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Breast cancer is the most common type of cancer that affect women and yet there is no substantive cure. On early diagnosis of breast lesions with this size using mammogram would help the affected tumor patients have a good survival rate. Detecting cancer cells is a challenging task and hence we propose a single valued neutrosophic approach for segmenting breast tumor lesions in mammogram images. In this neutrosophic approach, the intensity values are represented as truth, indeterminacy and falsity membership in where the indeterminacy are noise, and the breast regions are the true and falsity values. The computations of these memberships are then pre-processed using α-mean­ and ­β-enhancement to minimize the indeterminacy. Finally, gamma clustering techniques are used to localize and segment the tumor from the background breast tissue region. Experiments are conducted on publicly available datasets and the proposed method is evaluated and achieves a better segmentation performance. [ABSTRACT FROM AUTHOR]

Normal tissues adjacent to the tumor (NATs) may harbor early breast carcinogenesis events driven by field cancerization. Although previous studies have characterized copy-number (CN) and transcriptomic alterations, the evolutionary history of NATs in breast cancer (BC) remains poorly characterized. Utilizing whole-genome sequencing (WGS), methylation profiling, and RNA sequencing (RNA-seq), we analyzed paired germline, NATs, and tumor samples from 43 individuals with BC in Hong Kong (HK). We found that single-nucleotide variants (SNVs) were common in NATs, with one-third of NAT samples exhibiting SNVs in driver genes, many of which were present in paired tumor samples. The most frequently mutated genes in both tumor and NAT samples were PIK3CA , TP53 , GATA3 , and AKT1. In contrast, large-scale aberrations such as somatic CN alterations (SCNAs) and structural variants (SVs) were rarely detected in NAT samples. We generated phylogenetic trees to investigate the evolutionary history of paired NAT and tumor samples. They could be categorized into tumor only, shared, and multiple-tree groups, the last of which is concordant with non-genetic field cancerization. These groups exhibited distinct genomic and epigenomic characteristics in both NAT and tumor samples. Specifically, NAT samples in the shared-tree group showed higher number of mutations, while NAT samples belonging to the multiple-tree group showed a less inflammatory tumor microenvironment (TME), characterized by a higher proportion of regulatory T cells (Tregs) and lower presence of CD14 cell populations. In summary, our findings highlight the diverse evolutionary history in BC NAT/tumor pairs and the impact of field cancerization and TME in shaping the genomic evolutionary history of tumors. [Display omitted] Analysis of normal tissues adjacent to breast tumors (NATs) revealed widespread somatic point mutations, including in cancer driver genes, but few large-scale chromosomal aberrations. Further analysis uncovered different cancer evolution patterns influenced by the tumor microenvironment (TME). This study highlights the roles of field cancerization and the TME in breast cancer (BC) evolution. [ABSTRACT FROM AUTHOR]

Background: Endoscopic‐assisted breast surgery (EABS) provides better cosmetic outcomes for breast cancer patients with small incisions in an inconspicuous area. However, an extended incision and heavy assistant retraction are usually required for an adequate exposure for conventional axillary lymph node dissection (ALND). Therefore, we propose an innovative single‐port three‐dimensional endoscopic‐assisted ALND (S‐P 3D E‐ALND) to facilitate better visualization, and report its preliminary outcomes herein. Methods: The surgical technique of the S‐P 3D E‐ALND, using either monopolar Endo Hook, LigaSure, or Sonicision, is described. A total of 11 breast cancer patients who received the S‐P 3D E‐ALND in a single institution from January 2023 to September 2023 were enrolled. The preliminary results of the S‐P 3D E‐ALND, including perioperative parameters, complication, and short‐term oncological outcomes, were retrospectively analyzed. Results: Endoscopic breast and axillary procedures were conducted via a single axillary incision. The primary success rate of the S‐P 3D E‐ALND was 100% without a conversion to open surgery. The median operative time for the S‐P 3D E‐ALND was 39 (IQR = 28, 49) minutes. Average blood loss during E‐ALND was 3 (IQR = 3, 5) mL. The median number of harvested LN was 10 (IQR = 8, 11) LNs. During the median follow‐up time of 7 months, there was no complication, lymphedema, shoulder stiffness, or chronic arm numbness found. None of the patients reported locoregional recurrence, distant metastasis, or mortality. Conclusion: The S‐P 3D E‐ALND can serve as an alternative approach for ALND in breast cancer patients undergoing EABS, as our findings indicate it results in only minor complications. [ABSTRACT FROM AUTHOR]

Introduction Pain is a prevalent side effect seen in breast cancer survivors (BCS). Psychological factors are known role players in pain mechanisms. Both pain and psychological factors contribute to or interact with healthcare use (HCU). However, the association between psychological factors and HCU has never been investigated in BCS with pain, which is the aim of the present study. Methods Belgian BCS with pain (n  = 122) were assessed via the Medical Consumption Questionnaire, the Injustice Experienced Questionnaire, the Pain Catastrophizing Scale, the Pain Vigilance and Awareness Questionnaire, the Brief Illness Perceptions Questionnaire, and the Depression, Anxiety, and Stress Scale. Associations were analyzed with logistic and Poisson regressions. Results Opioid use was related to more catastrophizing and less psychological distress. Psychotropic drug use was related to more psychological distress. Endocrine therapy was related to less vigilance and awareness. Psychological distress was related to all types of healthcare provider (HCP) visits, with psychological distress negatively related to physiotherapy, psychology, and other primary HCP visits, and positively related to visiting a general practitioner or secondary HCP. Catastrophizing was related to more visiting behavior to a primary HCP, except to a general practitioner. Perceived injustice was related to more general practitioner and other primary HCP visits but to fewer psychology visits. Illness perceptions were related only to visiting other primary HCPs. Vigilance and awareness were related to more psychologist and secondary HCP visits. Conclusion Our findings underscore the complex interplay between HCU and psychological factors in BCS with pain. Psychological distress was overall the most important psychological factor related to HCU, whether catastrophizing and perceived injustice were the most relevant related to HCP visits. [ABSTRACT FROM AUTHOR]

Introduction: In silico tools capable of predicting the functional consequences of genomic differences between individuals, many of which are AI-driven, have been the most effective over the past two decades for non-synonymous single nucleotide variants (nsSNVs). When appropriately selected for the purpose of the study, a high predictive performance can be expected. In this feasibility study, we investigate the distribution of nsSNVs with an allele frequency below 5%. To classify the putative functional consequence, a tier-based filtration led by AI-driven predictors and scoring system was implemented to the overall decision-making process, resulting in a list of prioritised genes. Methods: The study has been conducted on breast cancer patients of homogeneous ethnicity. Germline rare variants have been sequenced in genes that influence pharmacokinetic parameters of anticancer drugs or molecular signalling pathways in cancer. After AI-driven functional pathogenicity classification and data mining in pharmacogenomic (PGx) databases, variants were collapsed to the gene level and ranked according to their putative deleterious role. Results: In breast cancer patients, seven of the twelve genes prioritised based on the predictions were found to be associated with response to oncotherapy, histological grade, and tumour subtype. Most importantly, we showed that the group of patients with at least one rare nsSNVs in cystic fibrosis transmembrane conductance regulator (CFTR) had significantly reduced disease-free (log rank, p = 0.002) and overall survival (log rank, p = 0.006). Conclusion: AI-driven in silico analysis with PGx data mining provided an effective approach navigating for functional consequences across germline genetic background, which can be easily integrated into the overall decision-making process for future studies. The study revealed a statistically significant association with numerous clinicopathological parameters, including treatment response. Our study indicates that CFTR may be involved in the processes influencing the effectiveness of oncotherapy or in the malignant progression of the disease itself. [ABSTRACT FROM AUTHOR]

Diet and physical activity guidelines for cancer survivorship are less likely to be followed by populations of minority cancer survivors, such as Latina/Hispanic women, compared to non-Hispanic White women. It is important to understand psychosocial mechanisms that may increase adherence to healthy lifestyle habits, especially in populations at risk for poorer cancer outcomes. This cross-sectional study examined the relationships between overall social support (SS) and SS from three sources (family, friends, and significant other) with diet (fruit and vegetables, fat, energy density, and diet quality), and moderate-to-vigorous physical activity (MVPA) behaviors in Latina/Hispanic women with a history of breast cancer (n = 85; M age = 55.2; SD = 9.2). Linear regression models and odds ratios were used to examine associations and adjusted for age, income, and acculturation. Family, significant other, and total SS were positively related to total fruit and vegetable intake but SS from friends was not. Higher levels of SS from all sources were each related to a low energy density diet. A higher quality diet was only related to SS from family. SS was not related to fat intake or MVPA. Higher SS from family and a significant other were associated with higher odds of meeting the fruit/vegetable guidelines; (family, OR = 3.72, 95% CI [1.21, 11.39]; significant other, OR = 3.32, 95% CI [1.08, 10.30]). Having more SS from family or a significant other may contribute to Latina/Hispanic women breast cancer survivors meeting national guidelines for a diet high in fruits and vegetables and low in energy density. [ABSTRACT FROM AUTHOR]

