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Domain generalization in deep learning based mass detection in mammography A large-scale multi-center study.

Computer-aided detection systems based on deep learning have shown great potential in breast cancer detection. However, the lack of domain generalization of artificial neural networks is an important obstacle to their deployment in changing clinical environments. In this study, we explored the domain generalization of deep learning methods for mass detection in digital mammography and analyzed in-depth the sources of domain shift in a large-scale multi-center setting. To this end, we compared the performance of eight state-of-the-art detection methods, including Transformer based models, trained in a single domain and tested in five unseen domains. Moreover, a single-source mass detection training pipeline was designed to improve the domain generalization without requiring images from the new domain. The results show that our workflow generalized better than state-of-the-art transfer learning based approaches in four out of five domains while reducing the domain shift caused by the different acquisition protocols and scanner manufacturers. Subsequently, an extensive analysis was performed to identify the covariate shifts with the greatest effects on detection performance, such as those due to differences in patient age, breast density, mass size, and mass malignancy. Ultimately, this comprehensive study provides key insights and best practices for future research on domain generalization in deep learning based breast cancer detection.

Effectiveness of weight loss interventions in breast cancer survivors a systematic review of reviews.

Elevated body mass index (BMI) in breast cancer survivors (BCS) is associated with cancer recurrence and poorer treatment response. Guidelines recommend 5%-10% weight loss for overweight or obese BCS. To assess effectiveness of lifestyle interventions for female BCS on weight loss, BMI, body composition, health-related quality of life (HRQoL), physical functioning, psychosocial measures, biomarkers. Systematic review of reviews and meta-analyses. All clinical settings. Adult female BCS (active treatment or post-treatment). Medline, Embase, CINAHL, PsycINFO, Cochrane Library (including Database of Abstracts of Reviews of Effects) were searched for systematic reviews published in English between 1990 and 2022, with weight, BMI or body fat as primary outcome. Narrative reviews, editorials, letters, conference abstracts were excluded. Review quality was assessed using the Joanna Briggs Institute quality assessment tool. 17 reviews were included. Twelve reported significant reductions in one or more anthropometric outcomes weight -1.36 kg (95% CI-2.51 to -0.21) to -3.8 kg (95% CI -5.6 to -1.9) BMI -0.89 kgm Lifestyle interventions can significantly improve outcomes for BCS. Multimodal interventions are likely to have the greatest impact in reducing weight, BMI and body fat. Further research must define the optimal combination, intensity and duration of effective interventions. CRD42021283481.

Segregation analysis of 17,425 population-based breast cancer families Evidence for genetic susceptibility and risk prediction.

Rare pathogenic variants in known breast cancer-susceptibility genes and known common susceptibility variants do not fully explain the familial aggregation of breast cancer. To investigate plausible genetic models for the residual familial aggregation, we studied 17,425 families ascertained through population-based probands, 86% of whom were screened for pathogenic variants in BRCA1, BRCA2, PALB2, CHEK2, ATM, and TP53 via gene-panel sequencing. We conducted complex segregation analyses and fitted genetic models in which breast cancer incidence depended on the effects of known susceptibility genes and other unidentified major genes and a normally distributed polygenic component. The proportion of familial variance explained by the six genes was 46% at age 20-29 years and decreased steadily with age thereafter. After allowing for these genes, the best fitting model for the residual familial variance included a recessive risk component with a combined genotype frequency of 1.7% (95% CI 0.3%-5.4%) and a penetrance to age 80 years of 69% (95% CI 38%-95%) for homozygotes, which may reflect the combined effects of multiple variants acting in a recessive manner, and a polygenic variance of 1.27 (95% CI 0.94%-1.65), which did not vary with age. The proportion of the residual familial variance explained by the recessive risk component was 40% at age 20-29 years and decreased with age thereafter. The model predicted age-specific familial relative risks consistent with those observed by large epidemiological studies. The findings have implications for strategies to identify new breast cancer-susceptibility genes and improve disease-risk prediction, especially at a young age.

Comprehensive analysis of PLKs expression and prognosis in breast cancer.

A thorough examination of PLKs in breast cancer, including their expression and prognosis. With the help of the Oncomine database, the transcript levels of PLKs in breast cancer were examined. The changes in PLKs expression with tumor stage and indeed the relationship between PLKs expression and stage of cancer in women with breast cancer were scrutinized by using the GEPIA database. Based on Kaplan-Meier plots, breast cancer patients were assessed for their prognosis. Breast cancer gene expression and mutations were analyzed within the cBioPortal database. According to Oncomine data, PLK1 and PLK4 mRNA expression levels were dramatically elevated in breast cancer patients while PLK2 and PLK5P levels were significantly downregulated. PLK1 and PLK4 expression were discovered to be greater in breast cancer tissues than in healthy tissues following analysis of the GEPIA database (P < 0.05). High levels of PLK1 and PLK4 transcripts have been linked to poor relapse-free survival rates across all patients with breast cancer according to the Kaplan-Meier Plotter database. The high levels of PLK2, PLK3, and PLK5 were associated with a higher recurrence-free survival rate. In the cBioPortal database, PLK was altered in 9.6% of breast cancer samples. Genetic alterations occurred in 15.07% of clinically counted invasive breast cancers, with mutations in 4.11%, gene amplifications in 9.59%, and gene deletion mutations in 1.37%. Additionally, the KEGG database demonstrates that PLKs are crucial for the cell cycle. The findings imply that elevated PLK1 and PLK4 expression in tissues of breast cancer might contribute significantly to the carcinogenesis of breast cancer. Moreover, PLK1 and PLK4 are highly expressed in breast cancer, and their use as molecular markers to identify high-risk subsets from patients with breast cancer is potentially possible. For the precise therapy of breast cancers, PLK1 and PLK4 are potential targets, while PLK2, PLK3, and PLK5 are brand-new biomarkers for predicting the prognosis of breast cancer.

Safety and efficacy of ribociclib plus letrozole in patients with HR, HER2- advanced breast cancer Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial.

Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone. CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1. A total of 526 patients were evaluated (median follow-up 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade ≥3 adverse events (AEs) were 99.0% and 76.2%, respectively 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade ≥3 neutropenia and anemia. Efficacy results were consistent with the global study. Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR, HER2- ABC, including populations of interest (NCT02941926). ClinicalTrials.gov NCT02941926.

Dose-enhancement of MCF 7 cell line radiotherapy using silica-iron oxide nanocomposite.

Cancer radiotherapy is one of the most effective regimens of cancer treatments, but cancer cell radioresistance remains a concern. Radiosensitizers can selectively improve the efficacy of radiotherapy and reduce inherent damage. The purpose of this work is to evaluate the effect of silica-coated iron oxide magnetic nanoparticles (SIONPs) as a radiosensitizer and compare their therapeutic effect with that of Iron oxide magnetic nanoparticles (IONPs). IONPs and SIONPs were characterized using several physical techniques such as a transmission electron microscope (TEM) and Vibrating sample magnetometer (VSM). MTT and DNA double-strand breaks (Comet) assays have been used to detect the cytotoxicity, cell viability, and DNA damage of MCF-7 cells, which were treated with different concentrations of prepared nanoparticles and exposed to an X-ray beam. In this study, an efficient radiosensitizer, SIONPs, was successfully prepared and characterized. With 0.5 Gy dose, dose enhancement factor (DEF) values of cells treated with 5 and 10 μgml of IONPs were 1 and 1.09, respectively, while those treated with SIONPs at these concentrations had DEF of 1.21 and 1.32, respectively. Results demonstrated that SIONPs provide a potential for improving the radiosensitivity of breast cancer.

CD59-Regulated Ras Compartmentalization Orchestrates Antitumor T-cell Immunity.

T cell-mediated immunotherapy represents a promising strategy for cancer treatment however, it has achieved satisfactory clinical responses in only a limited population. Thus, a broader view of the T-cell immune response is required. The RasMAPK pathway operates in many important signaling cascades and regulates multiple cellular activities, including T-cell development, proliferation, and function. Herein, we found that the typical membrane-bound complement regulatory protein CD59 is located intracellularly in T cells and that the intracellular form is increased in the T cells of patients with cancer. When intracellular CD59 is abundant, it facilitates Ras transport to the inner plasma membrane via direct interaction in contrast, when CD59 is insufficient or deficient, Ras is arrested in the Golgi, thus enhancing RasMAPK signaling and T-cell activation, proliferation, and function. mCd59ab deficiency almost completely abolished tumor growth and metastasis in tumor-bearing mice, in which CD4 and CD8 T cells were significantly increased compared with their proportions in wild-type littermates, and their proportions were inversely correlated with tumor growth. Using bone marrow transplantation and CD4 and CD8 T-cell depletion assays, we further demonstrated the critical roles of these cells in the potent antitumor activity induced by mCd59ab deficiency. Reducing CD59 expression also enhanced MAPK signaling and T-cell activation in human T cells. Therefore, the subcellular compartmentalization of Ras regulated by intracellular CD59 provides spatial selectivity for T-cell activation and a potential T cell-mediated immunotherapeutic strategy.

Development of T-cell engagers selective for cells co-expressing two antigens.

T cell-engaging bispecific antibodies (TCEs) are clinically effective treatments for hematological cancers. While the utility of TCEs in solid malignancies is being explored, toxicities arising from antigen expression on normal tissues have slowed or halted several clinical trials. Here, we describe the development of TCEs that preferentially drive T cell-mediated death against target cells co-expressing two tumor-associated antigens. We show that Ly6E and B7-H4 are simultaneously expressed on approximately 50% of breast cancers, whereas normal tissue expression is limited and mostly orthogonal. Traditional bispecific TCEs targeting a singular antigen, either Ly6E or B7-H4, are active when paired with high-affinity CD3-engagers, but normal tissue expression presents a toxicity risk. Treatment with a murine cross-reactive B7-H4-TCE results in rapid and severe weight loss in mice along with damage to B7-H4-expressing tissues. To overcome on-target toxicity, we designed trispecific antibodies co-targeting Ly6E, B7-H4,

Epithelial-to-Mesenchymal Transition Supports Ovarian Carcinosarcoma Tumorigenesis and Confers Sensitivity to Microtubule Targeting with Eribulin.

Ovarian carcinosarcoma (OCS) is an aggressive and rare tumor type with limited treatment options. OCS is hypothesized to develop via the combination theory, with a single progenitor resulting in carcinomatous and sarcomatous components, or alternatively via the conversion theory, with the sarcomatous component developing from the carcinomatous component through epithelial-to-mesenchymal transition (EMT). In this study, we analyzed DNA variants from isolated carcinoma and sarcoma components to show that OCS from 18 women is monoclonal. RNA sequencing indicated that the carcinoma components were more mesenchymal when compared with pure epithelial ovarian carcinomas, supporting the conversion theory and suggesting that EMT is important in the formation of these tumors. Preclinical OCS models were used to test the efficacy of microtubule-targeting drugs, including eribulin, which has previously been shown to reverse EMT characteristics in breast cancers and induce differentiation in sarcomas. Vinorelbine and eribulin more effectively inhibited OCS growth than standard-of-care platinum-based chemotherapy, and treatment with eribulin reduced mesenchymal characteristics and N-MYC expression in OCS patient-derived xenografts. Eribulin treatment resulted in an accumulation of intracellular cholesterol in OCS cells, which triggered a downregulation of the mevalonate pathway and prevented further cholesterol biosynthesis. Finally, eribulin increased expression of genes related to immune activation and increased the intratumoral accumulation of CD8 T cells, supporting exploration of immunotherapy combinations in the clinic. Together, these data indicate that EMT plays a key role in OCS tumorigenesis and support the conversion theory for OCS histogenesis. Targeting EMT using eribulin could help improve OCS patient outcomes. Genomic analyses and preclinical models of ovarian carcinosarcoma support the conversion theory for disease development and indicate that microtubule inhibitors could be used to suppress EMT and stimulate antitumor immunity.

A preliminary, prospective study of peripheral neuropathy and cognitive function in patients with breast cancer during taxane therapy.

Dramatic improvements in cancer survival have occurred in the last decade, but the quality of life for many survivors is compromised due to severe, long-lasting, and often irreversible side effects of chemotherapy. The neurological side effects, chemotherapy induced peripheral neuropathy (CIPN) and cancer relatedinduced cognitive impairment (CRCICICI), are under-recognized and can occur after chemotherapy, immunotherapy, or radiation. The cellular mechanisms underlying these neurological side effects are poorly understood and there are no effective treatments or preventions, other than reduction or termination of cancer therapy. In our preliminary prospective, non-interventional study to examine the side effects of chemotherapy in patients with breast cancer (NCT03872141), patients with breast cancer who received standard of care single agent weekly taxane-based chemotherapy were assessed at baseline, midpoint, and end of treatment for neurological and cognitive changes and for blood levels of potential protein biomarkers (n 13). CIPN and CRCI both showed an increase in severity with accumulating taxane and these changes were compared to protein alternations over the course of treatment. Using peripheral blood collected from patients (n 10) during chemotherapy and tested with an antibody array curated by the MD Anderson RPPA Core), we found that 19 proteins were increased, and 12 proteins decreased over 12 weeks of treatment. Among those downregulate were proteins known to be critical for neuronal viability and function including GRB2 (growth factor receptor-bound protein 2) and NCS1 (neuronal calcium sensor 1). Concurrently, proteins associated with apoptosis, including BAK1 (Bcl-1 homologous antagonistkiller), were upregulated. These results support the proposal that CIPN and CRCI increase with increasing taxane exposure, and identified several proteins that are altered with taxane exposure that could be implicated in their pathogenesis. In conclusion, our study provides evidence for progressive neurological changes and the rationale to investigate the molecular basis for these changes with the goal of target identification for mitigation of these neurological side effects.

Effectiveness of combined nutrition and exercise interventions on body weight, lean mass, and fat mass in adults diagnosed with cancer a systematic review and meta-analysis.

Changes in body weight and composition (fat and lean mass) are prominent side effects of cancer treatment. Nutrition and exercise interventions are both key strategies to protect against these adverse effects, yet their impact when combined has not been comprehensively reviewed in adults with cancer. This systematic review and meta-analysis aims to assess the effects of combined nutrition and exercise interventions on body weight and composition in adults with cancer. Four databases were searched until January 2021. Combined nutrition and exercise randomized controlled trials that detailed the nutrition and exercise prescription and reported body weight and composition outcomes were eligible. Risk of bias was assessed through the Cochrane Collaboration tool. The number of participants, mean values, and standard deviations of the outcome variables were extracted. Mean differences (MDs) were pooled using random-effects models. Predetermined subgroup analyses included cancer type, intervention intent, exercise modality, and use of behavior change strategies. Twenty-three RCTs were included. Nutrition plus exercise interventions significantly reduced body weight (MD - 2.13 kg 95%CI, - 3.07 to - 1.19), fat mass (MD - 2.06 kg 95%CI, - 3.02 to - 1.09), and lean mass (MD - 0.43 95%CI, - 0.82 to - 0.04). Subgroup analyses in women with breast cancer showed that weight loss interventions and interventions incorporating behavior change strategies significantly reduced body weight and fat mass but also reduced lean mass. Interventions aiming to maintain body weight showed no changes in body weight, as intended. Combined nutrition and exercise interventions successfully reduce body weight and fat mass in adults with cancer but also reduce lean mass. In contrast, weight loss-focused interventions are associated mostly with reduced lean mass. PROSPERO registration number CRD42020161805.

The Cancer Genomic Integration Model for Symptom Science (CGIMSS) A Biopsychosocial Framework.

Current nursing research has characterized symptom clusters and trajectories in individuals with breast cancer. The existing literature describes the relationship between symptoms and biological variables and the potential moderating effects of individual and social factors. The genomic profiling of breast cancer has also been an area of much recent research. Emerging evidence indicates that incorporating cancer genomics into symptom science research can aid in the prognostication of symptoms and elucidate targets for symptom management interventions. The aim of this paper is to outline a model to integrate cancer genomics into symptom science research, illustrated using breast cancer and psychoneurological (PN) symptoms as an example. We present a review of the current literature surrounding breast cancer genomics (specifically cancer genomic instability) and the biological underpinnings of the PN symptom cluster. Advances in both of these areas indicate that inflammation may serve as the bridge between cancer genomics and the PN symptom cluster. We also outline how the integration of cancer genomics into symptom science research synergizes with current research of individual and social factors in relation to symptoms. This model aims to provide a framework to guide future biopsychosocial symptom science research that can elucidate new predictive methods and new targets for intervention.

