 and algorithm 1, extract 1 and algorithm 2, and extract 2 and algorithm 1. In extract 2 and algorithm 2, colorectal cancer in male and stomach, lung, and cervical cancers in females showed similar cancer incidence in the JMDC and national registry data. The novel algorithms are effective for extracting information about patients with cancer from claims data by using the combined information on diagnosis, procedures, and medicines (algorithm 2), with 2-year cancer-treatment history as an exclusion criterion (extract 2).

CCNE1 and PLK1 mediates resistance to palbociclib in HRHER2- metastatic breast cancer.

In HRHER2- metastatic breast cancer (MBC) is imperative to identify patients who respond poorly to CDK46i and to discover therapeutic targets to reverse this resistance. Non-luminal breast cancer subtype and high levels of CCNE1 are candidate biomarkers in this setting but further validation is needed. We performed mRNA gene expression profiling and correlation with progression-free-survival (PFS) on 455 tumor samples included in the phase III PEARL study, that assigned HRHER2- MBC patients to receive palbociclibET vs capecitabine. ERHER2- breast cancer cell lines were used to generate and characterize resistance to palbociclibET. Non-luminal subtype was more prevalent in metastatic (14%) than in primary tumor samples (4%). Patients with non-luminal tumors had median PFS of 2.4months (m) with palbociclibET and 9.3m with capecitabine HR4.16, adjusted p-value<0.0001. Tumors with high CCNE1 expression (above median) had also worse median PFS with palbociclibET (6.2m) than with capecitabine (9.3m) HR1.55, adjusted p-value0.0036. In patients refractory to palbociclibET (PFS in the lower quartile) we found higher levels of Polo Like Kinase 1 (PLK1). In an independent data set (PALOMA3), tumors with high PLK1 show worse median PFS than those with low PLK1 expression under palbociclibET treatment. In ERHER2- cell line models we show that PLK1 inhibition reverses resistance to palbociclibET. We confirm the association of non-luminal subtype and CCNE1 with resistance to CDK46iET in HR MBC. High levels of PLK1 mRNA identify patients with poor response to palbociclib, suggesting PLK1 could also play a role in the setting of resistance to CDK46i.

Patients Individualized Care Perceptions and Health Literacy Using an Interactive App During Breast and Prostate Cancer Treatment Two Parallel Randomized Controlled Trials.

The use of symptom management mobile apps can reduce patients symptom burden during cancer treatment, but the evidence is lacking about their effect on care. Moreover, if patients health literacy can be improved, it needs to be more rigorously tested. This study aimed to evaluate patients perceptions of individualized care and health literacy using an interactive app in two randomized trials. Patients undergoing neoadjuvant chemotherapy for breast cancer (N 149) and radiotherapy for prostate cancer (N 150) were consecutively included and randomized into one intervention or control group. Outcome measures were Individualized Care Scale, Swedish Functional Health Literacy Scale, and Swedish Communicative and Critical Health Literacy Scale. In the breast cancer trial, no group differences were observed regarding individualized care or health literacy. Most patients had sufficient health literacy levels. In the prostate cancer trial, intervention group patients rated higher perceived individualized care regarding decision control at follow-up than the control group. Less than half had sufficient health literacy levels and intervention group patients significantly improved their ability to seek, understand, and communicate health information. Education level explained significant variance in health literacy in both trials. Using an interactive app can positively affect individualization in care and health literacy skills among patients treated for prostate cancer, although further research is warranted.

The ubiquitin ligase TRIM21 regulates mutant p53 accumulation and gain-of-function in cancer.

Tumor suppressor TP53 is the most frequently mutated gene in human cancers. Mutant p53 (mutp53) proteins often accumulate to very high levels in human cancers to promote cancer progression through the gain-of-function (GOF) mechanism. Currently, the mechanism underlying mutp53 accumulation and GOF is incompletely understood. Here, we identified TRIM21 as a critical E3 ubiquitin ligase of mutp53 by screening for specific mutp53-interacting proteins. TRIM21 directly interacted with mutp53 but not wild-type p53, resulting in ubiquitination and degradation of mutp53 to suppress mutp53 GOF in tumorigenesis. TRIM21 deficiency in cancer cells promoted mutp53 accumulation and GOF in tumorigenesis. Compared with p53R172H knock-in mice, which displayed mutp53 accumulation specifically in tumors but not normal tissues, TRIM21 deletion in p53R172H knock-in mice resulted in mutp53 accumulation in normal tissues, an earlier tumor onset, and a shortened lifespan of mice. Furthermore, TRIM21 was frequently downregulated in some human cancers, including colorectal and breast cancers, and low TRIM21 expression was associated with poor prognosis in patients with cancers carrying mutp53. Our results revealed a critical mechanism underlying mutp53 accumulation in cancers, and also uncovered an important tumor-suppressive function of TRIM21 and its mechanism in cancers carrying mutp53.

Breast Cancer Screening, Diagnosis, and Surgery during the Pre- and Peri-pandemic Experience of Patients in a Statewide Health Information Exchange.