This nationwide study provides an overview of trends and variations in radiotherapy use as part of multimodal treatment of invasive non-metastatic breast cancer in the Netherlands in 2008–2019. Women with invasive non-metastatic breast cancer were selected from the population-based Netherlands Cancer Registry. Treatments trends were presented over time. Factors associated with (1) boost irradiation in breast-conserving therapy and (2) regional radiotherapy instead of axillary lymph node dissection (ALND) in N+ disease were identified using multilevel logistic regression analyses. Radiotherapy use increased from 61% (2008) to 70% (2016), caused by breast-conserving therapy instead of mastectomy, increased post-mastectomy radiotherapy, and increased regional radiotherapy (32% in 2011 to 61% in 2019) instead of ALND in N+ disease. Omission of radiotherapy after breast-conserving surgery (BCS) in 2016–2019 (4–9%, respectively), mainly in elderly, decreased overall radiotherapy use to 67%. Radiotherapy treatment was further de-escalated by decreased boost irradiation in breast-conserving therapy (66% in 2011 to 37% in 2019) and partial (1% in 2011 to 6% in 2019) instead of whole breast irradiation following BCS. Boost irradiation was associated with high-risk features: younger age (OR>75 vs <50:0.04, 95%CI:0.03–0.05), higher grade (OR grade III vs I:11.46, 95%CI:9.90–13.26) and residual disease (OR focal residual vs R0-resection:28.08, 95%CI:23.07–34.17). Variation across the country was found for both boost irradiation use (OR South vs North:0.58, 95%CI:0.49–0.68), and regional radiotherapy instead of ALND (OR Southwest vs North:0.55, 95%CI:0.37–0.80). Overall radiotherapy use increased in 2008–2016, while a decreasing trend was observed after 2016, caused by post-BCS radiotherapy omission. Boost irradiation in breast-conserving therapy became omitted in low-risk patients, and regional radiotherapy use increased as an alternative for ALND in N+ disease. • Overall radiotherapy (RT) use in M0 breast cancer increased in 2008–2016 (61–70%). • Thereafter, RT use decreased to 67% (2019) because of post-BCS RT omission in elderly. • Breast-conserving therapy: boost use decreased, partial breast irradiation increased. • Low-risk patients less likely received boost irradiation in breast-conserving therapy. • Regional RT was increasingly used as alternative for ALND in nodal disease. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to examine the effectiveness of a web application on health literacy and self‐efficacy in managing arm oedema symptoms among patients with breast cancer. Methods: The research was carried out in four phases as follows: Phase 1, using a qualitative approach to explore problems and information needs in educating breast cancer patients through in‐depth interviews with 10 professional nurses who had experiences in caring for breast cancer patients and 20 breast cancer patients. Data were analysed by content analysis; Phase 2, designing and developing a web application and confirming its quality by five experts with experience caring for breast cancer patients; Phase 3, testing the web application with five breast cancer patients; and Phase 4, examining the effectiveness of a web application in breast cancer patients using a quasiexperimental research method. Patients were divided into 15 persons in control and 15 in intervention groups, a total of 30 persons. The tools used in the study consisted of (1) a web application on practices for reducing risk for arm oedema after breast cancer treatment, (2) a health literacy assessment tool, (3) a self‐efficacy for managing symptoms questionnaire and (4) a web application satisfaction questionnaire. Data were analysed using descriptive statistics, chi‐square and t test. Results: Qualitative findings: The web application should cover patients' and nurses' views on arm oedema causes, assessment, prevention and self‐care for managing swelling after breast cancer treatment. Characteristics of a web application required: large text, bright colours, clear visibility, accompanying pictures or videos, using simple language without official terminology, easy to access, convenient to use, concise, interesting content and shareable to others. Quantitative findings: The intervention group had significantly higher health literacy and self‐efficacy in managing symptom scores than before the trial (p < 0.001). Sample groups were satisfied with the developed web application at a high level. When considering each item, it was found that all items were rated at high levels. Two items with the same highest score were ease of use and the attractiveness of the presentation style. Conclusion: This web application, aimed at reducing the risk of arm oedema after breast cancer treatment, is an effective tool for educating all hospitalized patients. In addition, further research should be conducted to monitor the sustainability of long‐term and clinical outcomes. Summary statement: What is already known about this topic? Some patients with breast cancer experience arm oedema either immediately after treatment or over extended periods.Web applications have become a valuable tool for educating patients with breast cancer. However, the features of the web applications designed to reduce the risk of breast cancer‐related lymphedema and their effectiveness remain unclear. What this paper adds? An effective web application for preventing breast cancer‐related lymphedema should cover causes, assessment, prevention strategies and self‐management guidelines. Key features should include large text, user‐friendly design, attractiveness and clarity.Web applications can help patients with breast cancer improve health literacy and self‐efficacy in managing symptoms. The implications of this paper: The web application should be used to educate breast cancer patients. [ABSTRACT FROM AUTHOR]

Context.--Low-grade fibromatosis-like metaplastic carcinoma (FLMC) is a very rare subtype of triple-negative metaplastic (spindle cell) breast carcinoma. It is characterized by the proliferation of spindle cells closely resembling fibromatosis, which represents a benign fibroblastic/myofibroblastic breast proliferation. Unlike most triple-negative and basal-like breast cancers, FLMC has a very low potential for metastases, but demonstrates frequent local recurrences. Objective.--To genetically characterize FLMC. Design.--To this end, we analyzed 7 cases by targeted next-generation sequencing for 315 cancer-related genes and performed comparative microarray copy number analysis in 5 of these cases. Results.--All cases shared TERT alterations (6 patients with recurrent c.-124C.T TERT promoter mutation and 1 patient with copy number gain encompassing the TERT locus), had oncogenic PIK3CA/PIK3R1 mutations (activation of the PI3K/AKT/mTOR pathway), and lacked mutations in TP53. TERT was overexpressed in all FLMCs. CDKN2A/B loss or mutation was observed in 4 of 7 cases (57%). Furthermore, tumors displayed chromosomal stability, with only few copy number variations and a low tumor mutational burden. Conclusions--We conclude that FLMCs typically show the recurrent TERT promoter mutation c.-124C.T, activation of the PI3K/AKT/mTOR pathway, low genomic instability, and wild-type TP53. In conjunction with previous data of metaplastic (spindle cell) carcinoma with and without fibromatosis-like morphology, FLMC is most likely distinguished by TERT promoter mutation. Thus, our data support the notion of a distinct subgroup within low-grade metaplastic breast cancer with spindle cell morphology and associated TERT mutations. [ABSTRACT FROM AUTHOR]

Context.--Quantitative imaging is a promising tool that is gaining wide use across several areas of pathology. Although there has been increasing adoption of morphologic and immunohistochemical analysis, the adoption of evaluation of fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue has been limited because of complexity and lack of practice guidelines. Objective.--To perform human epidermal growth factor receptor 2 (HER2) FISH validation in breast carcinoma in accordance with the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 guideline. Design.--Clinical validation of HER2 FISH was performed using the US Food and Drug Administration- approved dual-probe HER2 IQFISH (Dako, Carpinteria, California) with digital scanning performed on a PathFusion (Applied Spectral Imaging, Carlsbad, California) system. Validation parameters evaluated included z-stacking, classifier, accuracy, precision, software, and hardware settings. Finally, we evaluated the performance of digital enumeration on clinical samples in a real-world setting. Results.--The accuracy samples showed a final concordance of 95.3% to 100% across HER2 groups 1 to 5. During clinical implementation for HER2 groups 2, 3, and 4, we achieved a final concordance of 76% (95 of 125). Of these cases, only 8% (10 of 125) had discordances with clinical impact that could be identified algorithmically and triaged for manual review. Conclusions.--Digital FISH enumeration is a useful tool to improve the efficacy of HER2 FISH enumeration and capture genetic heterogeneity across HER2 signals. Excluding cases with high background or poor image quality and manual review of cases with ASCO/CAP group discordances can further improve the efficiency of digital HER2 FISH enumeration. [ABSTRACT FROM AUTHOR]

The aim of the study is to determine body image, sexual adjustment and the factors affecting them in women with breast cancer after surgery. This descriptive and cross-sectional study was conducted with breast cancer patients admitted to a foundation hospital. Data were collected with the Sexual Adjustment and Body Image Scale, evaluated with t-test, MWU, Kruskall Wallis and correlation analysis. Sexual Adjustment Body Image scale subdimension scores of the patients were 10.81±2.32 for Prior Body Image, 9.69±2.69 for Postbody Image,7.04±1.73 for Prior Sexual Adjustment,7.4±2.34 for Sexual Importance of Breasts and -4.28±2.63 for Impact on Sexual Functioning. A weak positive correlation was found between the patients' body image scores and their sexual adjustment scores. It was found that having a child significantly affected the Prior and Postbody Image scores. There was a significant difference between Prior Sexual Adjustment scores according to income level. Employment had an effect on the Impact on Sexual Functioning subdimension score and presence of a chronic disease affected the Postbody Image and Prior Sexual Adjustment subdimension scores. Having a chronic disease, having children, being employed, and having poor income affect sexual adjustment and body image in women with breast cancer after surgery. [ABSTRACT FROM AUTHOR]

Background: Improving quality of life (QOL) in advanced and metastatic cancer is a priority with increasing survivorship. This systematic review synthesizes psychosocial and behavioral interventions incorporating culture with the goal of examining their benefit for understudied and medically underserved populations with advanced and metastatic cancer. Method: Reports were systematically screened for (1) a focus on advanced and metastatic cancer survivors, (2) psychosocial or behavioral intervention intended to improve QOL, (3) evidence of incorporating the culture(s) of understudied/underserved populations, and (4) availability in English. Bias was evaluated using the JBI Critical Appraisal Checklist and the Methodological index for non‐randomized studies. Qualitative synthesis and quantitative meta-analyses were completed. Results: Eighty-six reports containing 5981 participants' data were examined. Qualitative synthesis of 23 studies identified four overarching themes relevant for incorporating culture in interventions. Meta-analysis of 19 RCTs and 4 quasi-experimental studies containing considerable heterogeneity indicated greater improvements in QOL (g = 0.84), eudaimonic well-being (g = 0.53), distress (g = −0.49), and anxiety (g = −0.37) for main intervention conditions compared to controls. Meta-analysis of 10 single-arm trials containing minimal to moderate heterogeneity found benefit for anxiety (g = −0.54), physical symptoms (g = −0.39), and depression (g = −0.38). Conclusion: Psychosocial and behavioral interventions with cultural incorporation appear beneficial for improving QOL-related outcomes in advanced and metastatic cancer. Studies incorporating culture in psychosocial or behavioral interventions offer noteworthy insight and suggestions for future efforts such as attending to deep cultural structure. [ABSTRACT FROM AUTHOR]