A case of clinically malignant rapid-progressive cardiac myxoma after COVID-19 infection.

This article presents a clinical case of urgent, life-saving surgical intervention in a 69-year-old woman with left atrial myxoma with rapid morphological and clinical progression and a history of COVID-19 and breast cancer in remission. However, the concurrent (perhaps secondary) thrombophilic condition facilitated the complication development in the form of superior vena caval orifice thrombosis in the early postoperative period. For this complication, repeated surgery in the volume of thrombectomy was performed, which resulted in stabilization of the patients condition.

Pretreatment platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as a predictor of pathological complete response to neoadjuvant chemotherapy in patients with breast cancer single center experience from Turkey.

The aim of this study was to investigate the predictive value of PLR and NLR as an indicator of pathological complete response (pCR) in patients with breast cancer after NACT. One hundred thirty-nine patients with early or LABC and candidates to NACT were retrospectively analyzed. The prognostic significance of PLR and NLR was analyzed. In addition, predictive indicators of pCR to NACT were also evaluated. pCR was obtained in 48.9% of patients. Significant difference was detected between pCR and PLR, tumor grade, clinical lymph node status and molecular subgroup. The higher rate of pCR was significantly achieved for patients with PLR low ( < 181.7) compared with those with PLR high (>181.7) (68.6% vs. 33.4% P < 0.001). PLR, tumor grade and pCR to NACT for disease-free survival (DFS), and PLR, NLR, tumor grade and pCR to NACT for overall survival were detected to be prognostic factors by univariate analysis. On the other hand, a logistic regression analysis indicated that PLR and NLR were found to be an independent factors for predicting pCR to NACT ( P < 0.001 OR, 0.07 95% CI, 0.02-0.25 and P 0.016 OR, 4.66 95% CI, 1.33-16.2, respectively), as were molecular subtypes ( P 0.001 OR, 0.23 95% CI, 0.09-0.56). Our results showed that PLR low and NLR low before NACT are readily feasible and simple and also inexpensive biomarkers predicting pCR to NACT for patients with LABC.

Current and emerging options for patients with melanoma brain metastases.

Melanoma is the most aggressive skin cancer, with a high incidence of metastatic spread and a predilection for metastases to the brain. It represents the third most common origin of brain metastases after breast and lung cancer. With the advent of targeted therapy and immunotherapy in melanoma, along with improved local therapy options such as stereotactic radiosurgery (SRS), the treatment of melanoma brain metastases (MBM) has led to significant improvements in outcome. In this review, we provide an overview of management options for patients with MBM while highlighting emerging treatment options. Surgery may be considered for patients with symptomatic MBM, whereas SRS is considered standard for patients with 1 to 4 brain lesions. Combination immunotherapy has led to durable intracranial responses and improved long-term outcomes for patients with asymptomatic MBM. The data available to date have shown that patients with MBM can have a durable response and overall response that are similar to those of patients without brain metastases, and additional trials are ongoing. Mounting evidence suggests that patients with MBM should be considered for inclusion in clinical trials, which range from early-phase trials to phase 3 studies, to accelerate much-needed drug development in this population.

Racial-ethnic variations in phyllodes tumors among a multicenter United States cohort.

Previous studies have identified racial-ethnic differences in the diagnostic patterns and recurrence outcomes of women with phyllodes tumors (PT). However, these studies are generally limited in size and generalizability. We therefore sought to explore racial-ethnic differences in age, tumor size, subtype, and recurrence in a large US cohort of women with PT. We performed an 11-institution retrospective review of women with PT from 2007 to 2017. Differences in age at diagnosis, tumor size and subtype, and recurrence-free survival according to race-ethnicity. Women of non-White race or Hispanic ethnicity were younger at the time of diagnosis with phyllodes tumor. Non-Hispanic Other women had a larger proportion of malignant PT. There were no differences in recurrence-free survival in our cohort. Differences in age, tumor size, and subtype were small. Therefore, the workup of young women with breast masses and the treatment of women with PT should not differ according to race-ethnicity. These conclusions are supported by our finding that there were no differences in recurrence-free survival.

Prevalence of Local Postoperative Complications and Breast Implant Illness in Women With Breast Implants.

It is unknown how often breast implant illness (BII) is the indication for revision in women with silicone breast implants. To examine how often women with silicone breast implants have their implants explanted or replaced because of BII compared with local postoperative complications. A legacy cohort study on breast implant revision surgery was conducted between April 1, 2015, and December 31, 2020, and a prospective cohort study on breast implantation and revision surgery was conducted between April 1, 2015, and December 31, 2019 (with follow-up until December 31, 2020). Data were obtained from the Dutch Breast Implant Registry. Data analysis was performed from September 2021 to August 2022. Silicone breast implant. Breast implant revision with the indication BII or local postoperative complications. All 12 882 cosmetic breast implants (6667 women mean SD age, 50.6 12.7 years) and 2945 reconstructive breast implants (2139 women, mean SD age, 57.9 11.3 years) in the legacy cohort and all 47 564 cosmetic breast implants (24 120 women, mean SD age, 32.3 9.7 years) and 5928 reconstructive breast implants (4688 women, mean SD age, 50.9 11.5 years) in the prospective cohort were included for analysis. In the prospective cohort, 739 cosmetic breast implants (1.6%) were revised after a median (IQR) time to reoperation of 1.8 (0.9-3.1) years, and 697 reconstructive breast implants (11.8%) were revised after a median (IQR) time to reoperation of 1.1 (0.5-1.9) years. BII was registered as the reason for revision in 35 cosmetic revisions (4.7%) and 5 reconstructive revisions (0.7%) in the prospective cohort, corresponding to 0.1% of the inserted implants. In the legacy cohort, 536 cosmetic revisions (4.2%) and 80 reconstructive breast implant revisions (2.7%) were performed because of BII. In this cohort study of women with silicone breast implants, BII was an uncommon indication for revision compared with local complications, both in the short and long term. In contrast to the increasing public interest in BII, these results showed that local complications are a far more common reason for breast implant revision.

Spirituality and financial toxicity among Hispanic breast cancer survivors in New Jersey.

Cancer survivors often incur significant out-of-pocket costs this can result in financial toxicity, defined as the adverse financial impact of cancer due to direct or indirect costs related to the disease. There has been little research on whether spirituality is associated with the experience of financial toxicity. In this study, we tested the hypothesis that spirituality would be inversely associated with financial toxicity. We evaluated these associations in a cross-sectional study of Hispanic breast cancer survivors (n 102) identified through the New Jersey State Cancer Registry. Participants completed the FACIT-Sp-12, which has two spirituality subscales (meaningpeace faith). Financial toxicity was assessed using the 11-item COST measure lower scores suggest worse toxicity. In multivariable linear regression analyses, we examined the associations between spirituality scores and financial toxicity, adjusting for age, race, education, household income, and insurance status. The spirituality total score (β 0.49, 95% confidence interval (CI) 0.17, 0.8), meaningpeace subscale score (β 0.71, 95% CI 0.12, 1.31), and faith (β 0.71, 95% CI 0.2, 1.21) subscale score were all inversely associated with financial toxicity. Spirituality may be an important factor in ameliorating the detrimental effects of financial toxicity among Hispanic breast cancer survivors and should be considered in interventions for financial toxicity in this population.

Unmet supportive care needs of caregivers according to medical settings of cancer patients a cross-sectional study.

The objectives of this study were to compare the unmet supportive care needs (SCN) of caregivers and describe the 10 most frequent of them according to various cancer settings phase of cancer care pathway (i.e., treatment vs. follow-up), cancer site (i.e., breast, digestive, or lung cancer), and cancer status (i.e., metastatic vs. non-metastatic). Participants completed a self-reported questionnaire to assess their unmet SCN (SCNS-PC). According to their cancer settings, non-parametric ANOVA or Mann-Whitney tests were performed to compare the SCNS-PC scores. The prevalence of caregivers with unmet SCN was described using percentages. Among 583 participants, 516 caregivers (88.5%) completed the SCNS-PC questionnaire. Most patients had digestive (47.3%), non-metastatic cancer (67.6%) and were recruited during the follow-up phase (56.2%). The results revealed no significant difference in SCNS-PC scores according to cancer settings except for caregivers of patients with metastatic cancer, who reported more unmet SCN related to health care service and information needs. The more qualitative item per item analysis seems to indicate the existence of five frequently unsatisfied SCN across situations, especially concerns about the recurrence and reduction of stress in patients, with variable ranking among the most unmet SCN. Although there was no significant difference in unmet SCN scores between medical settings, examining the prevalence of unmet SCN helps identify the issues to focus on when supporting caregivers and developing dedicated consultations or interventions for them.

Knockdown of circ-ADAM9 inhibits malignant phenotype and enhances radiosensitivity in breast cancer cells via acting as a sponge for miR-383-5p.

Circular RNA (circRNA) has been proven to play a critical role in breast cancer progression. Therefore, this study was designed to clarify the role and underlying molecular mechanisms of circ-disintegrin and metalloproteinase 9 (circ-ADAM9) in breast cancer. A quantitative real-time polymerase chain reaction (RT-qPCR) was conducted to assess the expression levels of circ-ADAM9, microRNA-383-5p (miR-383-5p), and profilin 2 (PFN2). Cellular growth curves of breast cancer cells were determined by colony-forming assay. Cell viability and apoptosis were measured by MTT and flow cytometry, respectively. The protein expression level was analyzed by western blot. Cell migration and invasion were evaluated by wound healing and Transwell assays. A xenograft experiment was established to clarify the functional role of circ-ADAM9 inhibition in vivo. The interactions among circ-ADAM9, miR-383-5p, and PFN2 were analyzed by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. We found that circ-ADAM9 was upregulated in breast cancer tissues and cells compared to controls. Inhibition of circ-ADAM9 expression impaired proliferation, migration, and invasion, but increased radiosensitivity and apoptosis in breast cancer cells besides, radiotherapy combined with circ-ADAM9 inhibition showed significant inhibitory effects on tumor growth. The functional effects of circ-ADAM9 were related to miR-383-5p, a target of circ-ADAM9. Overexpression of miR-383-5p-mediated malignant behaviors and radiosensitivity of breast cancer cells were dependent on PFN2. Circ-ADAM9 was found to participate in breast cancer progression through targeting the miR-383-5pPFN2 axis.

Low Rates of Lung and Colorectal Cancer Screening Uptake Among a Safety-net Emergency Department Population.

A suspected diagnosis of cancer through an emergency department (ED) visit is associated with poor clinical outcomes. The purpose of this study was to explore the rate at which ED patients attend cancer screenings for lung, colorectal (CRC), and breast cancers based on national guidelines set forth by the United States Preventive Services Task Force (USPSTF). This was a prospective cohort study. Patients were randomly approached in the Eskenazi Hospital ED between August 2019-February 2020 and were surveyed to determine whether they would be eligible and had attended lung, CRC, and breast cancer screenings, as well as their awareness of lung cancer screening with low-dose computed tomography (LDCT). Patients who were English-speaking and ≥18 years old, and who were not critically ill or intoxicated or being seen for acute decompensated psychiatric illness were offered enrollment. Enrolled subjects were surveyed to determine eligibility for lung, colorectal, and breast cancer screenings based on guidelines set by the USPSTF. No cancer screenings were actually done during the ED visit. A total of 500 patients were enrolled in this study. More participants were female (54.4%), and a majority were Black (53.0%). Most participants had both insurance (80.2%) and access to primary care (62.8%). Among the entire cohort, 63.0% identified as smokers, and 62.2% (140225) of the 50- to 80-year-old participants qualified for lung cancer screening. No patients were screened for lung cancer in this cohort (0225). Only 0.6% (3500) were aware that LDCT was the preferred method for screening. Based on pack years, 35.5% (3290) of the patients who were 40-49 years old and 6.7% (690) of those 30-39 years old would eventually qualify for screening. Regarding CRC screening, 43.6% (218500) of the entire cohort was eligible. However, of those patients only 54% (118218) had been screened. Comparatively, 77.7% (87112) of the eligible females had been screened for breast cancer, but only 54.5% (61112) had been screened in the prior two years. Many ED patients are not screened for lungcolorectalbreast cancers even though many are eligible and have reported access to primary care. This study demonstrates an opportunity and a need to address cancer screening in the ED.

Provider discussion of genetic counseling among high-risk Spanish-preferring Latina breast cancer survivors.

Among high-risk breast cancer (BC) survivors, genetic counseling (GC) and genetic testing (GT) may inform cascade testing and risk management. Compared to non-Hispanic White BC survivors, Spanish-preferring Latina BC survivors are less likely to report discussing GC with a healthcare provider. However, few studies have examined Latinas experiences with GCGT, particularly outside of the mainland USA. This study aimed to compare frequency of provider discussion of GC between Spanish-preferring Latina BC survivors living in Florida (FL) and Puerto Rico (PR). We conducted secondary data analysis of baseline assessments from a randomized pilot of an educational intervention for Spanish-preferring Latina BC survivors. Participants (N 52) were GCGT-naive, but met clinical criteria for GCGT referral. Participants self-reported sociodemographic, clinical, and cultural variables, including previous provider discussion of GC. Descriptive statistics characterized frequency of GC discussion. Logistic regression examined the relationships between sociodemographic, clinical, and cultural characteristics and GC discussion. Only 31% of participants reported previous GC discussion. More participants from PR reported having GC discussions (43% vs. 21% in the mainland USA). In multivariable analyses, greater likelihood of GC discussion was associated with PR (vs. mainland USA) residence (odds ratio OR 6.00, p .03), older age at baseline (OR 1.19, p .04), and younger age at BC diagnosis (OR 0.80, p .03). Few high-risk Spanish-preferring Latina BC survivors in the mainland USA and PR had discussed GC with their providers. These results highlight a gap in the implementation of evidence-based genetics guidelines. Provider-directed interventions may be needed to increase uptake of GCGT among Latina BC survivors. Some families have changes in the BRCA genes that increase their risk for developing breast cancer compared to those who do not have these gene changes. Through genetic testing, we can identify breast cancer survivors who have these gene changes so their families can take action to prevent future cancers. Breast cancer survivors who are diagnosed at a young age, or who have a strong family history of breast and ovarian cancer, are eligible for genetic counseling and BRCA testing. Yet, compared to women from other racial and ethnic groups, fewer Latina breast cancer survivors have genetic counseling and testing. This study explored frequency of healthcare providers’ discussion about genetic counseling among Spanish-preferring Latina breast cancer survivors living in Florida and Puerto Rico. Although all participants were eligible, only 3 out of 10 indicated that a provider previously discussed genetic counseling with them. Participants who were living in Puerto Rico, older at study entry, or younger at the time of their breast cancer diagnosis were more likely to have discussed genetic counseling with a healthcare provider. Healthcare providers are important for identifying and referring high-risk Spanish-preferring Latinas for genetic counseling in and outside the mainland USA.

Genome Reporting for Healthy Populations-Pipeline for Genomic Screening from the GENCOV COVID-19 Study.

Genome sequencing holds the promise for great public health benefits. It is currently being used in the context of rare disease diagnosis and novel gene identification, but also has the potential to identify genetic disease risk factors in healthy individuals. Genome sequencing technologies are currently being used to identify genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS-CoV-2. The GENCOV study aims to look at the relationship between genetic, serological, and biochemical factors and variability of SARS-CoV-2 symptom severity, and to evaluate the utility of returning genome screening results to study participants. Study participants select which results they wish to receive with a decision aid. Medically actionable information for diagnosis, disease risk estimation, disease prevention, and patient management are provided in a comprehensive genome report. Using a combination of bioinformatics software and custom tools, this article describes a pipeline for the analysis and reporting of genetic results to individuals with COVID-19, including HLA genotyping, large-scale continental ancestry estimation, and pharmacogenomic analysis to determine metabolizer status and drug response. In addition, this pipeline includes reporting of medically actionable conditions from comprehensive gene panels for Cardiology, Neurology, Metabolism, Hereditary Cancer, and Hereditary Kidney, and carrier screening for reproductive planning. Incorporated into the genome report are polygenic risk scores for six diseases-coronary artery disease atrial fibrillation type-2 diabetes and breast, prostate, and colon cancer-as well as blood group genotyping analysis for ABO and Rh blood types and genotyping for other antigens of clinical relevance. The genome report summarizes the findings of these analyses in a way that extensively communicates clinically relevant results to patients and their physicians. © 2022 Wiley Periodicals LLC. Basic Protocol 1 HLA genotyping and disease association Basic Protocol 2 Large-scale continental ancestry estimation Basic Protocol 3 Dosage recommendations for pharmacogenomic gene variants associated with drug response Support Protocol System setup.