Measures taken to address the COVID-19 pandemic interrupted routine diagnosis and care for breast cancer. The aim of this study was to characterize the effects of the pandemic on breast cancer care in a statewide cohort. Using data from a large health information exchange, we retrospectively analyzed the timing of breast cancer screening, and identified a cohort of newly diagnosed patients with any stage of breast cancer to further access the information available about their surgical treatments. We compared data for four subgroups pre-lockdown (preLD) 25 March to 16 June 2019 lockdown (LD) 23 March to 3 May 2020 reopening (RO) 4 May to 14 June 2020 and post-lockdown (postLD) 22 March to 13 June 2021. During LD and RO, screening mammograms in the cohort decreased by 96.3% and 36.2%, respectively. The overall breast cancer diagnosis and surgery volumes decreased up to 38.7%, and the median time to surgery was prolonged from 1.5 months to 2.4 for LD and 1.8 months for RO. Interestingly, higher mean DCIS diagnosis (5.0 per week vs. 3.1 per week, p < 0.05) and surgery volume (14.8 vs. 10.5, p < 0.05) were found for postLD compared with preLD, while median time to surgery was shorter (1.2 months vs. 1.5 months, p < 0.0001). However, the postLD average weekly screening and diagnostic mammogram did not fully recover to preLD levels (2055.3 vs. 2326.2, p < 0.05 574.2 vs. 624.1, p < 0.05). Breast cancer diagnosis and treatment patterns were interrupted during the lockdown and still altered 1 year after. Screening in primary care should be expanded to mitigate possible longer-term effects of these interruptions.

Breast MRI Clinical Indications, Recommendations, and Future Applications in Breast Cancer Diagnosis.

This article aims to provide an updated overview of the indications for diagnostic breast magnetic resonance imaging (MRI), discusses the available and novel imaging exams proposed for breast cancer detection, and discusses considerations when performing breast MRI in the clinical setting. Breast MRI is superior in identifying lesions in women with a very high risk of breast cancer or average risk with dense breasts. Moreover, the application of breast MRI has benefits in numerous other clinical cases as well e.g., the assessment of the extent of disease, evaluation of response to neoadjuvant therapy (NAT), evaluation of lymph nodes and primary occult tumor, evaluation of lesions suspicious of Pagets disease, and suspicious discharge and breast implants. Breast cancer is the most frequently detected tumor among women around the globe and is often diagnosed as a result of abnormal findings on mammography. Although effective multimodal therapies significantly decline mortality rates, breast cancer remains one of the leading causes of cancer death. A proactive approach to identifying suspicious breast lesions at early stages can enhance the efficacy of anti-cancer treatments, improve patient recovery, and significantly improve long-term survival. However, the currently applied mammography to detect breast cancer has its limitations. High false-positive and false-negative rates are observed in women with dense breasts. Since approximately half of the screening population comprises women with dense breasts, mammography is often incorrectly used. The application of breast MRI should significantly impact the correct cases of breast abnormality detection in women. Radiomics provides valuable data obtained from breast MRI, further improving breast cancer diagnosis. Introducing these constantly evolving algorithms in clinical practice will lead to the right breast detection tool, optimized surveillance program, and individualized breast cancer treatment.

Validation of a breast cancer risk prediction model based on the key risk factors family history, mammographic density and polygenic risk.

We compared a simple breast cancer risk prediction model, BRISK (which includes mammographic density, polygenic risk and clinical factors), against a similar model with more risk factors (simplified Rosner) and against two commonly used clinical models (Gail and IBIS). Using nested case-control data from the Nurses Health Study, we compared the models association, discrimination and calibration. Classification performance was compared between Gail and BRISK for 5-year risks and between IBIS and BRISK for remaining lifetime risk. The odds ratio per standard deviation was 1.43 (95% CI 1.32, 1.55) for BRISK 5-year risk, 1.07 (95% CI 0.99, 1.14) for Gail 5-year risk, 1.72 (95% CI 1.59, 1.87) for simplified Rosner 10-year risk, 1.51 (95% CI 1.41, 1.62) for BRISK remaining lifetime risk and 1.26 (95% CI 1.16, 1.36) for IBIS remaining lifetime risk. The area under the receiver operating characteristic curve (AUC) was improved for BRISK over Gail for 5-year risk (AUC 0.636 versus 0.511, P < 0.0001) and for BRISK over IBIS for remaining lifetime risk (AUC 0.647 versus 0.571, P < 0.0001). BRISK was well calibrated for the estimation of both 5-year risk (expectedobserved EO 1.03 95% CI 0.73, 1.46) and remaining lifetime risk (EO 1.01 95% CI 0.86, 1.17). The Gail 5-year risk (EO 0.85 95% CI 0.58, 1.24) and IBIS remaining lifetime risk (EO 0.73 95% CI 0.60, 0.87) were not well calibrated, with both under-estimating risk. BRISK improves classification of risk compared to Gail 5-year risk (NRI 0.31 standard error SE 0.031) and IBIS remaining lifetime risk (NRI 0.287 SE 0.035). BRISK performs better than two commonly used clinical risk models and no worse compared to a similar model with more risk factors.

Variability Among Breast Cancer Risk Classification Models When Applied at the Level of the Individual Woman.