Purpose: Cancer survivors experience barriers to primary healthcare (PHC) services. The aim was to explore reactions to and opinions about perceived challenges associated with PHC access and quality among cancer survivors in Sweden, including how they have acted to adapt to challenges. Methods: Five semi-structured focus group interviews were conducted with cancer survivors (n = 20) from Skåne, Sweden, diagnosed with breast, prostate, lung, or colorectal cancer or malignant melanoma. Focus groups were mixed in regard to diagnosis. Data were analysed using a descriptive template analysis approach. Results: In light of perceived challenges associated with access to adequate PHC, participants experienced that they had been forced to work hard to achieve functioning PHC contacts. The demands for self-sufficiency were associated with negative feelings such as loneliness and worry. Participants believed that cancer survivors who lack the ability to express themselves, or sufficient drive, risk missing out on necessary care due to the necessity of being an active patient. Conclusions: The findings highlight negative patient experiences. They have implications for the organization of care for cancer survivors as they indicate a need for more efficient post-treatment coordination between cancer specialist care and PHC providers, as well as increased support for patients leaving primary cancer treatment. [ABSTRACT FROM AUTHOR]

This study aimed to assess the disease burden of cancer in young adults globally and the changes between 2012 and 2022. A comprehensive analysis of global cancer statistics of young adults based on data provided by GLOBOCAN 2022. The incidence and mortality estimates for cancer in young adults in 2012 and 2022 were obtained from the publication by Fidler et al. and GLOBOCAN 2022, respectively. Data were displayed descriptively and compared at the sex, global, regional, national and human development index (HDI) levels. Associations between HDI rank and cancer incidence and mortality were explored by Pearson correlation analysis. In 2022, the number of new cancer cases and deaths in young adults were estimated to be 1,227,907 and 349,550, respectively, with the age-standardised incidence rate (ASIR) and age-standardised mortality rate (ASMR) of 49.5 and 14.2 per 100,000 population. In young adults, 47.22 % of new cases were breast, thyroid and cervical cancer, while the leading causes of cancer-related death were breast, leukaemia and cervical cancer. Compared to 2012, the number of new cases and the ASIR increased by 25.89 % and 14.32 %, respectively, while the number of deaths and the ASMR decreased by 2.03 % and 10.69 %, respectively. However, cancer burden and its changes varied substantially across geographical regions, HDI levels and cancer types. In general, infection-related cancers were more common in less developed regions, but their incidence decreased significantly, while Westernised lifestyle-related cancers were more common in developed countries and their incidence is increasing. Cancer contributes substantially to health-related burdens in young adults and the overall incidence has increased dramatically in the past decade. However, the incidence and mortality of cancer in this age group varied considerably by sex, cancer type, region, country and HDI level. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer (BC) is the most diagnosed tumor among women worldwide. The aim of this study was to investigate the incidence and causes of low relative dose intensity (RDI) < 85% for taxane-based chemotherapy regimens used in the treatment of BC in Sultan Qaboos University Hospital (SQUH). Methods: This was a retrospective study that included 303 BC patients, treated with taxane-based chemotherapy protocols at SQUH. RDI was calculated for each chemotherapy regimen and causes and predictors of low RDI < 85% were identified. Prophylactic and therapeutic supportive measures for certain toxicities were studied. Results: 50.8% of the patients had neoadjuvant chemotherapy, 38% had adjuvant chemotherapy, and 11.2% of patients were given palliative treatment. AC-T and AC-THP were the most used regimens (40.3% and 17.2%). Mean RDI of used taxane-based chemotherapy regimens was 93.4%. Dose delays, dose reductions, and treatment discontinuation occurred in 36.6%, 14.8%, and 11.5%, respectively. Thirty-eight patients (12.5%) had low RDI < 85% which was reduced to 9.9% after the use of an alternative taxane. Age and chemotherapy intent were significant risk factors. 83.8% received primary granulocyte colony stimulating factor. Conclusion: An optimal RDI greater than 85% was achieved in most cases. Furthermore, prophylactic and therapeutic supportive measures were widely used. [ABSTRACT FROM AUTHOR]

Purpose: The standard of care for locally advanced, human epidermal growth factor receptor 2 positive (HER2+) breast cancer includes neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). Many patients do not receive the full course of therapy due to various complications, possibly affecting the potential to achieve a pathologic complete response (pCR). The amount of therapy received is typically measured by relative dose intensity (RDI). This study aimed to evaluate pCR rates in patients receiving optimal and suboptimal RDI TCHP. Methods: This study was a retrospective chart review of patients treated between 2014 and 2021 at UK HealthCare. Patients included were 18 years of age or older with HER2+ breast cancer and received at least one cycle of neoadjuvant TCHP. The primary objective compared pCR rates in patients receiving ≥ 85% RDI or <85% RDI. Secondary objectives included pCR rates based on clinical stage, age, body mass index, or hormone receptor status; factors leading to discontinuation or delay in treatment; and impact of dose reductions and delays on pCR. Results: A total of 101 patients were included and divided into two cohorts: 54 patients received ≥ 85% RDI and 47 patients received <85% RDI. Patients who received ≥ 85% total RDI had an approximate increase of 17% in pCR rates (59.3% vs 42.6%, p = 0.11). Additionally, 82% of patients experienced a dose delay or adjustment. Conclusions: Patients who received ≥ 85% RDI had increased pCR rates compared to patients receiving <85% RDI. A larger patient population is needed to formulate definitive conclusions on the impact of RDI and pCR rates. [ABSTRACT FROM AUTHOR]

Introduction: Patients diagnosed with cancer are at an increased risk of infection. Vaccines remain one of the most critical public health strategies in limiting infectious diseases, with a heightened importance in cancer patients. Data across the general US population indicates that vaccine adherence rates are suboptimal across all adult vaccine schedules. This study aims to define vaccine adherence rates within the oncology population. Methods: This retrospective cohort study includes adult patients with a new cancer diagnosis. Vaccine administrations for COVID-19 (SARS-CoV-2), influenza, pneumococcal, tetanus/diphtheria/pertussis (TDaP), herpes zoster (RZV), human papillomavirus (HPV), and hepatitis B (hepB) were assessed. The primary outcome was complete vaccine adherence. Results: Two hundred and eighty-three oncology patients were included. The median age at diagnosis was 63 years old, and most subjects were females (60%). The two most common malignancies were gastrointestinal and breast cancer at 26.5% and 15.2%, respectively. Suboptimal vaccine adherence rates were observed across the entire oncology population. Complete adherence was observed in only 1.4% of patients. Vaccine specific adherence rates were as follows, SARS-CoV-2: 38.9%; influenza: 11.4%; pneumococcal: 12.7%; TDaP: 13.1%; RZV: 3.5%; HPV: 0%; and hepB: 34%. Among the vaccine schedules assessed, SARS-CoV-2 vaccination rates were the highest with 38.9% of patients being fully adherent and 73% receiving at least one dose. Conclusion: Lower vaccine adherence rates were observed in oncology patients compared to currently published rates. Providers and pharmacists can play a role in assessing and counseling patients on the importance of vaccine adherence before chemotherapy is initiated and after a remission is obtained. [ABSTRACT FROM AUTHOR]

Aims: To systematically review and integrate qualitative‐research results pertaining to psychological distress in patients with breast cancer and to clarify its causes and drivers. Background: Patients with breast cancer experience psychological distress in the stages of diagnosis, treatment, and rehabilitation, which seriously affects their quality of life. Through comprehensive qualitative research, the study comprehensively describes the experiences of patients with breast cancer to guide medical personnel in taking better care of them. Design: A systematic review and synthesis of qualitative studies. Methods: Qualitative studies were included if they were related to the psychological‐distress experiences of patients with breast cancer. The Joanna Briggs Institute Qualitative Assessment and Review Instrument was used to appraise study quality. Data were synthesised using the Thomas and Harden method of thematic and content analysis. Data Sources: Nine electronic databases (PubMed, Embase, Cochrane Library, CINAL [via EBSCO], and PsycINFO, China Knowledge Resource Integrated Database, Wanfang, Chinese Biomedical, and Weipu) were searched from inception until February 2024. Results: Thirteen studies were included in the meta‐synthesis. Four analytical themes were identified: diagnostic and therapeutic, individual, environmental, and interpersonal factors. Conclusions: Psychological distress is a subjective feeling influenced by interactions among individual, therapeutic, environmental, and interpersonal factors, and it is commonly encountered among patients with breast cancer. Therefore, to optimise the management of psychological distress, the characteristics and external environment of patients with breast cancer should be carefully considered when delivering routine nursing care. Impact: Patients experience psychological distress at different stages of breast cancer; however, the causes of psychological distress at different stages differ. Medical staff should implement targeted psychological‐distress intervention measures based on factors relevant to different stages. Reporting Method: The Enhancing Transparency in Reporting the Synthesis of Qualitative Research statement. Registration: The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023417364). [ABSTRACT FROM AUTHOR]