Quantitative Assessment of Restriction Spectrum MR Imaging for the Diagnosis of Breast Cancer and Association With Prognostic Factors.

Restriction spectrum imaging (RSI) is an advanced quantitative diffusion-weighted magnetic resonance imaging (DWI) technique to assess breast cancer. To investigate the ability of RSI to differentiate the benign and malignant breast lesions and the association with prognostic factors of breast cancer. Retrospective. Seventy women (mean age, 49.6 ± 12.3 years) with 56 malignant and 19 benign breast lesions. 3-T RSI-based DWI sequence with echo-planar imaging technique. The apparent diffusion coefficient (ADC) and RSI parameters (restricted diffusion f Mann-Whitney U test or Students t-test was applied to compare the quantitative parameters between the different groups. Intraclass correlation coefficient (ICC) was used to assess readers reproducibility. Binary logistic regression was used to combine parameters. Area under the curve (AUC) of receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of parameters to distinguish benign from malignant breast lesions. A P-value <0.05 was considered statistically significant. Malignant breast lesions showed significantly lower ADC and f The RSI-derived parameters (f 4 TECHNICAL EFFICACY Stage 2.

Alternatives to wire localization of non-palpable breast lesions.

With the introduction of screening mammography, the proportion of smaller, clinically recognised tumors has increased. In cases in which lesions cannot be palpated, a guidewire or a wireless marker is placed. Wire localization is associated with several limitations, despite its status as gold standard. Several wireless methods that meet these limitations have been developed. Methods that increase efficiency and patient satisfaction. This review provides an overview of the existing literature on intra-operative localization methods, and the risk of re-resection associated with excision of non-palpable mammary lesions.

A tumor-suppressive function for Notch3 in the parous mammary gland.

Notch3 promotes mammary luminal cell specification and forced Notch3 activation can induce mammary tumor formation. However, recent studies suggest a tumor-suppressive role for Notch3. Here, we report on Notch3 expression and functional analysis in the mouse mammary gland. Notch3 is expressed in the luminal compartment throughout mammary gland development, but switches to basal cells with initiation of post-lactational involution. Deletion of Notch3 caused a decrease of Notch activation in luminal cells and diminished luminal progenitors at puberty, as well as reduced alveolar progenitors during pregnancy. Parous Notch3-- mammary glands developed hyperplasia with accumulation of CD24hiCD49flo cells, some of which progressed to invasive tumors with luminal features. Notch3 deletion abolished Notch activation in basal cells during involution, accompanied by altered apoptosis and reduced brown adipocytes, leading to expansion of parity-identified mammary epithelial cells (PI-MECs). Interestingly, the postpartum microenvironment is required for the stem cell activity of Notch3-- PI-MECs. Finally, high expression of NOTCH3 is associated with prolonged survival in patients with luminal breast cancer. These results highlight an unexpected tumor-suppressive function for Notch3 in the parous mammary gland through restriction of PI-MEC expansion.

Developing theory-driven narrative messages with personal stories A step-by-step guide.

Narratives are commonly utilized in health promotion and behavior change interventions due to their efficacy over didactic or expository interventions. While grounding narratives in behavioral theory may render them more effective, balancing the integration of theoretical and creative aspects of the narrative development process while maintaining authenticity is challenging. Thus, this manuscript describes a rigorous process through which researchers can intentionally integrate theory and personal stories for health interventions. The process for creating theory-driven narratives involves the following steps (1) defining the purpose of the narratives, (2) selecting a guiding theory, (3) collecting personal testimonials, (4) immersing self into testimonials, (5) identifying central narratives and important variations, (6) considering additional theories, (7) piecing quotes into cohesive stories, (8) filling in the gaps, and (9) checking for resonance. To exemplify this step-by-step process, we provide a case study from our research involving the development of a psychoeducational intervention to model information seeking strategies for managing cancer-related uncertainty among women who have recently tested positive for pathogenic genetic variants that increase risk for hereditary breast and ovarian cancer. We discuss special considerations for developing theory-driven narrative interventions and reflect on how this rigorous step-by-step process can be adapted by other researchers.

Haptoglobin genotypes and malaria comorbidity in breast cancer and healthy Nigerian women.

Breast cancer is the leading cause of mortality among women, with over a million cases recorded globally. Haptoglobin (Hp) protein and genotypes play important roles in cancer predisposition and progression, but studies have reported varying outcomes in populations. The association of Hp genotypes in breast cancer patients with malaria has not been investigated in Nigerians, which is the aim of our study. In healthy women (control n 279) and clinically diagnosed breast cancer patients (breast cancer n 70). Haptoglobin genotypes and Plasmodium falciparum cyclooxygenase III genes were detected by polymerase chain reaction (PCR). Proportions were compared, and the test of association was carried out with a significance level set at P < 0.05. Overall, 311 of 349 (89%) individuals had malaria infection with similar proportions in breast cancer (63 of 70) and healthy control group (248 of 279) malaria incidence was, however, lower in Hp 2-2 breast cancer patients (P 0.04). The prevalence of Hp genotypes was Hp 1-1 (78.2%), Hp 2-1 (7.2%), and 2-2 (14.6%). In breast cancer groups, Hp 2-2 genotype was significantly lower with 3 (4.2%) of 70 vs. 48 (17.2%) of 279 in control group (P 0.006). The results of the study show low Hp 2-2 genotype relative to other genotypes in breast cancer patients we conclude that low Hp 2-2 genotype is associated with lower malaria risk in breast cancer Nigerian women. It is important to further understand the roles malaria, Hp, and other genotypes play in the pathogenesis of aggressive breast cancer commonly seen in Nigerian women.

Correlation analysis of body image level and female sexual dysfunction in young patients with postoperative breast cancer.

To determine the relationship between female body image and female sexual dysfunction (FSD) in young patients (20-40 years) with postoperative breast cancer. Using the convenient sampling method, we identified 276 young patients with postoperative breast cancer from June 2017 to 2019 in the Department of Oncology and Radiotherapy of the First Affiliated Hospital of Anhui Medical University to be included in the study. A general situation questionnaire for body image scale (BIS) and female sexual function index (FSFI) scale was used to evaluate the correlation between body image level and the prevalence of FSD in young patients with postoperative breast cancer. The total score for BIS was 10.98 ± 7.19, indicating that patients were moderately dissatisfied with their body image The total prevalence of FSD was 63.41%. Pearson correlation analysis showed a negative correlation between the total score, each dimension score of BIS, total FSD, and the incidence of each dimension disorder (range, r -0.414 to -0.717, all P values <0.05). There is a negative correlation between the body image level and the prevalence of FSD in young patients with postoperative breast cancer. This suggests that clinical medical workers should develop an intervention plan to improve the body image level of postoperative young breast cancer patients according to the unique physiological and psychological characteristics of these patients while also reducing the prevalence of FSD.

Intratumoral heterogeneity contributes to the chemotherapy prognosis of breast cancer.

Previous studies have shown that intratumoral heterogeneity (ITH) is associated with poor clinical outcomes and is thought to be a mechanism of resistance to chemotherapy and radiotherapy. We aimed to determine how ITH affects the response to drug therapy in breast cancer (BC). We assessed ITH using mutated allele tumor heterogeneity (MATH) data from BC patients in the TCGA database. The study enrolled 515 patients with BC treated with chemotherapy from the TCGA database who had available data on survival, whole-exome sequencing, and genome-wide transcriptome sequencing. Additionally, 399 MSK-BRCA cohort patients were treated with chemotherapy. All statistical analyses were conducted using R. All comparisons were made using the two-sided Mann-Whitney test, Pearsons Chi-squared test, and the Kruskal-Wallis test. Statistical significance was defined as P values less than 0.05 (P < 0.05). The survival package in R was used to conduct the analysis. Additional analysis was performed on 515 BC patients receiving adjuvant chemotherapy. MATH was associated with overall survival (OS) in multivariate analysis (hazard ratio (HR), 1.432 95% confidence interval, 1.073-1.913 P 0.015). Pathway enrichment and immune cell analysis revealed that the low MATH group had significantly higher infiltration of 24 different types of immune cells than the high MATH group. Individuals with low MATH scores had a longer OS than those with high MATH scores. Immune responses were significantly enhanced in breast cancer patients with low MATH scores.

Bibliometric analysis of publications on necroptosis from 2001 to 2021.

Breast manifestation of extramedullary myeloid sarcoma A case report.

Extramedullary myeloid sarcoma (MS) of the breast is a rare disease, representing 0.12% of all diagnoses of acute myeloid leukemia. We review a case of a 27-year-old female who presented with a palpable right breast mass. She subsequently underwent a biopsy, which showed breast tissue with diffuse infiltrate of blasts compatible with MS. A bone marrow biopsy was performed with no evidence of leukemia or lymphoma. Therefore, a second breast biopsy was obtained for additional testing and cytogenetics which demonstrated positive (t821)(q22q22) translocation associated with acute myeloid leukemia. Patient was admitted for induction of chemotherapy, but she subsequently developed neutropenic colitis and C. diff colitis. Unfortunately, her condition quickly deteriorated, and she passed away shortly after. This report aims to describe the clinical, radiographic, and pathological features of a case of extramedullary MS involving the breast.

The relationship between processed meat, red meat, and risk of types of cancer A Mendelian randomization study.

Observational studies have suggested processed and red meat may increase the risk of cancer. However, the causal effects and direction between them were still unclear. We conducted two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of processed meat and red meat on the risk of nine common types of cancer, namely, lung, ovarian, endometrial, breast, kidney, gastric, prostate, skin, and oropharyngeal cancer. Genome-wide association studies (GWAS) for processed meat and red meat (pork, beef, and mutton) were obtained from the UK Biobank. GWAS of types of cancer in this study were extracted from the genetic consortia and the FinnGen consortium. The inverse variance weighted (IVW) was carried out as the main method for two-sample MR analysis. Sensitivity analyses were used to assess the robustness of the results. Genetically predicted processed meat intake was causally associated with increased risk of lung cancer (OR odds ratio 1.923, 95% CI 1.084-3.409, Our results suggested that intake of processed meat may increase the risk of lung cancer. These findings provided no evidence to support that consumption of processed and red meat has a large effect on the risk of other cancers we studied. Further research is needed to clarify the results.

Risk Factors of Catheter-Related Infection in Unplanned Extubation of Totally Implantable Venous-Accessportsin Tumor Patients.

Totally implantable intravenous ports (TIVAPs) are mostly used for long-term intravenous infusion therapy in cancer patients and can be left in the body for long periods of time for easy management, making them a simple and safe infusion device. Although the risks associated with long-term retention of fully implantable IV ports are less than those associated with other intravenous catheters, various complications may still occur at the time of implantation or during long-term use. To provide a scientific basis for clinical reduction of implantable intravenous port-associated infection complications by studying the risk factors for catheter-associated infection complications in patients applying implantable intravenous ports. A retrospective study was conducted on oncology patients treated with TIVAP at our hospital between January 2017 and November 2021, with a review of patients who were unplanned for extubation. Their demographic data, underlying disease status, and surgery-related data were counted to summarize and analyze the complications and related influencing factors of implantation and postimplantation. A total of 70 individuals with a mean age of 56.49 ± 12.19 years were included in the study. Among them, 39 were male and 64 had the highest percentage of epithelial tumors, followed by tumors of the lymphopoiesis system and mesenchymal tumors with 4 and 2 cases, respectively. Forty-eight of these patients did not have their ports removed as planned due to the occurrence of catheter-related hematogenous infections. In univariate analysis, BMI and neutropenia were risk factors for catheter-associated infections. In the multivariate analysis, BMI (OR 1.38, 95% CI 1.07-1.78, The overall complication rate of fully implanted intravenous ports was high, but most complications improved with symptomatic management, and no deaths due to port complications were identified. Infection was the most common complication, with catheter-associated bloodstream infection being the most common cause of unplanned port extraction. Patients with a higher BMI were at high risk of developing implantable IV port-associated infections, which may be an independent risk factor for implantable IV port-associated infections.

Genome-wide analysis of the FOXA1 transcriptional regulatory network identifies super enhancer associated LncRNAs in tamoxifen resistance.

Breast cancer is the leading cause of death in female cancers, and whats worse, tamoxifen resistance occurs in almost 30% breast cancer patients and has seriously attenuated the therapeutic effect. It is widely studied that epigenetic regulation has played important role in the development of tamoxifen resistance. FOXA1 is a pioneer transcription factor that can translate epigenetic signature into transcription regulation and also drive genome-wide enhancer reprogramming in breast cancer. However, the chromatin super enhancer landscape orchestrated by FOXA1 and the key downstream targets of the FOXA1 oncogenic network in tamoxifen resistance remain elusive. Through analyzing the FOXA1 ChIP-seq data in tamoxifen sensitive MCF7 and tamoxifen resistant MCF7TamR cells, we show that the FOXA1 chromatin occupancy is enhanced in both the promoter and enhancer regions, and the recruitment events may be E2 dependent in both MCF7 and MCF7TamR cells. By integratively analyzing the FOXA1 ChIP-seq data and RNA-seq data of MCF7 and MCF7TamR cells, we find that the enhanced or reduced FOXA1 chromatin binding densities may synchronize the transcriptional activity in tamoxifen resistance. Besides, we identify 1003 super enhancer associated protein coding genes and five super enhancer associated lncRNAs (ATP1A1-AS1, CASC11, CASC15, KCTD21-AS1, LINC00885) in tamoxifen resistance. By KM survival analysis, we find that high expression level of ATP1A1-AS1 and its sense transcript ATP1A1 indicates favorable clinical outcome among the luminal endocrine treated breast cancer patients. Further coexpression analysis indicates that ATP1A1-AS1 is significantly correlated with ATP1A1, and RT-qPCR results show that they both are downregulated in MCF7TamR cells. Our study shows that the FOXA1 transcriptional regulatory network may promote the development of tamoxifen resistance, and identifies one super enhancer associated lncRNA ATP1A1-AS1 that may work as promising biomarker or drug target in tamoxifen resistance.

Effect of Incision Negative Pressure Wound Therapy on Donor Site Morbidity in Breast Reconstruction with Deep Inferior Epigastric Artery Perforator Flap.

The usefulness of closed incision negative pressure wound therapy (ciNPWT) has been well documented in many surgical sites, except for the donor site of the deep inferior epigastric artery perforator (DIEP) flap. The aim of this study was to evaluate the effect of ciNPWT on microsurgical breast reconstruction using a DIEP flap. Fifty-six cases of breast reconstruction with DIEP flap were included and divided into two groups based on post-surgical wound management the ciNPWT group received ciNPWT at the donor site, while the conventional group received conventional wound management. The primary outcomes were the incidence of seroma, wound dehiscence, and surgical site infection, and secondary outcomes were the time to drain removal and amount of drainage. The breast reconstruction risk assessment (BRA) score was used to evaluate the comprehensive risk in each case. Among the patient and surgical characteristics, only the BRA score (P0.02) and the time to elevate the flap (P0.02) were significantly higher and longer in the ciNPWT group, respectively. The incidence of seroma, dehiscence, and wound infection showed no significant difference between the two groups. In the subgroup analysis of patients with body mass index ≥ 25, the primary outcomes did not differ, while the secondary outcomes were significantly lower in the ciNPWT group (drainage volume, P 0.04 time to drain removal, P 0.04). ciNPWT can potentially reduce the incidence of donor site complications of DIEP flaps, especially if the comprehensive risk for post-surgical complications is considered.

Multiomic characterization and drug testing establish circulating tumor cells as an

Matching the treatment to an individual patients tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells. CTCs and metastatic cells, but not primary tumor cells, shared stochastic mutations and similar hypomethylation levels at transcription start sites. CTCs and metastatic tumor cells shared a hybrid epithelialmesenchymal transcriptome state with reduced adhesive and enhanced mobilization characteristics. We tested anti-cancer drugs on tumor cells from a metastatic breast cancer patient. CTC responses mirrored the impact of drugs on metastatic rather than primary tumors. Our multiomic and clinical anti-cancer drug response results reveal that CTCs resemble metastatic tumors and establish CTCs as an

Amygdalin as a chemoprotective agent in co-treatment with cisplatin.