Breast cancer risk models guide screening and chemoprevention decisions, but the extent and effect of variability among models, particularly at the individual level, is uncertain. To quantify the accuracy and disagreement between commonly used risk models in categorizing individual women as average vs. high risk for developing invasive breast cancer. Comparison of three risk prediction models Breast Cancer Risk Assessment Tool (BCRAT), Breast Cancer Surveillance Consortium (BCSC) model, and International Breast Intervention Study (IBIS) model. Women 40 to 74 years of age presenting for screening mammography at a multisite health system between 2011 and 2015, with 5-year follow-up for cancer outcome. Comparison of model discrimination and calibration at the population level and inter-model agreement for 5-year breast cancer risk at the individual level using two cutoffs (≥ 1.67% and ≥ 3.0%). A total of 31,115 women were included. When using the ≥ 1.67% threshold, more than 21% of women were classified as high risk for developing breast cancer in the next 5 years by one model, but average risk by another model. When using the ≥ 3.0% threshold, more than 5% of women had disagreements in risk severity between models. Almost half of the women (46.6%) were classified as high risk by at least one of the three models (e.g., if all three models were applied) for the threshold of ≥ 1.67%, and 11.1% were classified as high risk for ≥ 3.0%. All three models had similar accuracy at the population level. Breast cancer risk estimates for individual women vary substantially, depending on which risk assessment model is used. The choice of cutoff used to define high risk can lead to adverse effects for screening, preventive care, and quality of life for misidentified individuals. Clinicians need to be aware of the high false-positive and false-negative rates and variation between models when talking with patients.

Vitamin D metabolism in cancer potential feasibility of vitamin D metabolism blocking therapy.

In this review, we discuss the possibility of the vitamin D metabolizing enzyme CYP24A1 being a therapeutic target for various tumors including breast, colorectal and prostate tumors. Given the pleiotropic cellular activity of vitamin D, its deficiency impairs its physiological function in target cells and results in various pathologies including cancer. In addition, accumulated data have shown that elevated expression of CYP24A1 promotes carcinogenesis in various cancer subtypes by decreasing the bioavailability of vitamin D metabolites. Thus, we propose the potential feasibility of vitamin D metabolism-blocking therapy in various types of human malignancies that express constitutive CYP24A1.

Association between periodontitis and breast cancer two-sample Mendelian randomization study.

The purpose of this study was to investigate whether there is a causal relationship between periodontitis and breast cancer by Mendelian randomization analysis. We performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied complementary methods, including weighted median, weighted mode, simple mode, MR-Egger regression, and MR-pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy. IVW MR analysis showed no effect of periodontitis on breast cancer (IVW OR0.99, P 0.14). Similarly, no significant causal relationship between breast cancer and periodontitis was found in reverse MR analysis (IVW OR0.95, P 0.83). The results of MR-Egger regression, weighted median, and weighted mode methods were consistent with those of the IVW method. Based on sensitivity analyses, horizontal pleiotropy is unlikely to distort causal estimates. Although observational studies have reported an association between periodontitis and breast cancer, the results of our MR analysis do not support a causal relationship between periodontitis and breast cancer. Mendelian randomization study can more clearly analyze the causal relationship between periodontitis and breast cancer, in order to provide a certain reference for clinicians and deepen the understanding of the relationship between periodontitis and breast cancer, to explore more possible associations between periodontitis and systemic diseases.

Bifunctional photoelectrochemical aptasensor based on heterostructured Ag

Constructing of heterostructures can significantly improve the photoelectrical (PEC) response signal by promoting the migration and suppressing the recombination of photogenerated carries. A bifunctional PEC sensing platform was designed for simultaneous high-performance detection of mucin-1 (MUC1) and carcinoembryonic antigen (CEA), which was based on generated Z-scheme heterostructured Ag

Management of Menopausal Symptoms A Review.

Menopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years. During the menopausal transition, approximately 50% to 75% of women have hot flashes, night sweats, or both (vasomotor symptoms) and more than 50% have genitourinary symptoms (genitourinary syndrome of menopause GSM). Vasomotor symptoms typically last more than 7 years and GSM is often chronic. Efficacious treatments for women with bothersome vasomotor symptoms or GSM symptoms include hormonal and nonhormonal options. Systemic estrogen alone or combined with a progestogen reduces the frequency of vasomotor symptoms by approximately 75%. Oral and transdermal estrogen have similar efficacy. Conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA) were the only hormonal treatments for which clinical trials were designed to examine cardiovascular events, venous thromboembolism, and breast cancer risk. Compared with placebo, the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) and breast cancer (with use of CEE plus MPA) is approximately 1 excess event1000 person-years. Low-dose CEE plus bazedoxifene is not associated with increased risk of breast cancer (0.25%year vs 0.23%year with placebo). Bioidentical estrogens approved by the US Food and Drug Administration (with identical chemical structure to naturally produced estrogens, and often administered transdermally) also are available to treat vasomotor symptoms. For women who are not candidates for hormonal treatments, nonhormonal approaches such as citalopram, desvenlafaxine, escitalopram, gabapentin, paroxetine, and venlafaxine are available and are associated with a reduction in frequency of vasomotor symptoms by approximately 40% to 65%. Low-dose vaginal estrogen is associated with subjective improvement in GSM symptom severity by approximately 60% to 80%, with improvement in severity by 40% to 80% for vaginal prasterone, and with improvement in severity by 30% to 50% for oral ospemifene. During the menopausal transition, approximately 50% to 75% of women have vasomotor symptoms and GSM symptoms. Hormonal therapy with estrogen is the first-line therapy for bothersome vasomotor symptoms and GSM symptoms, but nonhormonal medications (such as paroxetine and venlafaxine) also can be effective. Hormone therapy is not indicated for the prevention of cardiovascular disease.