Background: Breast cancer patients experience various adverse symptoms during adjuvant chemotherapy. These adverse symptoms often form symptom clusters and have a negative impact on patients. Aims: To summarise common symptom clusters in different dimensions and their longitudinal changes among breast cancer patients receiving adjuvant chemotherapy. Design: A systematic review. Data Sources: Ten electronic databases were searched from 2001 to January 2024, and the search was last updated on 16 August 2024. Methods: Two reviewers independently assessed the eligibility of each study and extracted data. The Standard Quality Assessment Criteria for Evaluating Primary Research Papers was used to evaluate the quality of included studies. The findings were synthesised narratively. This systematic review has been registered (CRD42022370210). Results: Nine studies with a total of 1454 participants were included. The common symptom clusters in breast cancer patients receiving adjuvant chemotherapy were the gastrointestinal symptom cluster (nausea‐lack of appetite), the fatigue‐pain‐sleep disturbance symptom cluster and the psychological symptom cluster (worry‐sadness‐nervousness‐distress‐feeling irritable‐difficult concentrating). The severity dimension was the most frequently utilised in identifying symptom clusters, with the number and concurrence of symptom clusters showing variation over time. Conclusions: This study summarised common symptom clusters in breast cancer patients receiving adjuvant chemotherapy and revealed their changes from symptom dimensions and the chemotherapy process. These findings support further exploration of symptom cluster changes and underlying mechanisms, facilitating the design of targeted management strategies, including appropriate interventions and measurement dimensions in clinical nursing, to ultimately reduce patients' symptom burden. Impact: Common symptom clusters have been identified in breast cancer patients receiving adjuvant chemotherapy. Clinical nursing in oncology can prioritise these symptom clusters and provide patients with targeted management strategies. Reporting Methods: PRISMA guidelines and SWiM guidelines. Patient or Public Contribution: No patient or public contribution. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant endocrine therapy has a vital role in reducing breast cancer mortality. The beliefs in adjuvant endocrine therapy is a very important factor in the medication adherence of breast cancer survivors. Therefore, it is necessary to develop a standardized scale for assessment of adjuvant endocrine therapy. The purpose of this study was to identify the attributes of adjuvant endocrine therapy beliefs, and to evaluate adjuvant endocrine therapy beliefs scale psychometric properties. Methods: A hybrid model was applied to identify the concept of adjuvant endocrine therapy beliefs and measurement question were developed by the scale development process. Statistical analysis using validity analysis and Rasch analysis based on item response theory were performed. A total of 228 breast cancer survivors in South Korea participated in the study. Results: The finally developed adjuvant endocrine therapy beliefs scale consisted of 22 items. The items extracted by 4 factors explained 59.72% of the total variance. The model fit showed an acceptable level. The adjuvant endocrine therapy beliefs scale was excellent in convergent and discriminant validity with reliability. Conclusion: This scale is expected to be practical and useful in identifying adjuvant endocrine therapy beliefs and developing intervention strategies to promote adjuvant endocrine therapy adherence. In addition, continuous education and support should be accompanied so that breast cancer survivors can maintain positive beliefs in adjuvant endocrine therapy adherence. [ABSTRACT FROM AUTHOR]

PURPOSE: Assessing risk of recurrence for nonmetastatic triple-negative breast cancer (TNBC) is a key determinant of therapeutic strategy. The best predictor of recurrence risk is failure to achieve a pathologic complete response after preoperative chemotherapy, but it imperfectly correlates with the definitive end points of relapse-free and overall survival (OS). The inability to accurately predict recurrence has led to increasingly toxic treatment regimens for patients with early-stage TNBC. Better assays for recurrence risk are needed to tailor aggressive therapy for patients who need it and avoid overtreatment and unnecessary toxicity for those at low risk. The purpose of this study was to determine if patient-derived xenograft (PDX) engraftment of newly diagnosed breast tumors can serve as an accurate predictor of recurrence and death from breast cancer. METHODS: This study was a blinded noninterventional trial comprising 80 patients with newly diagnosed, nonmetastatic, estrogen receptor (ER)-negative or ER-low breast cancer. RESULTS: PDX engraftment was strongly associated with relapse in 1 year: 8 of 18 (44.4%) patients whose tumors engrafted relapsed versus 1 of 62 (1.6%) patients whose tumors did not engraft (P <.0001). Patients whose tumors engrafted had a hazard ratio (HR) for relapse of 17.5. HRs for OS and breast cancer-specific survival in PDX+ patients were 21.1 and 39.5, respectively. CONCLUSION: We report that the ability of a tumor to engraft as a PDX predicts early recurrence by serving as a functional readout of aggressiveness and prospectively identifies the most devastating tumors. This provides new opportunity to develop surrogate assays, such as biomarkers of engraftment, which will extend the clinical feasibility of this finding. [ABSTRACT FROM AUTHOR]

PURPOSE: At the primary analysis, the APHINITY trial reported a statistically significant but modest benefit of adding pertuzumab to standard adjuvant chemotherapy plus trastuzumab in patients with histologically confirmed human epidermal growth factor receptor 2 (HER2)–positive early-stage breast cancer. This study evaluated whether the 80-gene molecular subtyping signature (80-GS) could identify patients within the APHINITY population who derive the most benefit from dual anti-HER2 therapy. METHODS: In a nested case-control study design of 1,023 patients (matched event to control ratio of 3:1), the 80-GS classified breast tumors into functional luminal type, HER2 type, or basal type. Additionally, 80-GS distinguished tumor subtypes that exhibited a single-dominant functional pathway versus tumors with multiple activated pathways. The primary end point was invasive disease-free survival (IDFS). Hazard ratios (HRs) were evaluated by Cox regression. After excluding patients without appropriate consent and those with missing data, 964 patients were included. RESULTS: The 80-GS classified 50% (n = 479) of tumors as luminal type, 28% (n = 275) as HER2 type, and 22% (n = 209) as basal type. Most luminal-type tumors (86%) displayed a single-activated pathway, whereas 49% of HER2-type and 42% of basal-type tumors were dual activated. There was no significant difference in IDFS among different conventional 80-GS subtypes (single- and dual-activated subtypes combined). However, basal single-subtype tumors were significantly more likely to have an IDFS event (hazard ratio, 1.69 [95% CI, 1.12 to 2.54]) compared with other subtypes. HER2 single-subtype tumors displayed a trend toward greater beneficial effect on the addition of pertuzumab (hazard ratio, 0.56 [95% CI, 0.27 to 1.16]) compared with all other subtypes. CONCLUSION: The 80-GS identified subgroups of histologically confirmed HER2-positive tumors with distinct biological characteristics. Basal single-subtype tumors exhibit an inferior prognosis compared with other subgroups and may be candidates for additional therapeutic strategies. Preliminary results suggest patients with HER2-positive, genomically HER2 single-subtype tumors may particularly benefit from added pertuzumab, which warrants further investigation. Adjuvant pertuzumab benefit prediction by the 80-gene BluePrint signature in the APHINITY (BIG 4-11) trial #BIGNetwork #APHINITYtrial [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignant tumor and a major cause of mortality among women worldwide. Atramacronoid A (AM-A) is a unique natural sesquiterpene lactone isolated from the rhizome of Atractylodes macrocephala Koidz (known as Baizhu in Chinese). Our study demonstrated that AM-A triggers a specific form of cell death resembling PANoptosis-like cell death. Further analysis indicated that AM-A-induced PANoptosis-like cell death is associated with the CASP-3/PARP-GSDMD-MLKL pathways, which are mediated by mitochondrial dysfunction. These results suggest the potential of AM-A as a lead compound and offer insights for the development of therapeutic agents for breast cancer from natural products. [ABSTRACT FROM AUTHOR]

The undescribed phosphatidylcholine (1), along with twelve known compounds, was isolated from the cultures of white rot fungus Microporus xanthropus PP17-20. In this work the fungus was cultivated in Yeast-Malt extract medium to explore active compound production. The chemical structures were elucidated on the basis of spectroscopic and HRESIMS data. Several isolated compounds were evaluated for anti-proliferative activity against A549 and MCF-7 cancer cell lines. [ABSTRACT FROM AUTHOR]

National screening programs for gastric, colorectal, lung, breast, and cervical cancers are offered in Japan. The initial introduction of cancer screening programs was decided based on experts' opinions. Since 2003, the research groups funded by the National Cancer Center have published screening guidelines for gastric, colorectal, lung, prostate, cervical, and breast cancers. Although such guidelines have increasingly contributed to promoting evidence-based screening, it is still insufficient. Cancer screenings have mainly been provided in communities and workplaces. Compared with the average of OECD countries, participation rates in breast and cervical cancer screening are lower. Participation rates cannot be accurately calculated due to a lack of comprehensive cancer screening registries at the national level. Alternatively, estimates are derived from questionnaire surveys conducted on randomly selected samples from the national population. The quality assurance system has been limited to community-based screening and was not adapted to workplace screening until 2018. While there is a long history of cancer screening, the complex program delivery system might be a barrier to increasing the participation rate. Continued efforts are necessary to offer evidence-based cancer screening and establish an effective quality assurance system. [ABSTRACT FROM AUTHOR]

Objective: To analyze differences between screen-detected and non-screen-detected invasive breast cancers by tumour characteristics and age at diagnosis in the nationwide population-based mammography screening program in Sweden. Methods: Data were retrieved from the National Quality Register for Breast Cancer for 2008–2017. Logistic regression analysis was used to estimate the likelihood for a tumour to be screen-detected by tumour characteristics and age group at diagnosis. Results: In total there were 51,429 invasive breast cancers in the target age group for mammography screening of 40–74 years. Likelihood of screen detection decreased with larger tumour size, lymph node metastases, higher histological grade and distant metastasis. Odds ratios (ORs) for negative oestrogen (ER) and progesterone (PgR) were 0.41 and 0.57; for positive HER2, 0.62; for Ki-67 high versus low, 0.49. Molecular sub-types had OR of 0.56, 0.40 and 0.28, respectively, for luminal B-like, HER2-positive and triple negative versus luminal A-like. Adjusting for tumour size (T), lymph node status (N), age, year and county at diagnosis slightly elevated the ORs. Statistically significant interactions between tumour characteristics and age were found (p < 0.05) except for ER and PgR. The age group 40–49 deviated most from the other age groups. Conclusions: Our study demonstrates that screen-detected invasive breast cancers had more favourable tumour characteristics than non-screen-detected after adjusting for age, year and county of diagnosis, and even after adjusting for T and N. The trend towards favourable tumour characteristics was less pronounced in the 40–49 age group compared to the other age groups, except for ER and PgR. [ABSTRACT FROM AUTHOR]

Background: Inconclusive epidemiological evidence suggests that diet quality indices may influence breast cancer (BC) risk; however, the evidence does not consider the molecular expression of this cancer. Purpose: We aimed to evaluate if diet quality is related to molecular subtypes of BC, in women residing in Northern Mexico. Methods: This is a secondary analysis of 1,045 incident cases and 1,030 population controls from a previous case-control study, conducted between 2007 and 2011 in Northern Mexico. Information about the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) was obtained from medical records to classify BC as luminal (ER + and/or PR+/HER2–), HER2+ (ER+/–and/or PR+/–/HER2+), or triple-negative (TN) (ER– and PR–/HER2–) cases. Food consumption was assessed with a semi-quantitative food frequency questionnaire. Diet quality was evaluated using the Mexican Diet Quality Index (MxDQI) and the Mexican Alternative Healthy Eating Index (MxAHEI). We used unconditional logistic regression models to estimate the association between Mexican diet quality indices and BC molecular subtypes. Results: The MxDQI was related to lower odds of BC (ORT3vsT1=0.24; 95%CI: 0.18, 0.31). Similarly, MxAHEI was negatively associated with BC (ORT3vsT1=0.43; 95%CI: 0.34, 0.54). The associations of both indices remained significant in the ER + and ER- tumors, and in the BC luminal and HER2 + molecular subtypes, except in the TN molecular subtype for MxAHEI, which was not statistically significant. Conclusions: Our findings showed that MxDQI and MxAHEI were negatively associated with BC risk regardless of its molecular subtype. [ABSTRACT FROM AUTHOR]