Amygdalin is a naturally occurring glycoside used in traditional Chinese medicine and is known to have anti-cancer properties. Even though the anti-cancer properties of amygdalin are well known, its effect on normal cells has not been thoroughly investigated. The aim of the present study was to investigate a possible chemo-protective role of amygdalin against the cytotoxic effects of chemotherapy for normal human cells. Specifically, it was tested in combination with a strong chemotherapeutic drug cisplatin. Human non-tumorigenic MCF12F epithelial cell line, human fibroblasts cells, human breast cancer MCF7 and MDA-MB-231 cells were treated with cisplatin in a dose- and time-depended manner in the absence or presence of amygdalin. When MCF12F cells and fibroblasts underwent pre-treatment with amygdalin followed by cisplatin treatment (24 h amygdalin 24 h cisplatin), the cell viability was increased (22%,

Bioinformatics and network-based screening and discovery of potential molecular targets and small molecular drugs for breast cancer.

Accurate identification of molecular targets of disease plays an important role in diagnosis, prognosis, and therapies. Breast cancer (BC) is one of the most common malignant cancers in women worldwide. Thus, the objective of this study was to accurately identify a set of molecular targets and small molecular drugs that might be effective for BC diagnosis, prognosis, and therapies, by using existing bioinformatics and network-based approaches. Nine gene expression profiles (GSE54002, GSE29431, GSE124646, GSE42568, GSE45827, GSE10810, GSE65216, GSE36295, and GSE109169) collected from the Gene Expression Omnibus (GEO) database were used for bioinformatics analysis in this study. Two packages, LIMMA and clusterProfiler, in

The Decalcification of Cervicothoracic Spinal Metastasis of Breast Cancer Due to Discontinuation of Denosumab A Case Report.

Breast cancers frequently metastasize to bone. Several guidelines recommend denosumab to control metastasis. In the current case, denosumab allowed the calcification of cervicothoracic spinal metastases following bone decalcification by breast cancer. Six years after administration, denosumab was discontinued and the metastatic lesions became decalcified, but recalcification occurred after re-administration of denosumab. There were no reports of serious decalcification after discontinuation of denosumab. The patient was a 71-year-old woman who was unable to walk independently because of a fracture of the seventh cervical vertebra and severe spinal cord compression. After immobilization with a halo vest, posterior fixation was performed. Examination of the pathology of the breast and cervical spine revealed ductal carcinoma of the breast. After docetaxel for four months, tegafur-gimeracil-oteracil potassium (TS-1) was administered and monthly denosumab was initiated. CT showed postoperative recalcification of the cervicothoracic spine, and MRI revealed spinal cord decompression. The first occurrence of medication-related osteonecrosis of the jaw (MRONJ) occurred five years after cervicothoracic spinal surgery and the second occurrence of MRONJ occurred after six years. Denosumab was discontinued and TS-1 was resumed four months after discontinuation. Fourteen months after discontinuation of denosumab, the patient felt muscle weakness in the right upper extremity and numbness in both hands. CT showed cervicothoracic spine decalcification and MRI showed spinal cord compression. As there were no signs of recurrence in the primary lesion around the left breast, TS-1 was continued and denosumab was resumed. Three months after the re-administration of denosumab, CT showed recalcification and recovery of upper extremity muscle strength, and MRI revealed improvement in spinal cord compression.

An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer.

Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy. However, it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation. This work designed a peptide-photosensitizer conjugate (PPC), which consisted of a PD-L1 antagonist peptide (CVRARTR), an MMP-2 specific cleavable sequence, a self-assembling motif, and the photosensitizer Purpurin 18. The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection. The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites, thereby initiating the cancer-specific release of the antagonist peptide. Simultaneously, the nanospheres gradually transform into co-assembled nanofibers, which promotes the retention of the remaining parts within the tumor. In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs, which sensitize 4T1 tumor cells to immune checkpoint blockade therapy. Therefore, PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases. The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy.

Accuracy and Utility of Preoperative Ultrasound-Guided Axillary Lymph Node Biopsy for Invasive Breast Cancer A Systematic Review and Meta-Analysis.

With the acceleration of the pace of life and work, the incidence rate of invasive breast cancer is getting higher and higher, and early diagnosis is very important. This study screened and analyzed the published literature on ultrasound-guided biopsy of invasive breast cancer and obtained the accuracy and practicality of preoperative biopsy. The four databases were screened for the literature. There was no requirement for the start date of retrieval, and the deadline was July 2, 2022. Two researchers screened the literature, respectively, and included the literature on preoperative ultrasound-guided biopsy and intraoperative and postoperative pathological diagnosis of invasive breast cancer. The diagnostic data included in the literature were extracted and meta-analyzed with RevMan 5.4 software, and the bias risk map, forest map, and summary receiver operating characteristic curves (SROC) were drawn. The included 19 studies involved about 18668 patients with invasive breast cancer. The degree of bias of the included literature is low. The distribution range of true positive, false positive, true negative, and false negative in the forest map is large, which may be related to the large difference in the number of patients in each study. Most studies in the SROC curve are at the upper left, indicating that the accuracy of ultrasound-guided axillary biopsy is very high. For invasive breast cancer, preoperative ultrasound-guided biopsy can accurately predict staging and grading of breast cancer, which has important reference value for surgery and follow-up treatment.

Development and validation of nomograms for predicting overall survival and cancer specific survival in locally advanced breast cancer patients A SEER population-based study.

For patients with locally advanced breast cancer (LABC), conventional TNM staging is not accurate in predicting survival outcomes. The aim of this study was to develop two accurate survival prediction models to guide clinical decision making. A retrospective analysis of 22,842 LABC patients was performed from 2010 to 2015 using the Surveillance, Epidemiology and End Results (SEER) database. An additional cohort of 200 patients from the Binzhou Medical University Hospital (BMUH) was analyzed. The least absolute shrinkage and selection operator (LASSO) regression was used to screen for variables. The identified variables were used to build a survival prediction model. The performance of the nomogram models was assessed based on the concordance index (C-index), calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The LASSO analysis identified 9 variables in patients with LABC, including age, marital status, Grade, histological type, T-stage, N-stage, surgery, radiotherapy, and chemotherapy. In the training cohort, the C-index of the nomogram in predicting the overall survival (OS) was 0.767 95% confidence intervals (95% CI) 0.751-0.775, cancer specific survival (CSS) was 0.765 (95% CI 0.756-0.774). In the external validation cohort, the C-index of the nomogram in predicting the OS was 0.858 (95% CI 0.812-0.904), the CSS was 0.866 (95% CI 0.817-0.915). In the training cohort, the area under the receiver operator characteristics curve (AUC) values of the nomogram in prediction of the 1, 3, and 5-year OS were 0.836 (95% CI 0.821-0.851), 0.769 (95% CI 0.759-0.780), and 0.750 (95% CI 0.738-0.762), respectively. The AUC values for prediction of the 1, 3, and 5-year CSS were 0.829 (95% CI 0.811-0.847), 0.769 (95% CI 0.757-0.780), and 0.745 (95% CI 0.732-0.758), respectively. Results of the C-index, ROC curve, and DCA demonstrated that the nomogram was more accurate in predicting the OS and CSS of patients compared with conventional TNM staging. Two prediction models were developed and validated in this study which provided more accurate prediction of the OS and CSS in LABC patients than the TNM staging. The constructed models can be used for predicting survival outcomes and guide treatment plans for LABC patients.

Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination.

Human breastmilk is rich in T cells however, their specificity and function are largely unknown. We compared the phenotype, diversity, and antigen specificity of T cells in the breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 mRNA vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor (TCR) sequence overlap was limited between blood and breastmilk. Overabundan t breastmilk clones were observed in all individuals, were diverse, and contained CDR3 sequences with known epitope specificity including to SARS-CoV-2 Spike. Spike-specific TCRs were more frequent in breastmilk compared to blood and expanded in breastmilk following a third mRNA vaccine dose. Our observations indicate that the lactating breast contains a distinct T cell population that can be modulated by maternal vaccination with potential implications for infant passive protection. The breastmilk T cell repertoire is distinct and enriched for SARS-CoV-2 Spike-specificity after maternal mRNA vaccination.

Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment.

Ascorbic acid has attracted substantial attention for its potential antitumor effects by acting as an antioxidant

Erratum Risk factors of brain metastasis and prognosis in HER2-positive breast cancer A single-institution retrospective analysis from China.

This corrects the article DOI 10.3389fonc.2022.905065..

LGBTQI cancer patients quality of life and distress A comparison by gender, sexuality, age, cancer type and geographical remoteness.

There is growing acknowledgement of the psycho-social vulnerability of lesbian, gay, bisexual, transgender, queer andor intersex (LGBTQI) people with cancer. The majority of research to date has focused on cisgender adults with breast or prostate cancer. This study examined psycho-social factors associated with distress and quality of life for LGBTQI cancer patients and survivors, across a range of sexualities and gender identities, intersex status, tumor types, ages and urbanruralremote location using an intersectional theoretical framework. 430 LGBTQI people with cancer completed an online survey, measuring distress, quality of life (QOL), and a range of psycho-social variables. Participants included 216 (50.2%) cisgender women, 145 (33.7%) cisgender men, and 63 (14.7%) transgender and gender diverse (TGD) people. Thirty-one (7.2%) participants reported intersex variation and 90 (20%) were adolescents or young adults (AYA), aged 15-39. The majority lived in urban areas (54.4%) and identified as lesbian, gay or bisexual (73.7%), with 10.9% identifying as bisexual, and 10.5% as queer, including reproductive (32.4%) and non-reproductive (67.6%) cancers. Forty-one percent of participants reported high or very high distress levels, 3-6 times higher than previous non-LGBTQI cancer studies. Higher rates of distress and lower QOL were identified in TGD compared to cisgender people, AYAs compared to older people, those who identify as bisexual or queer, compared to those who identify as lesbian, gay or homosexual, and those who live in rural or regional areas, compared to urban areas. Elevated distress and lower QOL was associated with greater minority stress (discrimination in life and in cancer care, discomfort being LGBTQI, lower outness) and lower social support, in these subgroups. There were no differences between reproductive and non-reproductive cancers. For the whole sample, distress and poor QOL were associated with physical and sexual concerns, the impact of cancer on gender and LGBTQI identities, minority stress, and lack of social support. LGBTQI people with cancer are at high risk of distress and impaired QOL. Research and oncology healthcare practice needs to recognize the diversity of LGBTQI communities, and the ways in which minority stress and lack of social support may affect wellbeing.

Diagnostic value of radiomics model based on gray-scale and contrast-enhanced ultrasound for inflammatory mass stage periductal mastitisduct ectasia.

The present study aimed to investigate the clinical application value of the radiomics model based on gray-scale ultrasound (GSUS) and contrast-enhanced ultrasound (CEUS) images in the differentiation of inflammatory mass stage periductal mastitisduct ectasia (IMSPDMDE) and invasive ductal carcinoma (IDC). In this retrospective study, 254 patients (IMSPDMDE 129 IDC125) were enrolled between January 2018 and December 2020 as a training cohort to develop the classification models. The radiomics features were extracted from the GSUS and CEUS images. The least absolute shrinkage and selection operator (LASSO) regression model was employed to select the corresponding features. Based on these selected features, logistic regression analysis was used to aid the construction of these three radiomics signatures (GSUS, CEUS and GSCEUS radiomics signature). In addition, 80 patients (IMSPDMDE40 IDC40) were recruited between January 2021 and November 2021 and were used as the validation cohort. The best radiomics signature was selected. Based on the clinical parameters and the radiomics signature, a classification model was built. Finally, the classification model was assessed using nomogram and decision curve analyses. Three radiomics signatures were able to differentiate IMSPDMDE from IDC. The GSCEUS radiomics signature outperformed the other two radiomics signatures and the AUC, sensitivity, specificity, and accuracy were estimated to be 0.876, 0.756, 0.804, and 0.798 in the training cohort and 0.796, 0.675, 0.838 and 0.763 in the validation cohort, respectively. The lower patient age (p<0.001), higher neutrophil count (p<0.001), lack of pausimenia (p0.023) and GSCEUS radiomics features (p<0.001) were independent risk factors of IMSPDMDE. The classification model that included the clinical factors and the GSCEUS radiomics signature outperformed the GSCEUS radiomics signature alone (the AUC values of the training and validation cohorts were 0.962 and 0.891, respectively). The nomogram was applied to the validation cohort, reaching optimal discrimination, with an AUC value of 0.891, a sensitivity of 0.888, and a specificity of 0.750. The present study combined the clinical parameters with the GSCEUS radiomics signature and developed a nomogram. This GSCEUS radiomics-based classification model could be used to differentiate IMSPDMDE from IDC in a non-invasive manner.

Risk of developing depression from endocrine treatment A nationwide cohort study of women administered treatment for breast cancer in South Korea.

Although previous studies demonstrated no association between depression and tamoxifen in patients with breast cancer, there is still a limited amount of long-term follow-up data. This study aimed to evaluate the relationship between endocrine treatment and the risk of depression. This nationwide population-based cohort study used data obtained over a 14-year period (January 2007 to December 2021) from the Korean National Health Insurance claims database. All female patients with breast cancer were included. We examined the incidence of depression in patients who underwent endocrine treatment, and those who did not undergo endocrine treatment constituted the control group. The data from 11,109 patients who underwent endocrine treatment and 6,615 control patients between 2009 and 2010 were analyzed. After performing matching for comorbidities and age, both groups comprised 6,532 patients. The median follow-up were 119.71 months. Before and after matching was performed, the endocrine treatment was not a significant risk factor for developing depression ( Using a real-world population-based cohort, this study demonstrated that there is no evidence that the endocrine treatment increases the risk of depression.

Identification of novel cuproptosis-related lncRNA signatures to predict the prognosis and immune microenvironment of breast cancer patients.

Cuproptosis is a new modality of cell death regulation that is currently considered as a new cancer treatment strategy. Nevertheless, the prognostic predictive value of cuproptosis-related lncRNAs in breast cancer (BC) remains unknown. Using cuproptosis-related lncRNAs, this study aims to predict the immune microenvironment and prognosis of BC patients. and develop new therapeutic strategies that target the disease. The Cancer Genome Atlas (TCGA) database provided the RNA-seq data along with the corresponding clinical and prognostic information. Univariate and multivariate Cox regression analyses were performed to acquire lncRNAs associated with cuproptosis to establish predictive features. The Kaplan-Meier method was used to calculate the overall survival rate (OS) in the high-risk and low-risk groups. High risk and low risk gene sets were enriched to explore functional discrepancies among risk teams. The mutation data were analyzed using the MAFTools r-package. The ties of predictive characteristics and immune status had been explored by single sample gene set enrichment analysis (ssGSEA). Last, the correlation between predictive features and treatment condition in patients with BC was analyzed. Based on prognostic risk models, we assessed associations between risk subgroups and immune scores and immune checkpoints. In addition, drug responses in at-risk populations were predicted. We identified a set of 11 Cuproptosis-Related lncRNAs (GORAB-AS1, AC 079922.2, AL 589765.4, AC 005696.4, Cytor, ZNF 197-AS1, AC 002398.1, AL 451085.3, YTH DF 3-AS1, AC 008771.1, LINC 02446), based on which to construct the risk model. In comparison to the high-risk group, the low-risk patients lived longer (p < 0.001). Moreover, cuproptosis-related lncRNA profiles can independently predict prognosis in BC patients. The AUC values for receiver operating characteristics (ROC) of 1-, 3-, and 5-year risk were 0.849, 0.779, and 0.794, respectively. Patients in the high-risk group had lower OS than those in the low-risk group when they were divided into groups based on various clinicopathological variables. The tumor burden mutations (TMB) correlation analysis showed that high TMB had a worse prognosis than low-TMB, and gene mutations were found to be different in high and low TMB groups, such as PIK3CA (36% versus 32%), SYNE1 (4% versus 6%). Gene enrichment analysis indicated that the differential genes were significantly concentrated in immune-related pathways. The predictive traits were significantly correlated with the immune status of BC patients, according to ssGSEA results. Finally, high-risk patients showed high sensitivity in anti-CD276 immunotherapy and conventional chemotherapeutic drugs such as imatinib, lapatinib, and pazopanib. We successfully constructed of a cuproptosis-related lncRNA signature, which can independently predict the prognosis of BC patients and can be used to estimate OS and clinical treatment outcomes in BRCA patients. It will serve as a foundation for further research into the mechanism of cuproptosis-related lncRNAs in breast cancer, as well as for the development of new markers and therapeutic targets for the disease.

Association of body composition with clinical outcome in Chinese women diagnosed with breast cancer.