The Impact of the Pathologist in Multidisciplinary Cancer Conferences on Patient Care.

Multidisciplinary cancer conferences (MCCs) are important tools in the treatment of patients with complex health issues, helping clinicians achieve optimal outcomes in oncological practice. To explore the role of pathologists at MCCs, we conducted a review of prior research on this topic. We conducted a scoping review by searching MEDLINE, EMBASE, and the Cochrane Library for English-language qualitative, quantitative, or multiplemixed methods studies on the role and impact of pathologists on MCCs. We used Microsoft Excel to extract data. Of 76 research results, we included only 3 studies that involved review of cancer cases by pathologists for MCCs. All 3 studies showed that expert pathology review improved the accuracy of diagnosis and refined disease staging, leading to changes in the management of melanoma, breast cancer, and gynecologic cancer. No studies explored the barriers to pathologists participating in MCCs or the strategies or interventions employed to promote or support pathologist involvement. We identified a paucity of studies on the role of pathologists in MCCs. Given the positive impact of MCCs involving pathologists on the accuracy of diagnosis and optimization of treatment, future research is warranted to further establish the role and impact of pathologists in MCCs and how to promote or support pathologists involvement.

The extreme phenotype approach applied to male breast cancer allows the identification of rare variants of ATR as potential breast cancer susceptibility alleles.

In oncogenetics, some patients could be considered as extreme phenotypes, such as those with very early onset presentation or multiple primary malignancies, unusually high numbers of cancers of the same spectrum or rare cancer types in the same parental branch. For these cases, a genetic predisposition is very likely, but classical candidate gene panel analyses often and frustratingly remains negative. In the framework of the EX

Beyond Breast Density Risk Measures for Breast Cancer in Multiple Imaging Modalities.

Breast density is an independent risk factor for breast cancer. In digital mammography and digital breast tomosynthesis, breast density is assessed visually using the four-category scale developed by the American College of Radiology Breast Imaging Reporting and Data System (5th edition as of November 2022). Epidemiologically based risk models, such as the Tyrer-Cuzick model (version 8), demonstrate superior modeling performance when mammographic density is incorporated. Beyond just density, a separate mammographic measure of breast cancer risk is parenchymal textural complexity. With advancements in radiomics and deep learning, mammographic textural patterns can be assessed quantitatively and incorporated into risk models. Other supplemental screening modalities, such as breast US and MRI, offer independent risk measures complementary to those derived from mammography. Breast US allows the two components of fibroglandular tissue (stromal and glandular) to be visualized separately in a manner that is not possible with mammography. A higher glandular component at screening breast US is associated with higher risk. With MRI, a higher background parenchymal enhancement of the fibroglandular tissue has also emerged as an imaging marker for risk assessment. Imaging markers observed at mammography, US, and MRI are powerful tools in refining breast cancer risk prediction, beyond mammographic density alone.

Resolution of Nonmass Enhancement Extension to the Nipple at Breast MRI after Neoadjuvant Chemotherapy Pathologic Response and Feasibility for Nipple-sparing Mastectomy.

Background Nipple-sparing mastectomy (NSM) is usually contraindicated in patients with nonmass enhancement (NME) extension to the nipple at breast MRI. However, little is known about the feasibility of NSM when NME extension to the nipple resolves after neoadjuvant chemotherapy (NAC). Purpose To evaluate whether NSM is an appropriate surgical procedure for patients in whom NME extension to the nipple resolves after NAC. Materials and Methods This retrospective study included 383 women with NME at baseline MRI who underwent NAC followed by mastectomy between January 2007 and March 2022 at a single institution. NME extension to the nipple was assessed using breast MRI before NAC (hereafter, pre-NAC) and after NAC (hereafter, post-NAC). In 326 women who underwent mastectomy with removal of the nipple-areolar complex, the rate of pathologic analysis-confirmed tumor invasion of the nipple compared with NME extension to the nipple at post-NAC breast MRI was evaluated. Tumor involvement of the nipple was also assessed in those with complete pathologic response at posttreatment MRI. Furthermore, the outcomes in 57 women undergoing NSM were investigated, particularly in patients with NME extension to the nipple at initial diagnosis. Results Of the 326 women who underwent mastectomy with removal of the nipple-areolar complex (mean age, 49 years ± 9.4 SD), 217 patients (67%) showed NME extension to the nipple on pre-NAC MRI scans. Among the 153 women (70%) in whom the NME extension to the nipple resolved after NAC, the rate of pathologic analysis-confirmed tumor invasion of the nipple was 2.6% (four of 153 women 95% CI 0, 6.5). No pathologic analysis-confirmed tumor invasion of the nipple was detected in 31 women with complete response at MRI. Of the 57 women who underwent NSM, 12 (21%) with resolution of NME extension to the nipple after NAC had no relapse during the median follow-up of 31 months (range, 11-80 months). Conclusion Pathologic analysis-confirmed tumor invasion of the nipple was rare in women with resolution of nonmass enhancement extension to the nipple after neoadjuvant chemotherapy (NAC). Therefore, nipple-sparing mastectomy could be feasible in this population, especially in those with complete MRI response to NAC. © RSNA, 2023

Antimicrobial, Antioxidant, Cytotoxicity and DNA Protective Properties of the Pink Oyster Mushroom, Pleurotus djamor (Agaricomycetes).