Multiple intervention strategies have been found effective for increasing physical activity among breast cancer survivors, yet most breast cancer survivors fail to meet physical activity recommendations. Optimization of interventions can facilitate real word implementation to ensure effective and efficient intervention delivery. Using a full-factorial design based on the Multiphase Optimization Strategy, 337 breast cancer survivors were randomized to receive a combination of four intervention components: (1) supervised exercise sessions, (2) facility membership, (3) Active Living Every Day (ALED), and (4) Fitbit. Moderate-to vigorous (MVPA) and light-intensity physical activity (LPA) were measured at baseline, 3 months, and 6 months with a hip-worn Actigraph GT3X+. Normal linear mixed models with separate intercepts for each subject were fit in the SAS 9.4 Mixed procedure. Participants who received supervised exercise sessions engaged in more MVPA, 153.58 min/week vs. 133.0 min/week (F = 3.97, p = 0.048) and LPA, 170.26 min/day versus 160.98 light PA minutes/day (F = 4.67, p = 0.032), compared to participants who did not receive supervised exercise. The effects of the three other intervention components on MVPA were not significant; however, those that received ALED engaged in less LPA (F = 6.6, p = 0.011). Supervised exercise sessions resulted in significant increases in MVPA and LPA in a sample of breast cancer survivors. Of note, these sessions were provided only during the first 6 weeks of the intervention and effects remained significant at 6 months. Results of this trial could inform future implementation efforts to ensure effective and efficient delivery of physical activity programs for breast cancer survivors. [ABSTRACT FROM AUTHOR]

Following treatment, cancer survivors often experience pain that negatively impacts their quality of life. Although both anxiety and fear of cancer recurrence (FCR) have been shown to exacerbate pain interference, less is known about either the temporal relationship between anxiety/FCR and pain interference or modifiable cognitive/emotional factors that might moderate that relationship among cancer survivors. This longitudinal study aims to advance our understanding of the impact of both anxiety and FCR following primary cancer treatment on subsequent pain interference. We also examined potentially modifiable moderators (i.e., cancer-related illness beliefs and emotion regulation difficulties) of the relationship between anxiety/FCR and subsequent pain interference. Adults (N = 397; 67% female; Mage = 59.1 years) diagnosed with breast, colorectal, or prostate cancer completed self-report measures at baseline (average of 2.5 months following treatment completion) and at 6-month follow-up. Both greater anxiety and FCR not only predicted subsequent pain interference, but also predicted increases in pain interference over time. Additionally, complex interaction patterns were observed between anxiety and the potential moderators on pain interference. Specifically, lower Personal Control beliefs and higher Consequences beliefs were associated with greater pain interference for those with lower levels of anxiety/FCR. Emotion regulation difficulties also moderated the anxiety-pain interference link (i.e., was more strongly associated with greater pain interference at lower levels of anxiety), but not the FCR-pain link. Chronicity beliefs did not interact with anxiety or FCR in predicting pain interference. This study advances our understanding of the role of anxiety/FCR on pain interference over time as well as potential psychological treatment targets for individuals at greater risk for longer-term pain following cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Women who receive a breast cancer diagnosis often have to cope with physical and psychological issues, even some years after diagnosis and treatments. Physical changes and negative inner sensations damage body image, leading to reduced contact with the body and social relationships due to shame and increased fear of cancer recurrence. Several psychological interventions have been conducted to manage psycho‐emotional issues involving bodily sensations and emotions. Aims: This study aimed to propose a virtual reality (VR) intervention to improve awareness and management of bodily sensations. Materials and Methods: Thirteen women participated in a study design in which they were guided to focus their attention on three different parts of their body (i.e. arms, chest and legs) in a randomised way. Participants followed a light as a virtual visual stimulation and heard the researcher's voice. Results: Findings showed that physical discomfort and negative emotions related to the body significantly decreased after the VR intervention. Additionally, the present VR intervention decreased anxiety. Accordingly, women qualitatively stated being satisfied with the intervention, considering VR as a helpful tool to be more focused on their inner sensations and decrease discomfort. Discussion: In conclusion, VR may be implemented to promote bodily awareness in women with a breast cancer diagnosis, improving bodily awareness and the management of negative emotions. Conclusion: Directions for future research and clinical implications are given. [ABSTRACT FROM AUTHOR]

Purpose: Breast cancer (BC) is the most frequently diagnosed cancer among women. Approximately 40% of BC survivors are diagnosed during the peak years of their professional career. Women face numerous obstacles when returning to work (RTW) after BC. Their decision-making process and self-efficacy to overcome these barriers may undergo alterations. The objective of this study was to validate the Return-to-work Obstacles and Self-Efficacy Scale (ROSES) for BC survivors, with a focus on three psychometric properties: construct validity, test–retest reliability, and predictive validity. Methods: This prospective study consists of three phases: Phase 1 (baseline, during sick leave) was conducted to evaluate construct validity, Phase 2 (2 weeks later) assessed test–retest reliability, and Phase 3 (6-month follow-up, RTW or not) aimed to evaluate predictive validity. A total of 153 BC survivors participated in Phase 1 of the study, where they completed the 10 dimensions of the ROSES (e.g., fear of relapse, cognitive difficulties). Confirmatory factor analyses (CFA), Pearson correlations, and Cox regressions were performed, with respect to each phase. Results: The mean duration for RTW with the same employer was 62.7 weeks. CFAs confirmed the ROSES structure, which had previously been established for other health conditions, showing satisfactory coefficients. Significant Pearson correlation coefficients were observed between the ROSES dimensions from Phase 1 to Phase 2, ranging from 0.66 to 0.88. When considering various confounding variables, chemotherapy treatment and cognitive difficulties (ROSES dimension) emerged as the only significant predictors of RTW. Conclusion: These findings support the utilization of the ROSES in clinical and research settings for BC survivors to improve their successful RTW. After an initial screening using the ROSES, occupational health professionals can further conduct a focused and thorough evaluation of specific dimensions, such as cognitive difficulties. Additional research and information are required to assist BC survivors in dealing with cognitive impairments induced by chemotherapy when they return to work. [ABSTRACT FROM AUTHOR]

In patients with right-sided breast cancer the liver can be partially irradiated during adjuvant radiotherapy (RT). We aimed to determine breast cancer RT effects on liver using with magnetic resonance elastography (MRE) and biological results. This retrospective study enrolled 34 patients diagnosed with right-sided breast cancer who underwent adjuvant RT. Liver segment assessments were conducted using MRE for all participants. Additionally, a complete blood count and liver enzyme analysis were performed for each patient. All measurements were taken both prior to the initiation and upon completion of RT. A statistically significant difference was found in ALT (p = 0.015), ALP (p = 0.026), total protein (p = 0.037), and albumin (p = 0.004) levels before and after RT. The highest mean liver stiffness (kPa) value was recorded in segment 8, while the lowest was observed in segment 6. A weak but statistically significant positive correlation was found between segment 5 stiffness and liver volume (p = 0.039). Additionally, a statistically significant positive correlation was detected between ALP levels and the stiffness values in segment 4A (p = 0.020) and segment 6 (p = 0.003). Conversely, a weak negative correlation was observed between the stiffness values in segment 8 and post-RT total protein levels (p = 0.031). MRE can help us identify the level of fibrotic stiffness in the liver segments within the RT area without establishing clinical symptoms. MRE can support the clinician in evaluating the liver functions of right breast cancer patients who underwent RT. We assume these results will facilitate new studies with a large number of patients on MRE imaging at certain intervals in the follow-up of patients with right breast cancer who received RT before the development of radiation-induced liver disease (RILD). [ABSTRACT FROM AUTHOR]

Introduction: Sacituzumab govitecan (SG) is approved for patients with previously treated metastatic or locally advanced triple-negative breast cancer (TNBC), as per the ASCENT trial results. Real-world studies (RWSs) cover more diverse patients than clinical trials, offering crucial data for healthcare policies. This study aimed to investigate the safety and efficacy of SG in real-world Polish patients with previously treated metastatic TNBC. Methods: In this ambispective multicenter cohort study, we collected demographic and clinical data. Premedication, adjustments in SG dosage, and treatment regimen adhered to the product's characteristics. Results: We included 79 female patients. The median age at SG initiation was 53 years; 32% of patients were initially diagnosed with a non-TNBC subtype. The median number of previous palliative lines was 2. Seven patients presented with brain metastases. The median overall survival was 10.3 months, and the median progression-free survival (PFS) was 4.4 months. The overall response rate was 35%, with a median time to response of 2 months. SG was discontinued by 70% of patients, primarily due to disease progression (95%). Treatment delays due to adverse events (AEs) occurred in 67% and dose reductions in 25% of patients, with neutropenia being the most common. Grade ≥ 2 AEs included neutropenia (43%), anemia (10.1%), and diarrhea (4%). A longer interval between breast cancer diagnosis and SG initiation or between metastasis diagnosis and SG initiation correlated with improved PFS, likely reflecting the disease's biological aggressiveness rather than treatment efficacy. Conclusion: In this RWS, SG demonstrated effectiveness and safety in patients with previously treated metastatic TNBC, consistent with ASCENT trial outcomes. Further research is needed to explore the efficacy of SG in different patient populations and healthcare systems. [ABSTRACT FROM AUTHOR]