This study aims to explore the association of body composition with clinical outcomes in Chinese women diagnosed with breast cancer. A total of 2,948 Chinese female patients with breast cancer have been included in this retrospective study. Body composition mainly includes the measurements of adiposity and muscle mass. Visceral fat area (VFA) is used to measure visceral obesity, while appendicular skeletal muscle mass index (ASMI) is utilized to evaluate sarcopenia. The endpoints of this study are disease-free survival (DFS) and overall survival (OS). The association of the body composition parameters with DFS and OS was statistically analyzed. The median follow-up time for survivors was 42 months (range, 3 to 70 months). In total, 194 patients (6.9%) had breast cancer recurrence, and 32 patients passed away (1.1%). Among the 2,948 patients included, 1,226 (41.6%) patients were viscerally obese, and 511 (17.3%) patients were sarcopenic. We found that visceral obesity had a significant prognostic impact on DFS (HR, 1.46 95% CI, 1.10-1.95 Visceral obesity is associated with a higher risk of disease recurrence, and sarcopenia is significantly associated with increased recurrence and overall mortality among Chinese women with breast cancer. Body composition assessment could be a simple and useful approach in breast cancer management. Further studies can focus on decreasing visceral fat and increasing skeletal muscle mass to improve prognosis in breast cancer survivors.

Noninvasive assessment of breast cancer molecular subtypes on multiparametric MRI using convolutional neural network with transfer learning.

To evaluate the performances of multiparametric MRI-based convolutional neural networks (CNNs) for the preoperative assessment of breast cancer molecular subtypes. A total of 136 patients with 136 pathologically confirmed invasive breast cancers were randomly divided into training, validation, and testing sets in this retrospective study. The CNN models were established based on contrast-enhanced T For the separation of each subtype from other subtypes on the testing set, the T T

LINC00467 an oncogenic long noncoding RNA.

Long non-coding RNAs (lncRNAs) have been found to play essential roles in the cell proliferation, fission and differentiation, involving various processes in humans. Recently, there is more and more interest in exploring the relationship between lncRNAs and tumors. Many latest evidences revealed that LINC00467, an oncogenic lncRNA, is highly expressed in lung cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma, breast cancer, glioblastoma, head and neck squamous cell carcinoma, osteosarcoma, and other malignant tumors. Besides, LINC00467 expression was linked with proliferation, migration, invasion and apoptosis via the regulation of target genes and multiple potential pathways. We reviewed the existing data on the expression, downstream targets, molecular mechanisms, functions, relevant signaling pathways, and clinical implications of LINC00467 in various cancers. LINC00467 may serve as a novel biomarker or therapeutic target for the diagnosis and prognosis of various human tumors.

Comparing outcomes of single-port insufflation endoscopic breast-conserving surgery and conventional open approach for breast cancer.

In the surgical treatment of breast cancer, the goal of surgeons is to continually create and improve minimally invasive surgical techniques to increase patients quality of life. Currently, routine breast-conserving surgery is often performed using two obvious incisions. Here, we compare the clinical efficacy and aesthetic outcomes of a novel technique using one incision, called single-port insufflation endoscopic breast-conserving surgery (SIE-BCS), vs. conventional breast-conserving surgery (C-BCS) in patients with early-stage breast cancer. A total of 180 patients with stage I or stage II breast cancer participated in this study, of whom 63 underwent SIE-BCS and 117 underwent C-BCS. Logistic regression analysis was conducted to assess the risk of local recurrence and metastasis. Aesthetic outcomes were evaluated using the BREAST-Q scale. The mean operation time was significantly longer for SIE-BCS (194.9 ± 71.5 min) than for C-BCS (140.3 ± 56.9 min), but the mean incision length was significantly shorter for SIE-BCS than for C-BCS (3.4 ± 1.2 cm vs. 8.6 ± 2.3 cm). While both surgeries yielded similar BREAST-Q ratings for satisfaction with breasts and sexual well-being, SIE-BCS was associated with significantly better ratings for physical well-being (chest area) and psychological well-being. Additionally, SIE-BCS was associated with decreased rates of adverse effects of radiation. The preliminary analysis showed that SIE-BCS did not increase the risk of local recurrence or metastasis. The novel single-port insufflation endoscopic assisted BCS technique is feasible, safe, and improves patients postoperative comfort and psychological well-being, as compared to the conventional technique.

Circulating levels of PCSK9, ANGPTL3 and Lp(a) in stage III breast cancers.

Cholesterol and lipids play an important role in sustaining tumor growth and metastasis in a large variety of cancers. ANGPTL3 and PCSK9 modify circulating cholesterol levels, thus availability of lipids to peripheral cells. Little is known on the role, if any, of circulating lipid-related factors such as PCSK9, ANGPTL3 and lipoprotein (a) in cancers. To compare circulating levels of PCSK9, ANGPTL3, and Lp(a) in women with stage III breast cancer versus women with premalignant or benign breast lesions. Twenty-three plasma samples from women diagnosed with a stage III breast cancer (ductal, lobular or mixed) were matched for age with twenty-three plasma samples from women bearing premalignant (stage 0, n 9) or benign (n 14) breast lesions. The lipid profile (Apo B, total cholesterol, HDL cholesterol and triglycerides levels) and Lp(a) were measured on a Roche Modular analytical platform, whereas LDL levels were calculated with the Friedewald formula. ANGPTL3 and PCSK9 plasma levels were quantitated by ELISA. All statistical analyses were performed using SAS software version 9.4. PCSK9 levels were significantly higher in women with stage III breast cancer compared to age-matched counterparts presenting a benign lesion (95.9 ± 27.1 ngmL vs. 78.5 ± 19.3 ngmL, p < 0.05, n 14). Moreover, PCSK9 levels positively correlated with breast disease severity (benign, stage 0, stage III) (Rho 0.34, p < 0.05, n 46). In contrast, ANGPTL3 and Lp(a) plasma levels did not display any association with breast disease status and lipids did not correlate with disease severity. In this small cohort of 46 women, PCSK9 levels tended to increase with the severity of the breast disease. Given that PCSK9 plays an important role in maintaining cholesterolemia, and a potential role in tumor evasion, present results warrant further investigation into a possible association between PCSK9 levels and breast cancer severity in larger cohorts of women.

Immediate Prosthesis Breast Reconstruction A Comparison Between Ambulatory Surgery Versus Traditional Hospitalization Based on the Propensity Score Matching Method.

The positive benefits of immediate prosthesis breast reconstruction (IPBR) are incontrovertible. During the COVID-19 pandemic, health care resources became scarce. The implementation of outpatient immediate prosthesis breast reconstruction (OIPBR) can improve the efficiency of medical care and reduce viral exposure. Very few studies have focused on OIPBR and this study aimed to fill this gap by evaluating outcomes of OIPBR compared with traditional hospitalization IPBR (THIPBR) in terms of complications and quality of life. The study enrolled patients undergoing IPBR at Tianjin Medical University Cancer Institute and Hospital between January 1, 2020, and September 30, 2021. Outcomes were defined as postoperative complications and quality of life before reconstruction and at 3-month follow-up. Quality of life was assessed by BREAST-Q questionnaire. Inverse probability of treatment weighting and propensity score matching (PSM) were applied to adjust for confounders. A total of 135 patients were enrolled, including 110 with THIPBR and 25 with OIPBR. After matching, baseline characteristics were well balanced. Patients with OIPBR had lower rates of lymphedema on the surgery side (p 0.041) and readmission (p 0.040) than patients with THIPBR. No statistically significant differences in the quality of life metrics of psychosocial well-being, sexual well-being, satisfaction with breast and physical well-being of the chest were found between the two groups. OIPBR is a safe and efficient alternative to THIBPR during the COVID-19 pandemic. It is recommended when medical conditions allow to conserve medical resources. Accelerated technical training for the performance of OIPBR at the hospital level should be expedited. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com00266 .

Copy number variants as modifiers of breast cancer risk for BRCA1BRCA2 pathogenic variant carriers.

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) 1.21), 95% confidence interval (95% CI 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.

Effects of Systemic Lidocaine Versus Dexmedetomidine on the Recovery Quality and Analgesia After Thyroid Cancer Surgery A Randomized Controlled Trial.

Surgical management is commonly used for thyroid cancer. We evaluated the effects of systemic lidocaine versus dexmedetomidine on the recovery quality and analgesia after thyroid cancer surgery. A total of 120 patients with thyroid cancer were randomly allocated to group L (received lidocaine 1.5 mgkg loading, continuously infused 1.5 mgkg per hour), group D (received dexmedetomidine 0.5 µgkg loading, continuously infused 0.5 µgkg per hour) and group C (received normal saline), with 40 cases in each group. Anaesthesia induction and maintenance were performed using target-controlled infusions (TCIs) of propofol and remifentanil. The primary outcome of the quality of recovery-15 (QoR-15) score was recorded on the day before surgery and postoperative day 1 (POD1). Secondary outcomes included the consumption of remifentanil during surgery, time to first required rescue analgesia, number of patients requiring rescue analgesia, postoperative cumulative consumption of tramadol, visual analogue scale (VAS) pain score, incidence of postoperative nausea or vomiting (PONV) and side effects. The total score of the QoR-15 at POD1 (median, IQR) was higher in group L (128.0, 122.0-132.8) and group D (127.5, 122.5-132.5) compared to group C (118.5, 113.0-123.5) (P 0.000). Compared to group C, systemic lidocaine and dexmedetomidine reduced cumulative consumption of remifentanil and VAS pain score (P 0.000). The time to first required rescue analgesia (mean, SD) was longer in group L (8.1 h, 1.2 h) and group D (8.5 h, 1.9 h) than group C (5.9 h, 0.9 h) (P 0.000). The number of patients requiring rescue analgesia was lower in group L (840, 20%) and group D (640, 15%) than group C (1640, 40%) (P 0.029), and cumulative consumption of tramadol (mean, SD) was lower in group L (44.0 mg, 17.1 mg) and group D (51.7 mg, 14.1 mg) than group C (73.9 mg, 18.4 mg) (P 0.000). The incidence of PONV in group L (740, 17.5%) and group D (940, 22.5%) was lower than group C (1840, 45.0%) (P 0.016). Bradycardia (heart rate less than 50 beatsmin or lower) was noted in 25 patients (2540, 62.5%), which was reversed by intravenous administration of atropine 0.5 mg. Systemic lidocaine and dexmedetomidine had similar effects on enhancing the quality of recovery, alleviating the intensity of pain and reducing the incidence of PONV after thyroid cancer surgery. However, dexmedetomidine may result in bradycardia. Therefore, lidocaine was superior to dexmedetomidine. ChiCTR.org.cn (ChiCTR2000038442). Registered on September 22, 2020.

High-plex imaging of RNA and proteins at subcellular resolution in fixed tissue by spatial molecular imaging.

Resolving the spatial distribution of RNA and protein in tissues at subcellular resolution is a challenge in the field of spatial biology. We describe spatial molecular imaging, a system that measures RNAs and proteins in intact biological samples at subcellular resolution by performing multiple cycles of nucleic acid hybridization of fluorescent molecular barcodes. We demonstrate that spatial molecular imaging has high sensitivity (one or two copies per cell) and very low error rate (0.0092 false calls per cell) and background (0.04 counts per cell). The imaging system generates three-dimensional, super-resolution localization of analytes at 2 million cells per sample. Cell segmentation is morphology based using antibodies, compatible with formalin-fixed, paraffin-embedded samples. We measured multiomic data (980 RNAs and 108 proteins) at subcellular resolution in formalin-fixed, paraffin-embedded tissues (nonsmall cell lung and breast cancer) and identified >18 distinct cell types, ten unique tumor microenvironments and 100 pairwise ligand-receptor interactions. Data on >800,000 single cells and 260 million transcripts can be accessed at httpnanostring.comCosMx-dataset .

The role of stereotactic radiosurgery in the multidisciplinary management of pituitary metastases.

This study evaluates the role and outcomes of Gamma Knife radiosurgery (GKRS) in the management of pituitary metastases. The records of brain metastases patients who underwent GKRS at the University of Pittsburgh Medical Center during the 10-year interval of 2010-2020 were systematically reviewed. Outcome measures included patient survival, tumor control rate, pituitary hormonal outcomes, visual outcomes, adverse radiation effects (AREs), and need for adjuvant therapy. Eighteen patients with pituitary metastases (eight male median age of 65.5 years) had sufficient clinical follow-up for analysis. The most common primary cancers were non-small cell lung cancer (n 6) and breast cancer (n 4). Patients presented with headache (n 9) and visual difficulties (n 6). One patient underwent resection before GKRS. The median tumor volume was 0.78 cc (range 0.04-6.42 cc). The median overall survival after GKRS was 6.5 months (range 0.5-58 months). The overall survival after GKRS at 3-, 6-, and 12-months were 72.2%, 50.0% and 38.9%, respectively. The tumor control rate was 94.4%. One patient had further progression that required additional GKRS. None of the patients developed AREs after GKRS. GKRS is an effective treatment modality for the multidisciplinary management of patients with pituitary metastases. This minimally-invasive strategy is associated with optimal tumor control rate and low risk to adjacent optic nerves or neurovascular structures.

Synthesis and anticancer activity of new benzensulfonamides incorporating s-triazines as cyclic linkers for inhibition of carbonic anhydrase IX.

Limited presence of hCA IX in normal physiological tissues and their overexpression only in solid hypoxic tumors made this isoform excellent possible target for developing new anticancer agents. We reported designing and synthesis of two novel series of benzenesulfonamides derivatives as hCA IX inhibitors bearing rigid cyclic linkers (1,3,5-dihydrotriazine in series A and 1,3,5-triazine in series B) in replace of traditional linear linkers. Also, novel cyanoethenyl spacer was assembled next to the 1,3,5-triazine linker in series B. Target compounds of series (A) and (B) were screened against four hCA isoforms. Human CA IX efficiently inhibited in series (A) by compound 5a (K

Imaging features and biopsy yield of soft tissue metastatic lesions 10-year single tertiary center experience.

To evaluate imaging features of soft tissue metastases, technical factors associated with diagnostic yield of image-guided biopsy, and clinical impact of biopsy results on patient outcomes. A total of 1605 image-guided soft tissue biopsies were retrospectively identified from December 2010 to December 2020. Included lesions were histologically proven musculoskeletal soft tissue metastases. Lesions were excluded if intraabdominal, intrathoracic, retroperitoneal, associated with osseous lesions or surgical scar implants or arising from skin or lymph nodes. Image guidance modality, needle size, number of cores, and lesion location, size, and depth from skin were recorded. Patient demographics, malignancy history, biopsy-driven changes in management, and survival rate after biopsy were collected. Forty-six patients met the inclusion criteria with a biopsy diagnostic yield of 4446 (95.7%). Metastases were most commonly located truncal (82.6%, p < 0.001) and intramuscular (78.3%, p < 0.001). A total of 3746 (80.4%) biopsies were US-guided. And 946 (19.6%) were CT-guided. There was no significant difference in the number of cores or mean needle gauge between diagnostic and nondiagnostic biopsies. At time of review, 23 (50%) patients were deceased, with a mean survival of 13.5 months after biopsy. The majority (71.7%) of patients had a known primary malignancy at time of biopsy, most commonly lung (24.2%) and breast (24.2%). Overall survival showed no association with anatomic location (p > 0.83) or tissue type (p > 0.34). The most common biopsy-driven outcome was initiation of chemotherapy, immunotherapy, andor radiotherapy (52.2%). Image-guided biopsy for soft tissue metastases has high diagnostic yield and commonly influences clinical management. Metastases were most commonly intramuscular in the trunk and are associated with poor prognosis.

A multi-omics-based investigation of the prognostic and immunological impact of necroptosis-related mRNA in patients with cervical squamous carcinoma and adenocarcinoma.