In this study, pink oyster mushroom Pleurotus djamor was cultivated using wheat straw (WS), quinoa stalk (QS), and their mixtures (WS-QS (11)) as substrate and evaluated in terms of antimicrobial, antioxidant, cytotoxicity, and DNA protective effects. Gram-positive and Gram-negative pathogen bacteria (Bacillus subtilis, Proteus vulgaris, Streptococcus mutans, Salmonella typhi, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli), dermatophyte (Trichophyton sp.) and yeast (Candida tropicalis) were used in the study. It was found to be very active against all bacteria (except S. mutans and S. typhi), and dermatophyte when compared to the control groups (8.7-33.3 mm), but low against C. tropicalis. It was seen that the best total antioxidant assay (TAS) value was 2.05 mmolL on WS-QS (11). Depend on, it was determined that the total oxidant assay (TOS) value (5.26 μmolL) in the same compost was lower than the others, and also the scavenging effect of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) was higher on WS at 25 mgmL (84.20%). The methanol extract on WS at a concentration of 400 μgmL, significantly reduced the percentage of viability in the human breast cancer (MDA-MB-231) cell line (2.2%). The methanol extracts on WS and QS medium were found to inhibit DNA damage induced by UV radiation and H2O2 at a concentration of 25 mgmL. These results showed that pink oyster mushroom has benefits such as antimicrobial, antioxidant, cytotoxic, and DNA protective effects.

Long COVID in cancer patients preponderance of symptoms in majority of patients over long time period.

Research Progress on Gene Synthesis and Anticancer and Lipid-lowering Mechanism of Monacolin K.

Monacolin K (MK), also known as lovastatin (LOV), is a secondary metabolite synthesized by Monascus in the later stage of fermentation and is the main component of functional red yeast rice (RYR). The structure of MK is similar to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), and it can competitively bind to 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), thus reducing the level of blood lipids. MK can affect the expression of MAPK, PI3KAKT, and NF-κB pathway, prepare conjugates with other compounds, and enhance the sensitivity of cancer cells to chemotherapeutic drugs so as to induce apoptosis of acute myeloid leukemia, prostate cancer, breast cancer, lung cancer, gastric cancer, and liver cancer. Combined with the synthetic route of MK, this paper summarizes the latest lipid-lowering and anticancer mechanism of MK, and provides a reference for the application of MK in medicine.

Cytological study of 44 cases with solid papillary carcinoma and a systemic review of solid papillary carcinoma and neuroendocrine tumor of the breast.

Solid-papillary carcinoma (SPC) of the breast is a rare variant of low-grade in situ and invasive carcinoma but there are only a few of the cytologic studies. We examined 44 cases of SPC of the breast to define the cytologic features. We also made a systemic review of reported cases of SPC and neuroendocrine tumor (NET) of the breast. Both of our and the reviewed cases with SPC were very similar in the cytologic finding. It included hypercellularity, highly discohesive clusters, numerous isolated cells, small nuclei, finely granular chromatin of salt-and-pepper appearance, inconspicuous nucleoli, low nuclear-cytoplasmic ratio, and a plasmacytoid appearance. Moreover, SPC and NET had frequently all of these features in common. Capillary vessels structures and mucinous substance were not frequently seen in our and the reviewed cases with SPC. Rosette and pseudorosette were very rare in the cytologic specimen. The immunocytochemistry with our 9 cases with SPC indicated diffuse positivity for chromogranin A andor synaptophysin. Many cytologic features are frequently shared by SPC and NET of the breast. However, the vascular structure may not be a precise criterion for SPC. Rosette and pseudorosette are rarely helpful for the cytologic diagnosis.

Do young adults with cancer receive information about treatment-related impact on sex life Results from a population-based study.

Sexual dysfunction is common following a cancer diagnosis in young adulthood (18-39 years) and problems related to sex life are ranked among the core concerns in this age group. Yet, few studies have investigated to what extent adults younger than 40, receive information from healthcare providers about the potential impact of cancer and its treatment on their sex life. A population-based cross-sectional survey study was conducted with 1010 young adults 1.5 years after being diagnosed with cancer (response rate 67%). Patients with breast, cervical, ovarian and testicular cancer, lymphoma, and brain tumors were identified in national quality registries. Sociodemographic and clinical factors associated with receiving information were examined using multivariable binary logistic regression. Men to a higher extent than women reported having received information about potential cancer-related impact on their sex life (68% vs. 54%, p < 0.001). Receipt of information varied across diagnoses in separate regression models, using lymphoma as reference, both women and men with brain tumors were less likely to receive information (women OR 0.10, CI 0.03-0.30 men OR 0.37, CI 0.16-0.85). More intensive treatment was associated with higher odds of receiving information in both women (OR 1.89 CI 1.28-2.79) and men (OR 2.08 CI 1.09-3.94). None of the sociodemographic factors were associated with receipt of information. To improve sexual health communication to young adults with cancer, we recommend diagnosis-specific routines that clarify when in the disease trajectory to discuss these issues with patients and what to address in these conversations.

Measuring high-risk parents opinions about direct-to-consumer genetic testing for adult-onset inherited cancer syndromes in their adolescent and young adult children.