Breast and gynecologic cancers are common across the world and are associated with substantial societal and economic burden. Pembrolizumab was among the first immune checkpoint inhibitors targeting programmed cell death protein 1 to be approved for the treatment of patients with triple-negative breast cancer, cervical cancer, and endometrial cancer. Recent clinical trials have established pembrolizumab regimens as a standard of care treatment for these tumor types. Clinical data are further supported by patient-reported outcome, cost-effectiveness, and real-world evidence. Pembrolizumab monotherapy and combination regimens do not negatively influence health-related quality of life and are cost-effective relative to comparators. Ongoing phase 3 studies with pembrolizumab will expand the current understanding of its use in breast and gynecologic cancers. Several of these studies are in patients with early-stage disease with the hope of curing patients. The main objective of this review is to summarize the clinical, humanistic, and economic value of pembrolizumab in these settings and to describe the future challenges for patients, caregivers, clinicians, and payers. [ABSTRACT FROM AUTHOR]

Objective: To investigate the therapeutic effect of Sanhuang Xiexin Decoction (SXD) on triple-negative breast cancer (TNBC) in mice and its underlying mechanism. Methods: The high-performance liquid chromatography (HPLC) was used to quantitate and qualify SXD. A total of 15 female BALB/c mice were inoculated subcutaneously on the right hypogastrium with 3×105 of 4T1-Luc cells to establish TNBC mouse model. All mice were divided randomly into 3 groups, including phosphate buffered solution (PBS), SXD and doxorubicin (DOX) groups (positive drug). Additionally, tumor growth, pathological changes, serum lipid profiles, expression of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway and its key targets including inflammatory factors, cell cycle and epithelial-mesenchymal transition (EMT) markers were investigated. Besides, the biosafety of SXD was also evaluated in mice. Results: Rhein, coptisine, berberine hydrochloride and baicalin were all found in SXD, and the concentrations of these 4 components were 0.57, 2.61, 2.93, and 46.04 mg/g, respectively. The mouse experiment showed that SXD could notably suppress the development of tumors and reduce the density of tumor cells (P<0.01). The serum lipid analysis and Oil-Red-O staining both showed the differences, SXD group exhibited higher serum adiponectin and HDL-C levels with lower TC and LDL-C levels compared to the PBS and DOX groups (P<0.05 or P<0.01), respectively. SXD also decreased the levels of phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3) expressions and its downstream factors, including mostly inflammatory cytokine, EMT markers, S phase of tumor cells and vascular endothelial growth factor (VEGF) expression (P<0.05 or P<0.01), respectively. The biosafety assessment of SXD revealed low levels of toxicity in mice. Conclusion: SXD could inhibit TNBC by suppressing JAK2-STAT3 phosphorylation which may be associated with modulation of lipid metabolism. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BRCA), the hormone related malignant tumor, is well-known for poor prognosis. ZNF208 mainly acts as a transcription factor in various tumors, and the single nucleotide polymorphisms (SNPs) of ZNF208 are related to telomere length. Nevertheless, its role in breast tumorigenesis is largely unknown. Methods: We systematically investigated the gene expression, prognostic value, and promoter methylation of ZNF208 in BRCA with Gene Expression Profiling Interactive Analysis (GEPIA) and DNA Methylation Interactive Visualization Database (DNMIVD). Meanwhile, we clarified the association of ZNF208 with tumor-infiltrating immune cells (TICs) from Tumor Immune Estimation Resource (TIMER). Furthermore, we determined the biological process and functional enrichment from Cancer single-cell state atlas (CancerSEA). Finally, we verified our results with prognostic analysis and immunohistochemistry (IHC) assay. Results: We discovered that ZNF208 was downregulated in breast cancer, and low expression of ZNF208 predicted worse prognosis of BRCA patients. The promoter methylation level of ZNF208 was obviously increased, and ZNF208 was associated with TlCs in BRCA. In addition, ZNF208 could inhibit the metastasis and invasion biological processes, and regulate the MAPK and RAS signaling pathways in BRCA. Conclusion: Our findings illustrate that ZNF208 can function as a tumor suppressor and predict prognosis of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Breast cancer remains the most common invasive cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Trastuzumab (Tz) is typically used to treat HER2-positive breast cancers, but its potential in TNBC is unclear. Objectives: To investigate the effects of trastuzumab on cell viability, apoptosis, cell cycle progression, and gene expression in TNBC cell lines compared with HER2-positive and normal cell lines. Design: This is an in vitro experimental pre-clinical study using cultured cancer cell lines. Methods: MDA-MB-231 and 4T1 (TNBC), MCF-7 (HER2 -positive), and HSF (normal) cell lines were treated with 20 μg/mL trastuzumab for 24 hours. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis by flow cytometry, cell cycle progression by DNA content analysis, and gene expression by qPCR. Results: Trastuzumab significantly reduced cell viability and induced apoptosis in TNBC cell lines, comparable to effects in HER2-positive MCF-7 cells. Cell cycle analysis revealed G2/M phase arrest in TNBC cells. Gene expression analysis showed upregulation of ERBB2, NOTCH1, EGFR, PIK3CA, and PTEN in MDA-MB-231 cells, while 4T1 cells exhibited downregulation of most genes except NOTCH1. Conclusion: This study provides initial evidence for trastuzumab's potential therapeutic effects in TNBC, despite low HER2 expression. The observed cytotoxicity, apoptosis induction, and cell cycle modulation in TNBC cells warrant further investigation into trastuzumab's mechanisms of action in HER2 -negative contexts and its potential repurposing for TNBC treatment. [ABSTRACT FROM AUTHOR]

Background: Since ancient times many traditional medicine systems around the world have been using different parts of Annona muricata L. (AM), to treat cancer. Indeed, numerous in vitro and in vivo studies also have shown anticancer properties of different solvent extracts of different parts of AM. Even the same part of the plant has shown different levels of anticancer properties based on geographical variations. Therefore, in the present study, the anticancer potential of the leaves, fruit pulp and the fruit peel of the AM that is grown in Sri Lanka was comparatively analyzed with the intention of identifying the most suitable part to be developed into a nutraceutical with anticancer effects. Methods: Freeze-dried aqueous extracts of immature leaves (ILAM), mature leaves (MLAM), pulp (PAM) and peel (PLAM) of AM were analyzed for their antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and 2,2-azinobis-3-ethylbenzothiozoline-6-sulfonic acid (ABTS) cation decolorization assays. Their cytotoxicity on breast cancer (MCF-7) cells, colorectal adenocarcinoma (DLD-1) cells and normal human gingival fibroblasts (HGF-1) were determined by the 3-(4,5- dimethylthiazole-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) assay. Their effect on mRNA expression of proapoptotic (Bax and caspase-7) and cell cycle arresting (p21) genes was analyzed by RT- qPCR in the same cell lines. Results: ILAM demonstrated the highest antioxidant activity in both DPPH and ABTS assays followed by MLAM, PLAM and PAM. In the MTT assay, both ILAM and MLAM demonstrated strong cytotoxic activity against MCF-7 and DLD-1 cell lines while there were no cytotoxic effects on the normal human cell line HGF-1. Both ILAM and MLAM demonstrated concentration-dependent upregulation of mRNA expression of cell cycle arresting gene p21 and apoptosis inducing genes Bax and caspase-7 in MCF-7 and DLD-1 cells. Conclusion: The AEAM leaves grown in Sri Lanka has significantly higher antioxidant activity as well as selective cytotoxic effects on MCF-7 and DLD-1 cancer cells compared to its PL and P counterparts. Further, the AEAM leaves induced mRNA expression of the anticancer genes p21, Bax and caspase-7, indicating its potential to be developed into an anticancer drug against breast and colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: HER2-targeting therapies may increase the risk of decreased left ventricular ejection fraction (LVEF), potentially leading to heart failure. The growing number of breast cancer survivors due to HER2-targeted treatments necessitates long-term cardiotoxicity management. Method: This retrospective study included HER2-positive breast cancer patients aged 18 or older who received at least 1 dose of HER2-targeting treatment between 2016 and 2020. The primary endpoint was the incidence of cardiotoxicity, defined as LVEF <50% with a 10% decline, LVEF drop by >15%, or onset of symptomatic heart failure. Secondary endpoints included the proportion of patients with baseline LVEF 50% to 55% developing cardiotoxicity, those discontinuing HER2 therapy due to heart failure, those treated with heart failure medications, and those continuing HER2 therapy while on heart failure medications. Another secondary outcome was the development of a hospital protocol for monitoring cardiotoxicity in these patients. Results: A total of 212 patients were included, with a median age of 56.5 years (interquartile range: 43-58 years). Twenty-two patients (10.37%) experienced cardiotoxicity from HER2-targeted treatment. Thirteen patients (6.13%) had asymptomatic heart failure with LVEF decrease of more than 10% to less than 50%. Five patients (2.35%) with LVEF less than 40% had asymptomatic heart failure, while 4 patients (1.88%) had symptomatic heart failure regardless of LVEF decline. HER2-targeted treatment was temporarily discontinued in 3 (13.63%) patients and permanently in 4 (18.18%) patients due to cardiotoxicity. The remaining 15 patients resumed treatment without interruption. Only 13 out of 22 patients were referred to cardiologists and prescribed heart failure medications. Conclusion: Close monitoring of LVEF in patients receiving HER2-targeting therapy can help health care providers initiate anti-heart failure medications to prevent LVEF deterioration and maintain HER2-targeting therapy. [ABSTRACT FROM AUTHOR]

Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, is crucial in treating hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic or recurrent breast cancer. However, its association with drug-induced interstitial lung disease (DI-ILD) is concerning. We present an 82-year-old woman with breast cancer receiving abemaciclib, who developed persistent cough and malaise. Initial diagnostics suggested pneumonia, supported by ground-glass opacities and consolidations on chest high-resolution computed tomography. Suspecting DI-ILD, a transbronchial lung cryobiopsy (TBLC) was performed, revealing fibrosing organizing pneumonia and confirming abemaciclib-induced ILD. Discontinuing abemaciclib led to significant symptom improvement, supporting the diagnosis. This case report describes the clinical presentation and diagnostic approach in a patient with suspected abemaciclib-induced ILD, including the use. To our knowledge, this is the first reported case of fibrosing organizing pneumonia as a histopathological pattern in abemaciclib-induced ILD, expanding knowledge of this therapy's pulmonary adverse events. Histopathological features included diffuse lymphocytic infiltration, polypoid intra-alveolar fibrosis, intraluminal granulation tissue plugs with dense hyalinization, hyalinized fibrotic alveolar septa lesions, and obliterative fibrotic processes affecting alveolar ducts. Our case suggests that TBLC might be useful in recognizing DI-ILD by providing detailed lung tissue examination, which can facilitate early diagnosis and guide management. Identifying fibrosing organizing pneumonia indicated a potentially corticosteroid-responsive pathology, suggesting a more favorable prognosis compared with patterns like diffuse alveolar damage. This case highlights the potential for abemaciclib-induced ILD to occur even after prolonged treatment periods, emphasizing the importance of vigilance and consideration of diagnostic intervention for patients on cyclin-dependent kinase 4/6 inhibitors presenting with respiratory symptoms. Timely recognition and appropriate management may mitigate adverse outcomes. Further studies are needed to confirm these findings and to better understand the role of TBLC and histopathological examination in diagnosing and managing abemaciclib-induced ILD. [ABSTRACT FROM AUTHOR]

Background: Breast cancer poses a significant public health challenge in Tanzania. Limited knowledge about breast cancer and negative attitudes toward screening practices contributes to delayed diagnoses and poorer patient outcomes. Catholic nuns, who are often nulliparous, represent a population with an increased risk of developing breast cancer. Despite this risk, they remain an understudied group regarding breast cancer awareness and screening practices. Objective: This study aimed to assess breast cancer knowledge and attitudes toward screening practices among Catholic nuns residing in Tanzania's Lake Zone. Study design: The study was a cross-sectional design. Methods: A total of 385 Catholic nuns participated in the study. To ensure a representative sample, nuns were chosen through simple random sampling, giving each Catholic nun an equal probability of being selected. Data were collected using a self-administered questionnaire and then analyzed using STATA version 18.0. Both descriptive and inferential statistics were used to draw conclusions. In inferential statistics, logistic regression was used to test for associations between categorical variables. The test statistics were considered significant when the P -value was less than.05 at a 95% confidence interval (CI). Results: This study enrolled 385 catholic nuns. 57.1% (95% CI, 52.0%-62.1%) of all surveyed catholic nuns had inadequate knowledge of breast cancer. Misconceptions also emerged as significant risk factors for inadequate knowledge. Thus, lack of awareness of breast cancer risk factors increased the odds by 5.57 times (adjusted odds ratio [AOR]: 5.57; 95% CI: 2.84-10.92; P <.001). In addition, believing cancer was not inheritable (AOR: 2.65; 95% CI: 1.14-6.15; P =.024), misperceiving oneself as being in a low-risk group (AOR: 1.65; 95% CI: 1.03-2.66; P =.039), and underestimating the vulnerable age group (believing it is not above 40 years) (AOR: 2.60; 95% CI: 1.49-4.51; P =.001) were all significantly associated with higher odds of inadequate knowledge. Regarding the attitude toward breast cancer screening practices, 62.3% (95% CI, 57.3%-67.2%) of the catholic nuns had negative attitudes. Conclusion: These findings highlight the need for breast health intervention educational programs to improve breast cancer awareness among Catholic nuns. Such programs should address risk factors, symptoms, screening methods, and treatment options, dispelling misconceptions. By empowering nuns with knowledge, they can make informed decisions about their health and take charge of their well-being. [ABSTRACT FROM AUTHOR]

Gold nanoparticles (NPs) are promising for cancer therapy due to their versatile shapes, optical properties, adjustable sizes, and facile functionalization. However, their diverse physicochemical properties, complex in vivo environments, and cellular heterogeneity lead to markedly different interactions with cells, impacting reproducibility and application selection. To address this, we implemented a DNA barcoding system to label gold NPs with varying shapes, sizes, and surface modifications for tumor delivery optimization. Six NP species, comprising three shapes (sphere, rod, triangle) and two sizes (40 nm, 80 nm), were tagged with unique DNA barcodes. Barcodes demonstrated minimal detachment, no interference with cell interactions, and resistance to DNase digestion. Next‐generation sequencing revealed that sphere NPs exhibited poor in vitro uptake but superior in vivo tumor targeting, likely due to enhanced endothelial interactions and reduced macrophage clearance. Additionally, 80 nm nanotriangles displayed excellent tumor targeting both in vitro and in vivo. Supporting experiments validated these findings. To demonstrate practical utility, the NPs were applied in siRNA delivery and photothermal therapy in a breast tumor model. This study pioneers the integration of DNA barcoding with gold NPs to systematically explore shape, size, and surface modifications for in vivo delivery. [ABSTRACT FROM AUTHOR]

Cancer diagnostic probe (CDP) as a newly entered tool in real-time breast cavity margin evaluation showed great improvement in smart margin shaving intra-operatively. This system increased the rate of involved margin detection to 30% with respect to frozen section. In this study for the first time we showed the independent role of CDP in finding the involved cavity side margins which were not diagnosed by permananet pathology of their tumor side interface. Among 147 detected margins by CDP, 23 lesions with invasive component and ductal carcinoma in-situ/ductal cancerization weren't reported as involved margins in permanent pathology of tumor side. Our gold standard was the histology of cavity margin specimen had been scored as involved lesion by CDP. It seems that even when the permanent pathology of surgical margins is used for final declaration, role of CDP is irreplaceable. This distinguished achievement has been obtained intra-operatively in real-time by CDP while involved report in permanent pathology of tumor margins induce re-surgery for the patient. [ABSTRACT FROM AUTHOR]

Background: Previous observational research has indicated a correlation between Parkinson's disease (PD) and multiple cancers; but the causality remains unclear. Thus, we utilized Mendelian randomization (MR) analysis to explore the potential causal link between PD and various cancers. Methods: We conducted a bidirectional two-sample Mendelian randomization (TSMR) of genetic variants associated with PD and 14 types of cancers. Summary statistics on PD and 14 types of cancers were obtained from the International Parkinson's Disease Genomics Consortium and the study by Sakaue et al. The primary method employed was inverse variance weighted (IVW), complemented by multiple sensitivity analyses to evaluate heterogeneity and pleiotropy. The false discovery rate (FDR) was employed to control the false positive rate of multiple hypothesis testing. Results: Following rigorous sensitivity analyses and corrections, our findings revealed suggestive associations between PD and certain cancers. We observed that PD decreases the risk of gastric cancer and colorectal cancer (OR = 0.936, 95% CI = 0.881–0.995, p = 0.034, P FDR = 0.239; OR = 0.955, 95% CI = 0.912–0.999, p = 0.046, P FDR = 0.215), while increasing the risk of breast cancer (OR = 1.043, 95% CI = 1.004–1.084, p = 0.029, P FDR = 0.402). Notably, we found no evidence supporting a reverse causal relationship. Additionally, in the reverse pathway, skin cancer demonstrated a suggestive causal relationship with PD (OR = 0.913, 95% CI = 0.857–0.973, p = 0.005, P FDR = 0.066). Conclusion: Our MR analysis provides evidence supporting unidirectional suggestive causal relationships between PD and certain cancers. These findings enrich our comprehension of the intricate interplay between PD and cancer, warranting further investigation into the underlying biological mechanisms. [ABSTRACT FROM AUTHOR]