Necroptosis is a kind of programmed necrosis mode that plays a double-edged role in tumor progression. However, the role of necroptosis-related Messenger RNA (mRNA) in predicting the prognosis and immune response of cervical squamous carcinoma and adenocarcinoma (CESC) has not been fully studied. Firstly, the incidence of somatic mutation rate and copy number variation for 74 necroptosis-related mRNAs (NRmRNAs) were analyzed. Secondly, CESC patients were divided into four stable clusters based on the consensus clustering results and analyzed for correlations with a series of clinical factors. Subsequently, a total of 291 The Cancer Genome Atlas samples were randomly divided into either training or validation cohorts. A Cox proportional hazard model consisting of three NRmRNAs (CXCL8, CLEC9A, and TAB2) was constructed by univariate, least absolute shrinkage and selection operator and multivariate COX regression analysis to identify the prognosis and immune response. Its performance and stability were further validated in another testing dataset (GSE44001) from Gene Expression Omnibus database. The results of the receiver operating characteristic curve, principal component analysis, t-SNE, and nomogram indicated that the prognostic model we constructed can serve as an independent prognostic factor. The combination of the prognostic model and the classic TNM staging system could improve the performance in predicting the survival of CESC patients. In addition, differentially expressed genes from high and low-risk patients are screened by R software for functional analysis and pathway enrichment analysis. Besides, single-sample gene set enrichment analysis revealed that tumor-killing immune cells were reduced in the high-risk group. Moreover, patients in the low-risk group are more likely to benefit from immune checkpoint inhibitors. The analysis of tumor immune dysfunction and exclusion scores, M6A-related genes, stem cell correlation and Tumor mutational burden data with clinical information has quantified the expression levels of NRmRNAs between the two risk subgroups. According to tumor immune microenvironment scores, Spearmans correlation analysis, and drug sensitivity, immunotherapy may have a higher response rate and better efficacy in patients of the low-risk subgroup. In conclusion, we have reported the clinical significance of NRmRNAs for the prognosis and immune response in CESC patients for the first time. Screening of accurate and effective prognostic markers is important for designing a multi-combined targeted therapeutic strategy and the development of individualized precision medicine.

Breast microecology improvement using probiotics following needle aspiration in patients with lactational breast abscess a multi-center randomized double-blind controlled trial.

Although oral probiotics can improve breast microecology and alleviate the inflammatory response, there are no data regarding cases with existing abscesses. We aimed to investigate the effect of Lactobacillus fermentum CECT5716 during needle aspiration in patients with lactational breast abscesses. Patients (aged 20-41 years) with lactational single-cavity breast abscesses (diameter 3-6 cm) from 12 hospitals were randomly assigned to the experimental (n 51) and control groups (n 50). Outcome measures included the abscess cure rate on treatment day-5, delactation rate, relieving pain rate, and number of needle aspirations until day-28. The experimental groups 5-day cure rate (43.1%) was significantly higher (p < 0.05). Breastfeeding continuation on day-5 did not differ significantly (experimental group 88.2%, control group 96.0%, p 0.269). In the experimental and control groups, 19.6% and 14.0% of patients experienced moderate to severe pain on day-5, respectively, with no statistically significant differences (p 0.451). Four patients in each group developed diarrhea, with adverse reaction rates of 7.84% and 8.0%, respectively. No adverse reactions were reported in the infants. L. fermentum can shorten the healing time in patients with lactational breast abscesses.Trial registration This study was registered in the Chinese Clinical Trial Registry ( httpwww.chictr.org.cn ), registration number ChiCTR2000032682, registration date 6May 2020 first entry date 11May2020.

METTL3LINC00662miR-186-5p feedback loop regulates docetaxel resistance in triple negative breast cancer.

Insight into the mechanism of docetaxel resistance in breast cancer may help to improve prognosis. We aimed to investigate the role of N6-methyladenosine (m6A) and the METTL3LINC00662miR-186-5p pathway in regulating docetaxel resistance in triple negative breast cancer (TNBC). We have recruited 193 pathologically diagnosed TNBC patients from 2016 to 2017 in our hospital. Quantitative real-time PCR was used to evaluate the expression of LINC00662 and miR-186-5p both in vivo and in vitro. CCK8 tests were used to assess cell viability. ELISA was used for protein expression evaluation. Dual luciferase reporter gene assay and RNA pull-down were used to evaluate the interaction between LINC00662 and miR-186-5p. m6A levels were enhanced in breast cancer tissues and cells. LINC00662, miR-186-5p and METTL3 were differentially expressed in vivo, and METTL3 expression was associated with LINC00662 and miR-186-5p expression. LINC00662 and miR-186-5p were differentially expressed in vitro LINC00662 promoted cell viability and decreased the apoptosis rate, whereas miR-186-5p inhibited cell viability and increased the apoptosis rate. Furthermore, we found that METTL3 regulated m6A levels in docetaxel-resistant breast cancer cells by regulating the expression of LINC00662. Moreover, LINC00662 and miR-186-5p regulated the cell viability rate of docetaxel-resistant breast cancer cells. Further experiments showed that LINC00662 directly interacted with miR-186-5p to exert biological functions besides miR-186-5p could regulate the expression of METTL3. METTL3 promotes m6A levels and docetaxel resistance in breast cancer by regulating the expression of LINC00662 and miR-186-5p more experiments are needed to clarify the role of m6A regulation in drug resistance.

An interpretable semi-supervised framework for patch-based classification of breast cancer.

Developing effective invasive Ductal Carcinoma (IDC) detection methods remains a challenging problem for breast cancer diagnosis. Recently, there has been notable success in utilizing deep neural networks in various application domains however, it is well-known that deep neural networks require a large amount of labelled training data to achieve high accuracy. Such amounts of manually labelled data are time-consuming and expensive, especially when domain expertise is required. To this end, we present a novel semi-supervised learning framework for IDC detection using small amounts of labelled training examples to take advantage of cheap available unlabeled data. To gain trust in the prediction of the framework, we explain the prediction globally. Our proposed framework consists of five main stages data augmentation, feature selection, dividing co-training data labelling, deep neural network modelling, and the interpretability of neural network prediction. The data cohort used in this study contains digitized BCa histopathology slides from 162 women with IDC at the Hospital of the University of Pennsylvania and the Cancer Institute of New Jersey. To evaluate the effectiveness of the deep neural network model used by the proposed approach, we compare it to different state-of-the-art network architectures AlexNet and a shallow VGG network trained only on the labelled data. The results show that the deep neural network used in our proposed approach outperforms the state-of-the-art techniques achieving balanced accuracy of 0.73 and F-measure of 0.843. In addition, we compare the performance of the proposed semi-supervised approach to state-of-the-art semi-supervised DCGAN technique and self-learning technique. The experimental evaluation shows that our framework outperforms both semi-supervised techniques and detects IDC with an accuracy of 85.75%, a balanced accuracy of 0.865, and an F-measure of 0.773 using only 10% labelled instances from the training dataset while the rest of the training dataset is treated as unlabeled.

Surgical complications in immediate and delayed breast reconstruction A systematic review and meta-analysis.

Because of improved aesthetic results, immediate breast reconstruction has become the most widely used timing of reconstruction following mastectomy. Many studies report complication rates between immediate and delayed reconstructions at certain medical institutions, but no systematic reviews exist to summarize the literature. This systematic review was conducted to assess the outcomes in women who underwent immediate versus delayed breast reconstruction following mastectomy for breast cancer. Cochrane, PubMed, and EMBASE electronic databases were screened, and data were extracted from included studies. The clinical outcomes assessed were surgical complications, length of postoperative hospital stay, and reoperation rate. A total of 30 studies met the inclusion criteria for the review and provided enough data to be included in the meta-analysis (14,034 patients). Women receiving immediate breast reconstruction were significantly more likely to experience surgical complications (OR 1.30, 95% CI 1.03, 1.65 p 0.03). Sensitivity analysis showed that women receiving immediate reconstruction were also more likely to experience infection (OR 1.41, 95% 1.04, 1.92 p 0.03) and hematomaseroma (OR 2.01, 95% CI 1.27-3.17 p 0.003). Furthermore, a separate sensitivity analysis showed no significant differences in reported outcomes when comparing studies whose patient cohorts received post-mastectomy radiation therapy (PMRT). This study provides evidence that immediate breast reconstruction generally increases the risk of complications in comparison with delayed reconstruction. Additional prospective and observational studies are needed to determine the role of PMRT and reconstruction surgical technique in the incidence of complications between immediate and delayed reconstructions.

DGANet A Dual Global Attention Neural Network for Breast Lesion Detection in Ultrasound Images.

Deep learning-based breast lesion detection in ultrasound images has demonstrated great potential to provide objective suggestions for radiologists and improve their accuracy in diagnosing breast diseases. However, the lack of an effective feature enhancement approach limits the performance of deep learning models. Therefore, in this study, we propose a novel dual global attention neural network (DGANet) to improve the accuracy of breast lesion detection in ultrasound images. Specifically, we designed a bilateral spatial attention module and a global channel attention module to enhance features in spatial and channel dimensions, respectively. The bilateral spatial attention module enhances features by capturing supporting information in regions neighboring breast lesions and reducing integration of noise signal. The global channel attention module enhances features of important channels by weighted calculation, where the weights are decided by the learned interdependencies among all channels. To verify the performance of the DGANet, we conduct breast lesion detection experiments on our collected data set of 7040 ultrasound images and a public data set of breast ultrasound images. YOLOv3, RetinaNet, Faster R-CNN, YOLOv5, and YOLOX are used as comparison models. The results indicate that DGANet outperforms the comparison methods by 0.2%-5.9% in total mean average precision.

Breast MRI assists in decision-making for surgical excision of atypical ductal hyperplasia.

Atypical ductal hyperplasia diagnosed on percutaneous breast biopsy typically undergoes surgical excision, upgrading to invasive breast cancer or ductal carcinoma in situ in 10% to 53%. In efforts to limit excision to those with highest upgrade risk, we sought to determine if breast magnetic resonance imaging has value in predicting upgrade. In this study, we will describe magnetic resonance imaging presentation of atypical ductal hyperplasia and assess magnetic resonance imaging accuracy in predicting upgrade. All female patients ≥18 years with atypical ductal hyperplasia on percutaneous breast biopsy undergoing magnetic resonance imaging from 2008 to 2020 were included. Patient demographics, imaging presentation, magnetic resonance imaging enhancement kinetic curves, and pathology features were captured. Categorical variables were analyzed using Fisher exact to test for association between variables and upgrade. Continuous variables were analyzed using t tests. Magnetic resonance imaging was performed for 125 percutaneous breast biopsy with atypical ductal hyperplasia 67 after and 58 before atypical ductal hyperplasia diagnosis. On magnetic resonance imaging, atypical ductal hyperplasia site had no enhancement in 45 (36%), nonmass enhancement in 50 (40%), and mass enhancement in 30 (24%). In total, 28% had atypical ductal hyperplasia diagnosed by magnetic resonance imaging-guided percutaneous breast biopsy. Surgical excision was performed for 96 (76.8%) and 15 (15.6%) upgraded (11 ductal carcinoma in situ, 4 invasive breast cancer). All 15 upgrades had enhancement. Any kinetic pattern enhancement was significantly associated with upgrade (P .009) with upgrade most strongly associated with type III washout. The lowest risk for upgrade was pure atypical ductal hyperplasia and no magnetic resonance imaging enhancement (0%, n 25). Active monitoring may be safely offered to women with pure atypical ductal hyperplasia on percutaneous breast biopsy when magnetic resonance imaging shows no enhancement. Any enhancement at atypical ductal hyperplasia site, particularly type III washout kinetics, should continue to undergo excision.

Thyroid hormone replacement following lobectomy Long-term institutional analysis 15 years after surgery.

The decision to pursue lobectomy versus total thyroidectomy is highly individualized. The rate of thyroid hormone replacement therapy after lobectomy varies considerably (15%-48%) and studies are limited by short-term follow-up. We sought to assess long-term thyroid hormone replacement therapy-requirement for lobectomy. Patients undergoing lobectomy from January 2005 to July 2010 at an academic institution were reviewed. Demographic, laboratory, pathology, and thyroid hormone replacement therapy use were compared. In total, 235 patients were included. The rate of thyroid hormone replacement therapy after lobectomy was 46.8% (110235). The majority were female (84.7%), with a mean age of 52 ± 1 years, 97% with benign pathology, and the median duration of follow-up was 7.2 years. Among the 110 thyroid hormone replacement therapy, the mean postoperative thyroid stimulating hormone level 9.08 ± 0.96m IUL and the time to thyroid hormone replacement therapy-initiation was 621 days 24% started therapy ≥2 years after surgery. There was no difference in age, sex, or malignancy. Hashimoto thyroiditis was diagnosed in 21.8% patients who underwent thyroid hormone replacement therapy versus 8.0% of those without thyroid hormone replacement therapy (odds ratio 3.2 95% confidence interval, 1.43-6.79 P < .001). On multivariate analysis, only Hashimoto thyroiditis was independently associated with thyroid hormone replacement therapy use (odds ratio 2.88 95% confidence interval, 1.3-6.6 P .012). With long-term follow-up, nearly 50% of patients who underwent lobectomy for benign disease required thyroid hormone replacement therapy and nearly one-quarter of these patients not starting until ≥2 years after surgery. Therefore, patients who undergo thyroid lobectomy should be counseled appropriately and thyroid function followed for a minimum of 2 years.

Impact of chemotherapy during pregnancy on fetal growth.

Chemotherapy crosses the placenta, however, it remains unclear to what extent it affects fetal growth. The current literature suggests up to 21% of the offspring of women receiving chemotherapy are small for gestational age (SGA, birth weight <10th percentile). Limiting research to birth weights only might misjudge fetal growth restriction (FGR) in this high-risk population with multiple risk factors for impaired fetal growth. Moreover, the role of the duration of chemotherapy and gestational age at initiation of chemotherapy in fetal growth is yet poorly understood. This retrospective cohort study evaluates fetal growth and neonatal birthweights in pregnant women receiving chemotherapy. All pregnant patients, registered by the International Network of Cancer, Infertility and Pregnancy (INCIP), treated with chemotherapy with at least two ultrasounds reporting on fetal growth, were eligible for this study. Duration and gestational age at initiation of chemotherapy were our major determinants, followed by cancer type and stage, maternal characteristics (parity, BMI, ethnicity hypertension, and diabetes) and individual cytotoxic agents (anthracycline, taxanes, and platinum). Fetal growth outcomes were described using the following mutually exclusive groups (1) FGR, based on a Delphi consensus (2016) (2) low risk SGA (birth weight below the 10th percentile), but an estimated growth above the 10th percentile (3) fetal growth disturbance, which did not meet all FGR criteria (4) non-FGR. Obstetric and oncological characteristics were compared between the growth impaired groups and non-FGR group. We calculated estimated fetal weight (EFW) according to Hadlocks formula (1991) and birth weight percentile according to Nicolaides (2018). We used univariable and multivariable regression, and linear mixed effect models to investigate the effect of duration and gestational age at initiation of chemotherapy on birth weight, and fetal growth, respectively. We included 201 patients, diagnosed with cancer between March 2000 and March 2020. Most patients were diagnosed with breast cancer ( This study demonstrates that FGR is common after chemotherapy in pregnancy, and that the duration of chemotherapy has a negative impact. Sonographic follow-up of fetal growth and well-being is recommended.

Synchrotron Fourier-Transform Infrared Microspectroscopy Characterization of in vitro polarized tumor-associated macrophages stimulated by the secretome of inflammatory and non-inflammatory breast cancer cells.

Studies suggested that the pathogenesis of inflammatory breast cancer (IBC) is related to inflammatory manifestations accompanied by specific cellular and molecular mechanisms in the IBC tumor microenvironment (TME). IBC is characterized by significantly higher infiltration of tumor-associated macrophages (TAMs) that contribute to its metastatic process via secreting many cytokines such as TNF, IL-6, IL-8, and IL-10 that enhance invasion and angiogenesis. Thus, there is a need to first understand how IBC-TME modulates the polarization of TAMs to better understand the role of TAMs in IBC. Herein, we used gene expression signature and Synchrotron Fourier-Transform Infrared Microspectroscopy (SR-μFTIR) to study the molecular and biochemical changes, respectively of in vitro polarized TAMs stimulated by the secretome of IBC and non-IBC cells. The gene expression signature showed significant differences in the macrophages polarization-related genes between stimulated TAMs. FTIR spectra showed absorption bands in the region of 1700-1500 cm

Shoulder Kinematics of Axillary Web Syndrome in Women Treated for Breast Cancer.