Neither direct-to-consumer (DTC) genetic testing nor predictive genetic testing for adult-onset conditions is recommended for minor children due to ethical concerns and low clinical utility. However, parents with pathogenic variants (PVs) in disease-causing genes may be interested in pursuing genetic testing that includes the familial PV for their children. The Pediatric Testing Attitudes Scale (P-TAS) was previously developed to examine high-risk parents opinions about pediatric BRCA genetic testing for adult-onset breastovarian cancer. Here, the psychometric properties of the P-TAS were examined in a new sample of N 126 parents (M age 47.2 years) with PVs in a more complete set of cancer risk genes represented on DTC panel tests. The mean score on the P-TAS was 44 out of a maximum score of 60, indicating that a majority of parents generally held favorable opinions about testing their children for adult-onset inherited cancer syndromes. The internal consistency of the full scale was high (α 0.91). A factor analysis identified two-component scales, labeled Attitudes and Beliefs (α 0.93) and Decision Making and Communication (α 0.83). In a multivariable regression model, P-TAS co-factors accounted for 34% of variance in parental opinions, including the frequency of prior family communication about cancer and the likelihood of utilizing DTC genetic testing with children (R

Involvement of protumor macrophages in breast cancer progression and characterization of macrophage phenotypes.

Tumor-associated macrophages (TAMs) are the most prominent immune cells in the breast cancer microenvironment, and the protumor functions of TAMs are thought to affect cancer progression and resistance to anti-cancer therapy. Numerous studies using human breast cancer samples, cell lines, and murine breast cancer models have revealed details of the mechanisms by which the protumor functions of TAMs are activated. Recent advances have highlighted the significant involvement of TAMs in the resistance of breast cancer cells to immunotherapy. TAMs express a number of immunosuppressive genes, and single-cell sequence analyses of human and murine cancer samples have helped elucidate the mechanism of TAM-induced immunosuppression. As TAMs are considered suitable targets for anti-cancer therapies, we summarized the protumor functions of TAMs and the potential of anti-cancer therapies targeting TAMs, with a focus on breast cancer research.

Is Magnetic Resonance Imaging (MRI) still a Gold Standard to Detect Breast Cancer A Meta-analysis.

Breast cancer is fatal if it is not diagnosed and treated promptly consequently, early and precise diagnosis is essential. In comparison to mammography and sonography, the sensitivity of MRI to cellular changes and its ability to differentiate benign from malignant tumors make it the preferred imaging technique. Consequently, the present meta-analysis assessed the effectiveness of different imaging modalities for breast cancer detection and evaluated the diagnostic accuracy of MRI. Pertinent articles were searched in PubMed, MEDLINE, and Central databases using the appropriate keywords as per the PRISMA guidelines. Retrospective and prospective studies were included according to the predefined PICOS criteria. A meta-analysis was performed using RevMan and MedCalc software, and statistical parameters, such as odds ratio, sensitivity, specificity, likelihood ratios, and accuracy, were calculated. Publication bias was evaluated using Eggers and Beggs tests, and diagnostic performance was assessed using Youdens and Bland-Altmans plots. Fourteen clinical trials with 4666 breast cancer patients with perineural spread were included. The included studies used MRI for the detection of breast cancer lesions according to the BI-RADS® (Breast Imaging Reporting and Data System) guidelines and stated that it has high sensitivity and diagnostic accuracy. Similarly, the present meta-analysis found a high sensitivity of 86.12 % and a high diagnostic accuracy of 91.2%. Other than this, we obtained a specificity of 65%, a positive likelihood ratio of 2.7, and a negative likelihood ratio of 0.22. The pooled odds ratio (OR) was reported to be 1.87 (95% CI 1.42-2.46), and the pooled risk ratio value was 1.19 (95% CI 1.11-1.28). Present meta-analysis strongly recommends MRI as an effective imaging method for the detection of breast cancer.

Risk-Adapted Target Delineation for Breast Cancer Controversies and Considerations.

The advent of computed tomography-based planning coupled with modern tools for target delineation and hypofractionated treatment schedules has increased efficiency and throughput for patients with breast cancer. While the benefit of adjuvant radiation therapy (RT) in reducing locoregional recurrences is established, disentangling local versus regional recurrence risks with modern treatment protocols has become an area of active research to de-escalate treatment. Delineation guidelines for nodal regions either attempt to replicate results of conventional RT techniques by translating bony landmarks to clinical target volumes or use landmarks based on the fact that lymphatic channels run along the vasculature. Because direct comparisons of both approaches are implausible, mapping studies of nodal recurrences have reported on the proportion of nodes included in these delineation guidelines, and larger, bony, landmark-based guidelines appear intuitively appealing for patients with unfavorable risk factors. A pooled analysis of these studies is reported here, along with literature supporting the exclusion of the true chest wall from postmastectomybreast-conserving surgery clinical target volumes and the selective (versus routine) use of bolus during postmastectomy RT. The risk-adapted approach suggested here accounts for the risk of recurrence as well as toxicity and endorses nuanced target volume delineation rather than a one-size-fits-all approach.

Transformation of breast micropapillary ductal carcinoma in situ into invasive micropapillary carcinoma after recurrence in chest wall report of a case.

乳腺导管内癌是一种常见的乳腺原位癌，因肿瘤未突破基底膜，手术切除通常有效，少部分复发，极少部分以浸润癌复发。本文报道1例微乳头型乳腺导管内癌，乳腺改良根治术和内分泌治疗4年后出现同侧胸壁浸润性微乳头状癌复发，再次行化疗放疗内分泌治疗后随访3年无异常。本文回顾其临床病理资料并复习相关文献，以提高对该病的认识，并探讨可能的治疗方案。.