Background: Inter- and intra-tumor heterogeneity is considered a significant factor contributing to the development of endocrine resistance in breast cancer. Recent advances in single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) allow us to explore inter- and intra-tumor heterogeneity at single-cell resolution. However, such integrated single-cell analysis has not yet been demonstrated to characterize the transcriptome and chromatin accessibility in breast cancer endocrine resistance. Methods: In this study, we conducted an integrated analysis combining scRNA-seq and scATAC-seq on more than 80,000 breast tissue cells from two normal tissues (NTs), three primary tumors (PTs), and three tamoxifen-treated recurrent tumors (RTs). A variety of cell types among breast tumor tissues were identified, PT- and RT-specific cancer cell states (CSs) were defined, and a heterogeneity-guided core signature (HCS) was derived through such integrated analysis. Functional experiments were performed to validate the oncogenic role of BMP7, a key gene within the core signature. Results: We observed a striking level of cell-to-cell heterogeneity among six tumor tissues and delineated the primary to recurrent tumor progression, underscoring the significance of these single-cell level tumor cell clusters classified from scRNA-seq data. We defined nine CSs, including five PT-specific, three RT-specific, and one PT-RT-shared CSs, and identified distinct open chromatin regions of CSs, as well as a HCS of 137 genes. In addition, we predicted specific transcription factors (TFs) associated with the core signature and novel biological/metabolism pathways that mediate the communications between CSs and the tumor microenvironment (TME). We finally demonstrated that BMP7 plays an oncogenic role in tamoxifen-resistant breast cancer cells through modulating MAPK signaling pathways. Conclusions: Our integrated single-cell analysis provides a comprehensive understanding of the tumor heterogeneity in tamoxifen resistance. We envision this integrated single-cell epigenomic and transcriptomic measure will become a powerful approach to unravel how epigenetic factors and the tumor microenvironment govern the development of tumor heterogeneity and to uncover potential therapeutic targets that circumvent heterogeneity-related failures. [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) helps promote wound healing, but it is unclear whether it stimulates breast cancer cell proliferation, which restricts its application in breast cancer patients. This article explored the effect of PRP on breast cancer cell proliferation through preclinical experiments. Method: We cultivated MDA-MB-231 breast cancer cells with PRP in vitro. Subsequently, we employed Cell Counting Kit-8 (CCK-8) assays to assess their proliferation ability, wound healing assays to evaluate their migration ability, and Transwell assays to detect their invasion ability. Mouse breast cancer 4T1 cells were subcutaneously inoculated into nude mice. After tumor formation, PRP was injected around each tumor. Tumor size was measured. After 15 days, the tumors were surgically removed. Immunohistochemistry was used to detect key proteins involved in proliferation and apoptosis. Results: PRP inhibited the proliferation, migration, and invasion of MDA-MB-231 in vitro. After PRP was injected around tumors in nude mice, tumor growth slowed, Ki67 and phospho-histone H3 (pHH3) expression decreased, and Caspase 3 and Poly (adenosine diphosphate-ribose) polymerase 1 (PARP1) expression increased. Conclusion: The PRP inhibits the proliferation of breast cancer MDA-MB-231 and 4T1 cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Anthracycline chemotherapy is essential in treating breast cancer, yet it can lead to heart damage, particularly affecting the left ventricle. Less is known about its impact on the right ventricle. This meta-analysis examines how anthracyclines may cause subclinical damage to the right ventricle in breast cancer patients, as shown by both advanced strain parameters and traditional echocardiographic measures. Analyzing data from 15 studies and nearly 1200 patients, we found significant declines in right ventricular function post-treatment. Interestingly, this subclinical dysfunction does not appear linked to left ventricle damage or to higher chemotherapy doses, suggesting a unique mechanism for right ventricular impairment. These insights underscore the potential benefit of monitoring RV function in patients undergoing anthracycline treatment, as early detection may lead to improved patient care. Aim: This meta-analysis aims to evaluate the impact of anthracycline chemotherapy on subclinical right ventricular (RV) dysfunction in breast cancer patients, using traditional echocardiographic parameters and strain-based measures, such as the RV global longitudinal strain (RV GLS) and the RV free-wall longitudinal strain (RV FWLS). Methods and Results: A systematic search was conducted according to PRISMA guidelines, including 15 studies with a total of 1148 breast cancer patients undergoing anthracycline chemotherapy. The primary outcome was the evaluation of changes in RV GLS and RV FWLS pre- and post-chemotherapy. Secondary outcomes included changes in traditional echocardiographic parameters: TAPSE, FAC, and TDI S'. Meta-analysis revealed significant declines in RV function post-chemotherapy across all parameters. RV GLS decreased from 23.99% to 20.35% (SMD: −0.259, p < 0.0001), and RV FWLS from 24.92% to 21.56% (SMD: −0.269, p < 0.0001). Traditional parameters like TAPSE, FAC, and TDI S' also showed reductions, but these were less consistent across studies. A meta-regression analysis showed no significant relationship between post-chemotherapy left ventricular ejection fraction (LVEF) and the changes in RV GLS and RV FWLS, suggesting that RV dysfunction may not be solely a consequence of LV impairment. Conclusions: Anthracycline chemotherapy induces subclinical RV dysfunction in breast cancer patients. RV strain analysis, especially 3D strain, shows greater sensitivity in detecting early dysfunction. However, further research is needed to clarify the clinical significance and prognostic value of these findings, as well as the role of routine RV strain analysis in guiding early interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Doxorubicin is a widely used chemotherapeutic agent for breast cancer but is accompanied by significant side effects due to its systemic delivery. The expression of the transient receptor potential canonical 1 (TRPC1) cation channel subunit correlates with breast cancer progression. This study showed that brief magnetic exposure (10 min) increased doxorubicin uptake into breast cancer cells without harming healthy cells. Heightened TRPC1 expression was correlated with more advanced breast cancer grades as well as with greater doxorubicin uptake. Pharmacologically or genetically silencing TRPC1 activity reduced magnetically induced doxorubicin uptake, whereas overexpression of TRPC1 amplified doxorubicin uptake and increased cancer cell death. This study described a localized and non-invasive magnetic therapy paradigm that could potentially improve breast cancer chemotherapeutic efficacy with less systemically delivered doxorubicin. The loading of TRPC1-enriched cell-derived vesicles with doxorubicin upon magnetic exposure underscored the contribution of TRPC1 in the stimulated uptake of doxorubicin in a minimalized model system. Background/Objectives: Doxorubicin (DOX) is commonly used as a chemotherapeutic agent for the treatment of breast cancer. Nonetheless, its systemic delivery via intravenous injection and toxicity towards healthy tissues commonly result in a broad range of detrimental side effects. Breast cancer severity was previously shown to be correlated with TRPC1 channel expression that conferred upon it enhanced vulnerability to pulsed electromagnetic field (PEMF) therapy. PEMF therapy was also previously shown to enhance breast cancer cell vulnerability to DOX in vitro and in vivo that correlated with TRPC1 expression and mitochondrial respiratory rates. Methods: DOX uptake was assessed by measuring its innate autofluorescence within murine 4T1 or human MCF7 breast cancer cells following magnetic exposure. Cellular vulnerability to doxorubicin uptake was assessed by monitoring mitochondrial activity and cellular DNA content. Results: Here, we demonstrate that 10 min of PEMF exposure could augment DOX uptake into 4T1 and MCF7 breast cancer cells. DOX uptake could be increased by TRPC1 overexpression, whereas inhibiting the activity of TRPC1 channels with SKF-96356 or genetic knockdown, precluded DOX uptake. PEMF exposure enhances DOX-mediated killing of breast cancer cells, reducing the IC50 value of DOX by half, whereas muscle cells, representative of collateral tissues, were less sensitive to PEMF-enhanced DOX-mediated cytotoxicity. Vesicular loading of DOX correlated with TRPC1 expression. Conclusions: This study presents a novel TRPC1-mediated mechanism through which PEMF therapy may enhance DOX cytotoxicity in breast cancer cells, paving the way for the development of localized non-invasive PEMF platforms to improve cancer outcomes with lower systemic levels of DOX. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype, has poor prognosis, and lacks targeted therapies. Schlafen12 (SLFN12) is a protein linked to survival in TNBC. SLFN12 influences the expressions of important cancer genes and other SLFN family members, but it is unclear how these genes change following chemotherapy. This study indicates that SLFN12 overexpressing TNBC cells with chemotherapy agents resulted in the differential expressions of eight cancer genes. Further, when TNBC cells were treated with chemotherapy and hairpin adenovirus to knock down SLFN12, IFN-α2 treatment was able to increase SLFN family mRNA expression and decrease cell viability. Together, these results indicate the importance of examining SLFN family interactions with gene profiles in an effort to produce a targeted treatment approach for TNBC patients. Background/Objectives: Schlafen12 (SLFN12) is an intermediate human Schlafen protein shown to correlate with survivability in triple-negative breast cancer (TNBC). SLFN12 causes differential expressions of significant cancer genes, but how they change in response to chemotherapy remains unknown. Our aim is to identify the effect of chemotherapy on genes that improve TNBC outcomes and other SLFN family members following SLFN12 knockout or overexpression. Methods: We overexpressed SLFN12 using a lentiviral vector and knocked out SLFN12 (AdvShSLFN12) using a hairpin adenovirus in MDA-MB-231 TNBC cells. Cells were treated with camptothecin, paclitaxel, zoledronic acid, or carboplatin to evaluate the SLFN12 signature cancer genes associated with improved TNBC outcomes using qPCR. Additionally, cells were treated alone and in combination with AdvShSLFN12, IFN-α2 (known SLFN12 stimulator), carboplatin, and paclitaxel. After treatment, the viable cell numbers were analyzed utilizing a colorimetric crystal violet assay for cell viability. Results: The SLFN family and SLFN12 cancer signature gene mRNA expressions were analyzed by RT-qPCR. Treating SLFN12-overexpressing TNBC cells with chemotherapy agents resulted in the differential expressions of eight cancer-related genes. Notably, GJB3 was downregulated following treatment with each chemotherapeutic drug. Inducing SLFN12 with IFN-α2 resulted in decreased cell viability and increased SLFN12 mRNA levels following treatment with paclitaxel or carboplatin. Conclusions: These results suggest that SLFN12 overexpression significantly affects the expressions of genes driving phenotypic changes in response to chemotherapy and influences additional SLFN family members following IFN-α2 treatment. This may contribute to improving the survival of patients with SLFN12 overexpression. Additionally, patient SLFN12 levels can be used as a factor when pursuing personalized chemotherapy treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Interactions between breast cancer (BCa) cells and carcinoma-associated fibroblasts (CAFs) in the tumor microenvironment (TME) are critical for cancer development and progression and can mitigate responses to therapies. Historically, it has been difficult to replicate in vivo long-term interactions between BCa cells and CAFs for in vitro studies and to define the precise roles of CAFs in BCa cell progression. Our novel microfluidic-capable culture devices called TAME (tissue architecture and microenvironment engineering) devices enable us to study cell-cell interactions of human breast cancer (BCa) cells and human CAFs through their secretome in 3D cultures for extended periods, up to and beyond 70 days. Using these systems, we observed that CAFs enhance BCa cell progression to an invasive phenotype. Moreover, secretome-mediated reciprocal interactions of BCa cells and CAFs promote their migration toward each other, suggesting that targeting signaling pathways to mediate interactions between BCa cells and CAFs could be a potential therapeutic approach for the prevention of BCa progression. Background/Objectives: Carcinoma-associated fibroblasts (CAFs), a prominent cell type in the tumor microenvironment (TME), significantly contributes to cancer progression through interactions with cancer cells and other TME components. Consequently, targeting signaling pathways driven by CAFs has potential to yield new therapeutic approaches to inhibit cancer progression. However, the mechanisms underlying their long-term interactions with cancer cells in vivo remains poorly understood. Methods: To address this, we developed a three-dimensional (3D) parallel coculture model of human triple-negative breast cancer (TNBC) cells and CAFs using our innovative TAME devices. This model allowed for the analysis of TNBC paracrine interactions via their secretome over extended culture periods (at least 70 days). Results: Using TNBC cell lines (MDA-MB-231, MCF10.DCIS, and HCC70), we found that TNBC spheroids in 3D parallel cocultures with CAFs exhibited more pronounced invasive finger-like outgrowths than those in cocultures of TNBC cells and normal fibroblasts (NFs) over a period of 50–70 days. We also established that the CAF-derived secretome affects TNBC migration towards the CAF secretome region. Additionally, we observed a preferential migration of CAFs, but not NFs, toward TNBC spheroids. Conclusions: Overall, our results suggest that paracrine interactions between TNBC cells and CAFs enhance TNBC invasive phenotypes and promote reciprocal migration. [ABSTRACT FROM AUTHOR]