To better understand how the shoulder moves in breast cancer survivors with axillary web syndrome (AWS), we compared 3-dimensional (3D) shoulder kinematics during shoulder elevation among breast cancer survivors with and without AWS 5 years postoperatively. Although research consistently shows decreased shoulder range of motion with AWS, we do not understand the underlying biomechanics. Nested case control study. University Academic Breast Center. Twenty-five women who had surgery 5 years previously for unilateral breast cancer with the removal of at least 1 lymph node participated in this study (N25). Twelve participants had AWS 13 women did not have AWS. Not applicable. Three-dimensional shoulder kinematic data during shoulder forward flexion, scapular plane abduction, and coronal plane abduction were collected using 3D electromagnetic motion tracking. Kinematic data were extracted at 30°, 60°, 90°, and 120° of arm elevation for scapular upward rotation, internal rotation, and posterior tilt as well as for glenohumeral external rotation. Women with AWS demonstrated 15.2° less scapular upward rotation at 120° humerothoracic elevation (95% confidence interval -25.2, -5.2, P.005), regardless of plane. No significant between-group differences were found for any other angle of scapular upward rotation, nor for scapular internal rotation, scapular posterior tilt, or glenohumeral axial rotation at any angle. Five years after surgery for breast cancer, women diagnosed with AWS have altered scapulohumeral kinematics that may place them at an increased risk of shoulder pain based on existing kinematic literature in healthy cohorts. This information can help guide rehabilitation programs for breast cancer survivors to facilitate pain-free upper extremity function after treatment.

Hypoxia promotes the expression of Von Willebrand factor in breast cancer cells by up-regulating the transcription factor YY1 and down-regulating the hsa-miR-424.

Von Willebrand factor (VWF), a large glycoprotein with hemostatic properties, is mainly synthesized by megakaryocytes and endothelial cells (ECs). In recent years, studies have found that tumor cells also can produce VWF de novo. Tumor growth is usually accompanied by hypoxic environment, and whether hypoxia will influence von Willebrand factor production in tumor cells is still unknown. In this research, we demonstrated that hypoxia could induce the production of VWF in breast cancer cells (MCF-7 and MDA-MB-231 cell lines), and promoted cell migration as well as angiogenesis. Notably, VWF is a key factor for hypoxia to promote breast cancer cell migration and angiogenesis, and knocking down VWF can attenuate the effects of hypoxia. Further study was conducted on the molecular mechanism to clarify why hypoxia can promote VWF synthesis in breast cancer cells. We found that Yin-Yang 1 (YY1, a transcription factor) had a binding site to the promoter region of VWF, and acted as a transcriptional activator of VWF. Meanwhile, hsa-miR-424 inhibited VWF production by associating with the 3-UTR of VWF mRNA. Here, we proved that hypoxia up-regulated the transcription factor YY1 and down-regulated hsa-miR-424 to increase the expression level of VWF. Additionally, knockdown of transcription factor YY1 and transfection of hsa-miR-424 mimics had a synergistic effect in reducing hypoxia-induced VWF production of breast cancer cells, cell migration and angiogenesis in vitro.

Non-coding RNAs in breast cancer Implications for programmed cell death.

Cell death is a necessary event in life and is crucial for the regulation of organismal development, homeostasis, aging and pathological conditions. There are different modes of cell death, i.e., regulated and nonregulated. Cell death induced by programmed cell death (PCD) has gained increasing attention in recent years. Abnormal control of PCD plays an important role in tumorigenesis. For example, tumor cells are relatively resistant to apoptosis, and the induction of cell death is also an important mechanism underlying the antitumor effects of current clinical chemotherapeutic agents. Recently, studies have revealed that noncoding RNAs (ncRNAs) are involved in regulating multiple biological processes of breast cancer, including PCD. NcRNAs can exert both protumorigenic and antitumorigenic effects, depending on their expression patterns. Therefore, constructing ncRNA-based therapies to target PCD may be a promising therapeutic strategy for breast cancer. Herein, this review discusses the function of various ncRNAs in regulating the PCD of breast cancer cells. In addition, given the recent trend of utilizing ncRNAs as cancer therapeutics, we also discuss the great potential applications of ncRNAs as biomarkers or activators of PCD in breast cancer.

Multiple Bayesian network meta-analyses to establish therapeutic algorithms for metastatic triple negative breast cancer.

Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 sfurther-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel ± bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA12-mutant patients, and immunotherapy chemotherapy in PD-L1-positive mTNBC, performed similar to paclitaxel ± bevacizumab. In PD-L1-positive mTNBC, pembrolizumab chemotherapy was better than atezolizumab nab-paclitaxel in terms of OS according to SUCRA values. In secondfurther-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA12-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, according to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS).

Sessile droplet array for sensitive profiling of multiple extracellular vesicle immuno-subtypes.

The sensitive detection of the multiple immuno-subtypes of cancer-specific extracellular vesicles (EVs) has emerged as a promising method for multiclass cancer diagnosis however, its limitations in sensitivity, accessibility, and multiple detection of EV subtypes have hindered its further implementation. Here, we present a platform for sensitive EV detection enabled by sessile droplet array (eSD) that exploits enhanced immuno-capture of EVs via evaporation-driven radial flows in a sessile droplet. Compared to a micro-well without internal flows, this platform demonstrates significantly enhanced EV capture and detection by detecting low levels of EVs with a detection limit of 384.7 EVs per microliter, which is undetectable in the micro-well. In addition, using a small sample consumption of ∼0.2 μL plasma per droplet, the platform detects EV immuno-subtypes against seven different antibodies in patient plasma samples of different cancer types (liver, colon, lung, breast and prostate cancers). Further, using the profiling data, the platform exhibits a sensitivity of 100% (95% confidence interval (CI) 83-100%) and a specificity of 100% (95% CI 40-100%) for the diagnosis of cancer, and classified cancer types with an overall accuracy of 96% (95% CI 86-100%) using a two-staged algorithm based on quadratic discriminant analysis technique for machine learning.

Enhancing anti-tumor effect of ultrasensitive bimetallic RuCu nanoparticles as radiosensitizers with dual enzyme-like activities.

Radiotherapy (RT), through the generation of reactive oxygen species (ROS) and DNA damage to tumor cells caused by high-energy irradiation, has been a widely applied cancer treatment strategy in clinic. However, the therapeutic effect of traditional RT is restricted by the insufficient radiation energy deposition and the side effects on normal tissues. Recently, multifunctional nano-formulations and synergistic therapy has been developed as attractive strategies for used to enhancing the efficacy and safety of RT. Herein, we show that a bimetallic nanozyme (copper-modified ruthenium nanoparticles, RuCu NPs), containing the high atomic number (Z) element Ru as a novel radiosensitizer, offers an ideal solution to RT sensitization, with ultrasensitive peroxidase (POD)-like activity and catalase (CAT)-like activity. Density functional theory (DFT) calculations also clarified the optimal POD-like catalytic ratio of RuCu NPs and further revealed the mechanism of its supper catalytic activity. Under X-ray exposure, RuCu NPs coated with poly(ethylene glycol) (PEG) exhibited simultaneously improved the ROS production and relieved tumor hypoxia in the acid tumor microenvironment (TME), and demonstrated remarkable therapeutic efficacy in the MDA-MB-231 breast cancer model. Our results provide a proof-of-concept for a RT sensitization strategy, which combine the intrinsic nature of high-Z element and the advantages of nanozymes to overcome the tricky drawbacks existed in radiotherapy, and further open a new direction of exploring novel nanozyme-based strategies for tumor catalytic therapy and synergistic radiotherapy.

Multifunctional light-activatable nanocomplex conducting temperate-heat photothermal therapy to avert excessive inflammation and trigger augmented immunotherapy.

Photothermal therapy (PTT) has been known as an effective weapon against cancer. However, the necrosis induced by hyperthermia post PTT can trigger excessive inflammation response and arouse tumor self-protection resulting in tumor immunosuppression, metastasis and recurrence. To settle this issue, we here reported a multifunctional light-activatable nanocomplex (MILAN) to avoid hyperthermia and achieve temperate-heat PTT for extensive apoptosis, but not necrosis, and further antitumor immune response augmentation to inhibit metastasis and recurrence. Upon NIR irradiation, MILAN would controllably maintain around 43 °C, thus evoking the temperature-triggered phase transformation for the controllable drug release. Then, the released gambogic acid broke the thermoresistance of tumor cells, realizing enhanced apoptosis. Thereafter, the generated tumor-associated antigen accompanied with MILAN could facilitate dendritic cells (DCs) maturation for improved antigen presentation. Furthermore, MILAN promoted the tumor perfusion of DCs and T lymphocytes in triple-negative breast cancer (TNBC) models. Simultaneously, the immunosuppressive microenvironment was relieved and a strong systemic immune response was elicited against tumor progress through MILAN. Consequently, systemic immunity and persistent immune memory effect were fortified for pronounced cancer metastasis and recurrence inhibition. This work tactfully avoids the side effects of hyperthermia and brought a novel insight into cancer immunotherapy against TNBC.

Predicting hormone receptors and PAM50 subtypes of breast cancer from multi-scale lesion images of DCE-MRI with transfer learning technique.

The recent development of artificial intelligence (AI) technologies coupled with medical imaging data has gained considerable attention, and offers a non-invasive approach for cancer diagnosis and prognosis. In this context, improved breast cancer (BC) molecular characteristics assessment models are foreseen to enable personalized strategies with better clinical outcomes compared to existing screening strategies. And it is a promising approach to developing models for hormone receptors (HR) and subtypes of BC patients from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data. In this institutional review board-approved study, 174 BC patients with both DCE-MRI and RNA-seq data in the local database were analyzed. Slice images from tumor lesions and multi-scale peri-tumor regions were used as model inputs, and five representative pre-trained transfer learning (TF) networks, such as Inception-v3 and Xception, were employed to establish prediction models. A comprehensive analysis was performed using five-fold cross-validation to avoid overfitting, and accuracy (ACC) and area under the receiver operating characteristic curve (AUROC) to evaluate model performance. Xception achieved the superior results when using solely tumor regions, with highest AUROCs of 0.844 (95% CI 0.841, 0.847) and 0.784 (95% CI 0.781, 0.788) for estrogen receptor (ER) and progesterone receptor (PR), respectively, and best ACC of 0.467 (95% CI 0.462, 0.470) for PAM50 subtypes. A significant improvement in the model performance was observed when images of the peri-tumor region were included, with optimal results achieved using images of the tumor and the 10 mm peri-tumor regions. Xception-based TF models performed most effectively in predicting ER and PR statuses, with the AUROCs were 0.942 (95% CI 0.940, 0.944) and 0.920 (95% CI 0.917, 0.922), respectively, whereas for PAM50 subtypes, the Inception-v3-based network yielded the highest ACC as 0.742 (95% CI 0.738, 0.746). Transfer learning analysis based on DCE-MRI data of tumor and peri-tumor regions was helpful to the non-invasive assessment of molecular characteristics of BC.

Sodium arsenite but not aluminum chloride stimulates ABC transporter activity in renal proximal tubules of killifish (Fundulus heteroclitus).

ABC export proteins including Multidrug resistance-related protein 2 (Mrp2) serve as detoxification mechanism in renal proximal tubules due to active transport of xenobiotics and metabolic waste products into primary urine. The environmental pollutants aluminum and arsenic interfere with a multitude of regulatory mechanisms in the body and here their impact on ABC transporter function was studied. NaAsO

Raman microspectroscopy based TNM staging and grading of breast cancer.

The tumor-node-metastasis (TNM) system is the most common way that doctors determine the anatomical extent of cancer on the basis of clinical and pathological criteria. In this study, a spectral histopathological study has been carried out to bridge Raman micro spectroscopy with the breast cancer TNM system. A total of seventy breast tissue samples, including healthy tissue, early, middle, and advanced cancer, were investigated to provide detailed insights into compositional and structural variations that accompany breast malignant evolution. After evaluating the main spectral variations in all tissue types, the generalized discriminant analysis (GDA) pathological diagnostic model was established to discriminate the TNM staging and grading information. Moreover, micro-Raman images were reconstructed by K-means clustering analysis (KCA) for visualizing the lobular acinar in healthy tissue and ductal structures in all early, middle and advanced breast cancer tissue groups. While, univariate imaging techniques were adapted to describe the distribution differences of biochemical components such as tryptophan, β-carotene, proteins, and lipids in the scanned regions. The achieved spectral histopathological results not only established a spectra-structure correlations via tissue biochemical profiles but also provided important data and discriminative model references for in vivo Raman-based breast cancer diagnosis.

Development of benzene and benzothiazole-sulfonamide analogues as selective inhibitors of the tumor-associated carbonic anhydrase IX.

With an aim to develop novel potential antitumor agents, two series of benzene- and benzothiazole-sulfonamide derivatives, acting as effective human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors, have been developed using the tail approach. The synthesized compounds (XS-1 to XS-22) were assayed for the inhibition of physiologically relevant isoforms of hCA, the cytosolic CA I and II, the membrane-bound CA IV and tumor-associated CA IX. It was found the compounds of both series displayed low to medium nanomolar range inhibition against CA I, II and IX, and weak inhibition against CA IV. Some of the derivatives displayed selective inhibition towards tumor-associated CA IX isoform, within the nanomolar range. These potent compounds were also screened for their selective toxicity to evaluate their in vitro anti-proliferative effects on Human Gingival Fibroblasts (HGFs) and breast adenocarcinoma cell line (MCF7). Lastly, molecular docking studies were carried out to explain those structural requirements that were liable for the discrimination among selected human carbonic anhydrase isoforms.

A randomized, double-blind, placebo-controlled, cross-over trial to evaluate the effect of EstroSense

Some estrogen metabolites are associated with increased breast cancer risk, while others are protective. Research efforts have focused on modifiable factors, including bioactive compounds found in food or supplements, promoting estrogen profiles with anti-cancer properties. EstroSense 148 premenopausal women were recruited from British Columbia, Canada to participate in a randomized, double-blind, cross-over, multicentre, placebo-controlled study in which women were randomized to a treatment sequence that consisted of either EstroSense After 12 weeks of intervention, the mean (95% CI) urinary 2-OHE EstroSense use led to markedly higher urinary 2-OHE116α-OHE1 than the placebo, a biomarker associated with a lower risk of breast cancer. httpclinicaltrials.gov (NCT02385916).

As tumor genomic profiling (TGP) is increasingly used to help guide cancer treatment, Participants include patients at Huntsman Cancer Institute undergoing TGP through a single commercial laboratory between March 2014 and July 2018. A retrospective chart review was conducted for 62 patients found to have pathogenic variants (PVs) in In the study time frame, 1,899 patients underwent TGP. Testing identified 67 PVs in This study represents one institutions experience with genetic counseling referrals, uptake, and germline results following TGP. For some patients, TGP will be the first indicator of an underlying hereditary condition. Identifying patients with PVs (which may be germline) through TGP is an important new genetic counseling referral tool that can have important implications for the patient and their family.

Effects of Systemic Diseases on Graft Preparation in Descemet Membrane Endothelial Keratoplasty.

To evaluate the effects of the systemic diseases and drugs of the donor on Descemet membrane (DM) graft preparation. Seventy-eight corneas of 58 donors, of whom the DM grafts were used in Descemet membrane endothelial keratoplasty (DMEK) surgery, between January 2018 and January 2020, were enrolled in this retrospective study. The hospital records of the donors were analyzed. Age, sex, blood type, systemic diseases, and drugs complete blood count biochemistry panel for liver and kidney functions in the past 48 hours and the drugs used in the hospital, if any, in the past 24 hours were recorded. The grafts with tears that occurred while preparation were included in group 1, and the successful grafts with no tears were included in group 2. There were no statistically significant differences in the characteristics of the donors between groups. However, breast cancer and the use of sevelamer were found to be significantly higher in group 1 ( P 0.010, P 0.033, respectively). No statistically significant difference in the use of other drugs was found between groups. Although diabetic donors have been reported to be inappropriate candidates for the preparation of DM grafts for DMEK, most of the donors with several systemic diseases including diabetes can be used in DMEK surgery, with the right technique in DM graft preparation.

Analytical and clinical characterization of an optimized dual monoclonal sandwich ELISA for the quantification of thymidine kinase 1 (TK1) protein in human blood samples.