Pathological features and clinicopathological significance of TERT promoter mutation in breast fibroepithelial tumors without definite diagnosis.

Rational approaches to discover SARS-CoV-2ACE2 interaction inhibitors Pharmacophore-based virtual screening, molecular docking, molecular dynamics and binding free energy studies.

The lack of effective treatment remains a bottleneck in combating the current coronavirus family pandemic, particularly coronavirus 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection of host cells by SARS-CoV-2 is mediated by the binding of its receptor-binding domain (RBD) on the spike (S) glycoprotein to the host angiotensin-converting enzyme (ACE2) receptor. As all developed and available vaccines against COVID-19 do not provide long-term immunity, the creation of an effective drug for the treatment of COVID-19 is necessary and cannot be ignored. Therefore, the aim of this study is to present a computational screening method to identify potential inhibitor candidates with a high probability of blocking the binding of RBD to the ACE2 receptor. Pharmacophore mapping, molecular docking, molecular dynamics (MD) simulations, and binding free-energy analyses were performed to identify potential inhibitor candidates against ACE2SARS-CoV-2. In conclusion, we propose the compound PubChem-84280085 as a potential inhibitor of protein-protein interactions to disrupt the binding of the SARS-CoV-2-RBD to the ACE2 receptor.

CTC-5 A novel digital pathology approach to characterise circulating tumour cell biodiversity.

Metastatic progression and tumor evolution complicates the clinical management of cancer patients. Circulating tumor cell (CTC) characterization is a growing discipline that aims to elucidate tumor metastasis and evolution processes. CTCs offer the clinical potential to monitor cancer patients for therapy response, disease relapse, and screen at risk groups for the onset of malignancy. However, such clinical utility is currently limited to breast, prostate, and colorectal cancer patients. Further understanding of the basic CTC biology of other malignancies is required to progress them towards clinical utility. Unfortunately, such basic clinical research is often limited by restrictive characterization methods and high-cost barrier to entry for CTC isolation and imaging infrastructure. As experimental clinical results on applications of CTC are accumulating, it is becoming clear that a two-tier system of CTC isolation and characterization is required. The first tier is to facilitate basic research into CTC characterization. This basic research then informs a second tier specialised in clinical prognostic and diagnostic testing. This study presented in this manuscript describes the development and application of a low-cost, CTC isolation and characterization pipeline CTC-5. This approach uses an established isolation by size approach (ScreenCell Cyto) and combines histochemical morphology stains and multiparametric immunofluorescence on the same isolated CTCs. This enables capture and characterization of CTCs independent of biomarker-based pre-selection and accommodates both single CTCs and clusters of CTCs. Additionally, the developed open-source software is provided to facilitate the synchronization of microscopy data from multiple sources (httpsgithub.comCTC5). This enables high parameter histochemical and immunofluorescent analysis of CTCs with existing microscopy infrastructure without investment in CTC specific imaging hardware. Our approach confirmed by the number of successful tests represents a potential major advance towards highly accessible low-cost technology aiming at the basic research tier of CTC isolation and characterization. The biomarker independent approach facilitates closing the gap between malignancies with poorly, and well-defined CTC phenotypes. As is currently the case for some of the most commonly occurring breast, prostate and colorectal cancers, such advances will ultimately benefit the patient, as early detection of relapse or onset of malignancy strongly correlates with their prognosis.

Characterization of GATA3 and Mammaglobin in breast tumors from African American women.

GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin, and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p0.031), ER-positivity (p0.007), and PR-positivity (p0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Markers with improved specificity and sensitivity are warranted given the high prevalence of triple negative breast cancer in the group.

Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome.

Human milk is a complex mix of nutritional and bioactive components that provide complete nutrition for the infant. However, we lack a systematic knowledge of the factors shaping milk composition and how milk variation influences infant health. Here, we used multi-omic profiling to characterize interactions between maternal genetics, milk gene expression, milk composition, and the infant fecal microbiome in 242 exclusively breastfeeding mother-infant pairs. We identified 487 genetic loci associated with milk gene expression unique to the lactating mammary gland, including loci that impacted breast cancer risk and human milk oligosaccharide concentration. Integrative analyses uncovered connections between milk gene expression and infant gut microbiome, including an association between the expression of inflammation-related genes with IL-6 concentration in milk and the abundance of

A planar-polarized MYO6-DOCK7-RAC1 axis promotes tissue fluidification in mammary epithelia.

Tissue fluidification and collective motility are pivotal in regulating embryonic morphogenesis, wound healing and tumor metastasis. These processes frequently require that each cell constituent of a tissue coordinates its migration activity and directed motion through the oriented extension of lamellipodia cell protrusions, promoted by RAC1 activity. While the upstream RAC1 regulators in individual migratory cells or leader cells during invasion or wound healing are well characterized, how RAC1 is controlled in follower cells remains unknown. Here, we identify a novel MYO6-DOCK7 axis that is critical for spatially restriction of RAC1 activity in a planar polarized fashion in model tissue monolayers. The MYO6-DOCK7 axis specifically controls the extension of cryptic lamellipodia required to drive tissue fluidification and cooperative mode motion in otherwise solid and static carcinoma cell collectives. Collective motion of jammed epithelia requires myosin VI activityThe MYO6-DOCK7 axis is critical to restrict the activity of RAC1 in a planar polarized fashionMYO6-DOCK7-RAC1 activation ensures long-range coordination of movements by promoting orientation and persistence of cryptic lamellipodiaMyosin VI overexpression is exploited by infiltrating breast cancer cells.

SPEAR a Sparse Supervised Bayesian Factor Model for Multi-omic Integration.

Unsupervised factor modeling, which preserves the primary sources of data variation through low-dimensional factors, is commonly applied to integrate high-dimensional multi-omics data. However, the resulting factors are suboptimal for prediction tasks due to the separation between factor construction and prediction model learning. A supervised factor model that effectively utilizes the responses while accounting for structural heterogeneity across omics is needed. We present SPEAR, a supervised variational Bayesian framework that decomposes multi-omics data into latent factors with predictive power. The method adaptively determines factor rank, emphasis on factor structure, data relevance and feature sparsity. SPEAR improves reconstruction of underlying factors in synthetic examples and prediction accuracy of COVID-19 severity and breast cancer tumor subtypes. SPEAR is a publicly available R-package hosted at httpsbitbucket.orgkleinsteinSPEAR . jeremy.gygiyale.edu leying.guanyale.edu.

Discovery of a Vertebral Skeletal Stem Cell Driving Spinal Metastases.

Vertebral bone is subject to a distinct set of disease processes from those of long bones, notably including a much higher rate of solid tumor metastases that cannot be explained by passive blood flow distribution alone. The basis for this distinct biology of vertebral bone has remained elusive. Here we identify a vertebral skeletal stem cell (vSSC), co-expressing the transcription factors ZIC1 and PAX1 together with additional cell surface markers, whose expression profile and function are markedly distinct from those of long bone skeletal stem cells (lbSSCs). vSSCs display formal evidence of stemness, including self-renewal, label retention and sitting at the apex of their differentiation hierarchy. Lineage tracing of vSSCs confirms that they make a persistent contribution to multiple mature cell lineages in the native vertebrae. vSSCs are physiologic mediators of spine mineralization, as genetic blockade of the ability of vSSCs to generate osteoblasts results in defects in the vertebral neural arch and body. Human counterparts of vSSCs can be identified in vertebral endplate specimens and display a conserved differentiation hierarchy and stemness. Multiple lines of evidence indicate that vSSCs contribute to the high rates of vertebral metastatic tropism observed clinically in breast cancer. Specifically, when an organoid system is used to place both vSSCs and lbSSCs in an identical anatomic context, vSSC-lineage cells are more efficient than lbSSC-lineage cells at recruiting metastases, a phenotype that is due in part to increased secretion of the novel metastatic trophic factor MFGE8. Similarly, genetically targeting loss-of-function to the vSSC lineage results in reduced metastasis rates in the native vertebral environment. Taken together, vSSCs are distinct from other skeletal stem cells and mediate the unique physiology and pathology of vertebrae, including contributing to the high rate of metastatic seeding of the vertebrae.

PIC recruitment by synthetic reader-actuators to polycomb-silenced genes blocks triple-negative breast cancer invasion.

Scientists have used small molecule inhibitors and genetic knockdown of gene-silencing polycomb repressive complexes (PRC12) to determine if restoring the expression of tumor suppressor genes can block proliferation and invasion of cancer cells. A major limitation of this approach is that inhibitors can not restore key transcriptional activators that are mutated in many cancers, such as p53 and members of the BRAF SWISNF complex. Furthermore, small molecule inhibitors can alter the activity of, rather than inhibit, the polycomb enzyme EZH2. While chromatin has been shown to play a major role in gene regulation in cancer, poor clinical results for polycomb chromatin-targeting therapies for diseases like triple-negative breast cancer (TNBC) could discourage further development of this emerging avenue for treatment. To overcome the limitations of inhibiting polycomb to study epigenetic regulation, we developed an engineered chromatin protein to manipulate transcription. The synthetic reader-actuator (SRA) is a fusion protein that directly binds a target chromatin modification and regulates gene expression. Here, we report the activity of an SRA built from polycomb chromodomain and VP64 modules that bind H3K27me3 and subunits of the Mediator complex, respectively. In SRA-expressing BT-549 cells, we identified 122 upregulated differentially expressed genes (UpDEGs, ≥ 2-fold activation, adjusted

Whole exome sequencing and replication for breast cancer among HispanicLatino women identifies

Breast cancer (BC) is one of the most common cancers globally. Genetic testing can facilitate screening and risk-reducing recommendations, and inform use of targeted treatments. However, genes included in testing panels are from studies of European-ancestry participants. We sequenced HispanicLatina (HL) women to identify BC susceptibility genes. We conducted a pooled BC case-control analysis in HL women from the San Francisco Bay area, Los Angeles County, and Mexico (4,178 cases and 4,344 controls). Whole exome sequencing was conducted on 1,043 cases and 1,188 controls and a targeted 857-gene panel on the remaining samples. Using ancestry-adjusted SKAT-O analyses, we tested the association of loss of function (LoF) variants with overall, estrogen receptor (ER)-positive, and ER-negative BC risk. We calculated odds ratios (OR) for BC using ancestry-adjusted logistic regression models. We also tested the association of single variants with BC risk. We saw a strong association of LoF variants in In HL women, LoF variants in