Thymidine Kinase 1 (TK1) plays an important role in DNA precursor synthesis and serum TK1 activity has been used as a biomarker for prognosis and therapy monitoring of different malignancies. AroCell has developed a dual monoclonal antibody ELISA for determination of TK1 protein in clinical samples. The purpose of the study is to validate the ELISA analytically in relation to the gold standard, 3H-deoxythymidine (dThd) phosphorylation assay for TK1 activity using sera from patients with different malignancies. The colorimetric TK 210 ELISA was validated analytically by assessment of precision, linearity, interfering substances, and stability. For the clinical validation, serum samples from patients with hematological malignancies (n 100), breast cancer (n 56), prostate cancer (n 70) and blood donors (n 159) were analyzed using TK 210 ELISA and TK1 activity by 3H-deoxythymidine (dThd) phosphorylation assay. The sandwich TK 210 ELISA was highly specific for TK1 protein having a detection limit of 0.12 ngmL, with a functional sensitivity of 0.25 ngmL. Within-run CVs ranged from 5.5% to 10% and between-run CVs ranged from 5% to 15%. The ratio of observed to expected dilutional parallelism of 5 serum samples was in the range of 80-120%. Samples exhibited stability through four freezethaw cycles and 5 days at 4°C. Further, the ROC curve analysis showed that TK 210 ELISA and 3H-dThd phosphorylation assay had similar sensitivity (62% vs 59%) in hematological malignancies. However, in the case of breast and prostate cancer sera, TK 210 ELISA had higher sensitivity (59% and 44%) compared to 3H-dThd phosphorylation assay (47% and 25%) at a specificity of 98%. These data demonstrate that the dual monoclonal antibody based AroCell TK 210 ELISA is a robust, accurate and precise tool for measuring TK1 protein in different malignancies that can improve the clinical applications of TK1 as a biomarker in cancer management.

Patterns of cancer in Wolaita Sodo University Hospital South Ethiopia.

Variations in cancer occurrence between populations in different places are expected because of many factors. In Ethiopia there is no national cancer registry and here we are reporting the pattern of cancer in Wolaita Sodo University hospital located in Southern region of Ethiopia with catchment area of over ten million peoples. A retrospective record analysis of all pathologically confirmed malignancies from January 2021 up to June 2021. Data was filtered and descriptive analysis was done using IBM SPSS version 22 (Chicago IL USA). In the Wolaita Sodo University Teaching Referral Hospital during the first six months of 2021, out of 1,810 histopathologically tested samples 19.5% (354) were confirmed malignant cases. Among 354 patient samples, most of them (62.4%) were in females and the rest (37%) found to be in males. The age pattern shows occurrence of 336 (95%) cases in adults and 18 (5%) cases in children. Breast cancer, soft tissue sarcomas, cancer of uteri cervix, non melanomatous skin cancer, and non hodgkin lymphomas were the five top common cancers of all age groups. In adult population, breast cancer, soft tissue sarcomas, and cancer of uteri cervix are the most common. In children of age less than 14 years non hodgkin lymphomas, soft tissue sarcomas and bone sarcomas were the three top cancers. Breast cancer, cancer of uteri cervix and soft tissue sarcomas are found to be the commonest cancers in females. On the other hand, soft tissue sarcomas, non melanomatous skin cancers and Non Hodgkin lymphomas, are the three top commonest cancers in males. Based on our current study cancer is one of the common finding from histopathology samples analyzed at the hospital and the pattern of cancer was similar to those reported in other regions of the country as well as neighboring countries. However, Comprehensive demographic and clinical data using population or facility-based cancer registry is required to get better information. Additionally, our finding of higher proportion of soft tissue sarcomas both in males and females of all age groups in this region is disparate and requires further investigation.

Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer Investigations through computational, molecular docking and conceptual DFT studies.

Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as PDB 6CBZ, 1FDW, 5GWK and 2WTT) with the selected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. The molecular docking result showed that among 44 compounds, two of them, Ashwagandhanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid -dehydrogenase type 1 (17β-HSD1), topoisomerase II alpha (TOP2A) and p73 tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties confirmed that Ashwagandhanolide is hydrophobic and has moderate intestinal permeability, good intestinal absorption, and poor skin permeability. The compound has a relatively low VDss value (-1.652) and can be transported across ABC transporter and good central nervous system (CNS) permeability but did not easily cross the blood-brain barrier (BBB). This compound does not possess any mutagenicity, hepatotoxicity and skin sensitization. Based on the results obtained, the present study highlights the anticancer potential of Ashwagandhanolide, a compound from W. somnifera. Furthermore, in vitro and in vivo studies are necessary to perform before clinical trials to prove the potentiality of Ashwagandhanolide.

Delayed diagnostic evaluation of symptomatic breast cancer in sub-Saharan Africa A qualitative study of Tanzanian women.

Women with breast cancer in sub-Saharan Africa are commonly diagnosed at advanced stages. In Tanzania, more than 80% of women are diagnosed with stage III or IV disease, and mortality rates are high. This study explored factors contributing to delayed diagnostic evaluation among women with breast cancer in Tanzania. A qualitative study was performed at Muhimbili National Hospital in Dar es Salaam, Tanzania. Twelve women with symptomatic pathologically proven breast cancer were recruited. In-depth, semi-structured interviews were conducted in Swahili. Interviews explored the womens journey from symptom recognition to diagnosis, including the influence of breast cancer knowledge and pre-conceptions, health seeking behaviors, psychosocial factors, preference for alternative treatments, and the contribution of culture and norms. Audio-recorded interviews were transcribed and translated into English. Thematic analysis was facilitated by a cloud-based qualitative analysis software. All women reported that their first breast symptom was a self-identified lump or swelling. Major themes for factors contributing to delayed diagnostic presentation of breast cancer included lack of basic knowledge and awareness of breast cancer and misconceptions about the disease. Participants faced barriers with their local primary healthcare providers, including symptom mismanagement and delayed referrals for diagnostic evaluation. Other barriers included financial hardships, fear and stigma of cancer, and use of traditional medicine. The advice and influence of family members and friends played key roles in healthcare-seeking behaviors, serving as both facilitators and barriers. Lack of basic knowledge and awareness of breast cancer, stigma, financial barriers, and local healthcare system barriers were common factors contributing to delayed diagnostic presentation of breast cancer. The influence of friends and family also played key roles as both facilitators and barriers. This information will inform the development of educational intervention strategies to address these barriers and improve earlier diagnosis of symptomatic breast cancer in Tanzania.

Health system cost of breast cancer treatment in Addis Ababa, Ethiopia.

Breast cancer is the leading cancer among women with an annual crude incidence of 27.4 per 100,000 in Ethiopia. The aims of this study were to (a) estimate the unit cost of breast cancer treatment for the standard Ethiopian patient, (b) identify the cost drivers, (c) project the total cost of breast cancer treatment for the next five years, and (d) estimate the economic burden of the disease in the main specialized tertiary hospital-Tikur Anbessa Specialized Hospital (TASH) Addis Ababa. Primary data were collected from health and non-health professionals. Secondary data were collected from patients charts and official reports from various national and international organisations including data from TASH. To establish work-time estimates, we asked professionals on their time usage. A total of US$ 33,261 was incurred to treat 52 Addis Ababa resident female breast cancer patients in TASH between July 2017 and June 2019. The unit cost of treatment for a hypothetical breast cancer patient to complete her treatment was US$ 536 for stage I and US$ 705 for stage II and III using the existing infrastructure. This cost increased to US$ 955 for stage I and US$ 1157 for stage II and III when infrastructure amortization was considered. The projected total costs of breast cancer treatment in TASH is between US$ 540,000 and US$ 1.48million. However, this will increase to US$ 870,000 and US$ 2.29 million when the existing fixed assets are changed. The economic burden of breast cancer treatment is high compared to the economic status of the country. Thus, it is recommended that TASH should revise its charges and breast cancer should be included in the Social and Community based health insurance scheme. JEL classification H51, H75, I18, P46.

Effectiveness of Selective Estrogen Receptor Modulators in Breast Cancer Therapy An Update.

Breast cancer is considered to be 2nd most common cancer subtype investigated worldwide. It is mainly prevalent in postmenopausal women. Estrogen Receptor (ER) is a primary transcription factor for survival and growth of tumors. Around 80% BCs of all classes are ER-positive (ER). Powerful evidence for estrogen proved to be involved in BC pathogenesis both exogenously and endogenously. It brings the concept of ER inhibitors to treat BC with distinct mechanisms into focus and ER PROTACs (Proteolysis-Targeting Chimeras), AIs (Aromatase inhibitors), SERMs (Selective estrogen receptor modulators), and SERDs (Selective estrogen receptor degrader) were developed. For over 30 years, Tamoxifen, a triphenylethylene SERM, was the drug of choice solely to treat ERBC patients. Although several SERMs got approval by US FDA after tamoxifen, complicacies remain because of dangerous adverse effects like endometrial carcinoma, hot flashes, and VTE (Venous thromboembolism). In addition to that drug-resistant tumors put a surging need for novel, potent candidates with no or low adverse effects for ER BC prevention. This article explores the possibilities of SERMs as effective BC agents. A detailed literature survey of the history and recent advancements of SERMs has been carried out, taking BC as the primary target. This review provides information about ER structure, signaling, pharmacological action, chemical classification with SAR analysis, benefits and adverse effect of SERMs as potential BC agents. Exhaustive literature studies suggested that SERMs having an agonistic, antagonistic or mixed activity to ER could efficiently inhibit BC cell proliferation. Each chemical class of SERMs comprises of some salient features and potentials, which may be further investigated to obtain novel effective SERMs in BC therapy.

Surrogacy of Pathologic Complete Response in Trials of Neoadjuvant Therapy for Early Breast Cancer Critical Analysis of Strengths, Weaknesses, and Misinterpretations.

The pathologic complete response (pCR) is supported by regulatory agencies as a surrogate end point for long-term patients clinical outcomes in the accelerated approval process of new drugs tested in neoadjuvant randomized clinical trials (RCTs) for early breast cancer (BC). However, a meaningful association between pCR and patients survival has been proven only at the patient level (ie, significantly better survival of patients who achieved pCR compared with those who did not), but not at trial level (ie, poor association between degree of improvement in pCR rate and survival reported across trials). We critically discuss the potential reasons of such discrepancy between pCR surrogacy value at the patient and trial level, as well as the relevant implications for both clinical research and drug regulatory policy. We also describe alternative surrogate end points, including combined end points that jointly analyzed pathological response and event-free survival data, or the assessment of circulating tumor DNA (ctDNA). Such proposed surrogate end points could overcome limits of pCR and provide a reasonable trade-off between the 2 conflicting needs to have access to effective therapies rapidly, and to reliably assess patients clinical benefit. Using surrogate end points to grant drug approvals is justified only when they can provide accurate prediction of a drugs effect on the long-term patient outcomes. Evidence currently available does not support pCR used alone as a reliable surrogate end point in regulatory neoadjuvant RCTs for BC. The surrogacy value at trial level of potentially more robust surrogate end points needs to be urgently tested.

Epidemiology of interstitial lung disease in patients with metastatic breast cancer at baseline and after treatment with HER2-directed therapy a real-world data analysis.

Using real-world data, interstitial lung disease (ILD) prevalence before and after HER2-directed therapy was estimated. Potential ILD risk factors in patients receiving HER2-directed therapy for metastatic breast cancer (mBC) were evaluated. Adults with HER2-directed therapy for mBC initiated between September 25, 1998, and February 22, 2020 were, included. ILD was defined broadly as one or more of 64 lung conditions. Patients were followed until incident ILD, death, last contact, or study end. In total, 533 patients were identified with median age at mBC of 57, 51% had de novo mBC, 43% were ever smokers, 30% had lung metastases, 9% had thoracic radiation, 6% had chronic obstructive pulmonary disease, and 16% had prevalent ILD. ILD cumulative incidence at one year was 9% (95% CI 6%, 12%), with a median follow-up of 23 months. Smoking (HR 2.2, 95% CI 1.1, 4.8) and BlackAfrican-American race (HR 3.4, 95% CI 1.6, 7.5) were significantly associated with ILD HRs for preexisting lung conditions (HR 1.8, 95% CI 0.9, 3.8) and thoracic radiation (HR 2.3, 95% CI 0.8, 7.1) were not statistically significant. Prevalent ILD was associated with 13-fold greater occurrence of incident ILD. 85% of patients with prevalent or incident ILD were symptomatic. This real-world population of patients with mBC had a high prevalence of ILD prior to HER2-directed therapy, reflecting the multifactorial causation of interstitial lung changes. The cumulative incidence of ILD in patients receiving HER2-directed therapy for mBC augments prior reports. Symptomatic presentation suggests an opportunity for early intervention.

The Italian Association for Radiotherapy and Clinical Oncology (AIRO) position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation.

Recent advances in non-metastatic breast cancer radiation therapy significantly reshaped our views on modern dose and fractionation schedules. Especially the advent of hypofractionation and partial breast irradiation defined a new concept of treatment optimization, that should strongly include both patient and tumour characteristics in the physicians decision-making process. Unfortunately, hypofractionation for breast cancer radiation therapy needed long time to enter the routine practice during the last decades despite the level-1 evidence published over time. Hereby we present the Italian Association for Radiotherapy and Clinical Oncology (AIRO) Breast Cancer Group position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation to harmonically boost routine clinical practice implementation following evidence-based data.

Sleep disturbance in cancer survivors with lymphedema a scoping review.

The purpose of this study is to identify the amount and scope of knowledge on sleep disturbance in cancer survivors who have lymphedema. The research question investigated was what are the known sleep disturbances in cancer survivors with lymphedema A literature search was performed on February 15 to March 27, 2021, in four databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) and structure recommended by Arksey and OMalley. An iterative process of study selection was performed by two reviewers for abstract and full-text review. The Joanna Briggs Institutes critical appraisal tools were used to analyze study quality. One hundred twenty-one unique references were reviewed, and seven met the inclusion criteria. One article had the primary aim of assessing sleep and noted that the presence of lymphedema did increase the risk for sleep disturbance. Four cross-sectional studies compared sleep quality between cancer survivors with lymphedema and cancer survivors without lymphedema. These studies found that lymphedema is a significant predictor of insomnia and is a risk factor for insomnia. Two randomized control trials compared sleep among breast cancer survivors with lymphedema after an intervention. Sleep improved with a yoga intervention and was unchanged after adding a night-time compression garment. In this scoping review, breast and gynecological cancer survivors with lymphedema report increased sleep disturbance compared to survivors without lymphedema. Further research is needed to characterize the specific sleep disturbances in cancer survivors with lymphedema for improved screening and treatment.

Aberrant phosphorylation inactivates Numb in breast cancer causing expansion of the stem cell pool.

Asymmetric cell division is a key tumor suppressor mechanism that prevents the uncontrolled expansion of the stem cell (SC) compartment by generating daughter cells with alternative fates one retains SC identity and enters quiescence and the other becomes a rapidly proliferating and differentiating progenitor. A critical player in this process is Numb, which partitions asymmetrically at SC mitosis and inflicts different proliferative and differentiative fates in the two daughters. Here, we show that asymmetric Numb partitioning per se is insufficient for the proper control of mammary SC dynamics, with differential phosphorylation and functional inactivation of Numb in the two progeny also required. The asymmetric phosphorylationinactivation of Numb in the progenitor is mediated by the atypical PKCζ isoform. This mechanism is subverted in breast cancer via aberrant activation of PKCs that phosphorylate Numb in both progenies, leading to symmetric division and expansion of the cancer SC compartment, associated with aggressive disease. Thus, Numb phosphorylation represents a target for breast cancer therapy.

Boosting immunotherapy of triple negative breast cancer through the synergy of mild PTT and Fe-loaded organosilica nanoparticles.

Triple negative breast cancer (TNBC) is associated with drug resistance, metastasis, and poor immune response. The development of novel strategies to evoke a robust immune response against TNBC is necessary. In this study, we propose a TNBC tumor immunotherapy modality by synergizing nanocatalytic medicine with mild photothermal therapy. Briefly, mesoporous organosilica nanoparticles (MONs) and an Fe

A new cembranoid from the Red Sea soft coral

The Red Sea soft coral

Targeting to Tumor-Harbored Bacteria for Precision Tumor Therapy.

The differential tumor environment guides various antitumor drug delivery strategies for efficient cancer treatment. Here, based on the special bacteria-enriched tumor environment, we report a different drug delivery strategy by targeting bacteria inhabiting tumor sites. With a tissue microarray analysis, it was found that bacteria amounts displayed significant differences between tumor and normal tissues. Bacteria-targeted mesoporous silica nanoparticles decorated with bacterial lipoteichoic acid (LTA) antibody (LTA-MSNs) could precisely target bacteria in tumors and deliver antitumor drugs. By the intravenous administration of bacteria-targeted nanoparticles, we showed in mice with colon cancer, lung cancer, and breast cancer that LTA-MSNs exhibited a high tumor-targeting ability. As a proof-of-concept study, tumor microbes as some of the characteristics of a tumor environment could be utilized as potential targets for tumor targeting. This bacteria-guided tumor-targeting strategy might have great potential in differential drug delivery and cancer treatment.