CTLA4 expression profiles and their association with clinical outcomes of breast cancer: a systemic review.

Purpose: The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. Methods: We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. Results: CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. Conclusion: This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.

Designing a virtual breast cancer prevention program for Iranian women: A study protocol.

BACKGROUND: The growing number of breast cancer patients in Iran, following the lower referrals of women to screening centers after the outbreak of the COVID-19, suggests the need for designing virtual educational interventions to teach self-care methods to women. The aim of this study is to design a virtual training program for the prevention of breast cancer in women based on the steps of the ADDIE (Analysis, Design, Development, Implementation, and Evaluation) educational design model. MATERIALS AND METHODS: This developmental study will be conducted based on the steps of the ADDIE model. In the first step (analysis), a qualitative study, literature review, and a panel of experts will be conducted to analyze the situation (learners, content, platforms, and media for the electronic presentation of the program). In the design step, the learning objectives, educational strategies, and the way of program's implementation and evaluation will be specified. In the third step, not only are the content, storyboard, and educational program developed, but the pilot study is also conducted and formative assessment is performed. In the fourth step, the program will be provided to the audience and will be implemented as a preliminary program. In the final step, the final virtual education program for the prevention of breast cancer in women will be presented based on the results of the evaluation. CONCLUSIONS: Using a comprehensive and systematic educational design model can be a step toward making changes and encouraging innovations in breast cancer prevention education programs in women based on virtual education. Given the existing needs and conditions, this program can promote cancer preventive behaviors as much as possible, reduce the costs imposed on the family and healthcare systems, and lower the complications and mortality rate caused by the delayed diagnosis of the disease.

Transforming breast cancer care: harnessing the power of artificial intelligence and imaging for predicting pathological complete response. a narrative review.

This narrative review explores the transformative potential of Artificial Intelligence (AI) and advanced imaging techniques in predicting Pathological Complete Response (pCR) in Breast Cancer (BC) patients undergoing Neo-Adjuvant Chemotherapy (NACT). Summarizing recent research findings underscores the significant strides made in the accurate assessment of pCR using AI, including deep learning and radiomics. Such AI-driven models offer promise in optimizing clinical decisions, personalizing treatment strategies, and potentially reducing the burden of unnecessary treatments, thereby improving patient outcomes. Furthermore, the review acknowledges the potential of AI to address healthcare disparities in Low- and Middle-Income Countries (LMICs), where accessible and scalable AI solutions may enhance BC management. Collaboration and international efforts are essential to fully unlock the potential of AI in BC care, offering hope for a more equitable and effective approach to treatment worldwide.

Virtual reality-based interventions, a neoteric approach for management and rehabilitation in patients with breast cancer.

Breast cancer (BC) patients and survivors can experience immense emotional and psychosocial trauma. Treatment modalities for BC, including surgery, chemotherapy and radiotherapy are associated with certain displeasing and undesirable effects, including physical restrictions as well as mental stress. However, it has been ascertained that appropriate supportive and rehabilitative strategies can significantly help to alleviate the distress. Along with several conventional physical therapy options, the novel Virtual Reality (VR) tool has opened a new gateway in rehabilitative approaches in patients with BC. We reviewed the role of VR based management for BC-related incapacitations and found that its efficacy is comparable to that of contemporary therapy options. It has the additional benefits of modulating pain perceptions, improving mobility, and overall enhancing the quality of life of BC survivors.

Advancements in oligometastatic breast cancer: a comprehensive review of current strategies and the role of artificial intelligence.

In the dynamic landscape of Breast Cancer (BC), Oligo- Metastatic Breast Cancer (OMBC) presents unique challenges and opportunities. This comprehensive review delves into current strategies for addressing OMBC, covering locoregional and site-specific metastasis management, and addressing both surgical and minimally invasive therapies as essential components. Moreover, the transformative role of Artificial Intelligence (AI) is spotlighted. However, while the future looks promising, several limitations need addressing, including the need for further research, especially in diverse patient populations and resource-challenged settings. AI implementation may require overcoming the lack of Electronic Health Records acceptance in resource-challenged countries, which contributes to a scarcity of large datasets for AI training. As AI continues to evolve, validation and regulatory aspects must be continually addressed for seamless integration into clinical practice. In summary, this review outlines the evolving landscape of OMBC management, emphasizing the need for comprehensive research, global collaboration, and innovative AI solutions to enhance patient care and outcomes.

Female Sexual Function Index Adaptation for Breast Cancer Patients (FSFI-BC): Brazilian Portuguese Translation and Cultural Adaptation.

BACKGROUND: The assessment of female sexual function after diagnosis and treatment of breast cancer is relevant, as cancer can negatively affect sexuality and, therefore, quality of life. Instruments assessing female sexuality can be useful in clinical practice. However, there are few validated instruments available for this purpose. This study aimed to translate the Female Sexual Function Index Adaptation for Breast Cancer Patients (FSFI-BC) into Brazilian Portuguese and culturally adapt it for use in Brazil. PATIENTS AND METHODS: Translation and cross-cultural adaptation followed the linguistic validation process, according to international guidelines. The instrument was translated and back-translated by independent translators. Sixty women aged 25 to 70 years who had been diagnosed and surgically treated for breast cancer at least 6 months previously participated in the cultural adaptation process. Participants were stratified into sexually active or inactive. Internal consistency was analyzed using Cronbach's alpha coefficient. RESULTS: Mean participant age was 52.5 years. For sexually active women, reliability analysis (Cronbach's alpha) showed excellent internal consistency between the items of the subscales 'Desire/Arousal' (α = 0.912) and 'Orgasm' (α = 0.904), and good internal consistency for 'Lubrication' (α = 0.814) and 'Pain' (α = 0.839). For sexually inactive women, excellent internal consistency was observed between the items of the subscale 'Reason for Inactivity - difficulty lubricating' (α = 0.930), and good internal consistency for the other subscales. The instrument had face and content validity. CONCLUSIONS: FSFI-BC was translated and culturally adapted to the context of the Brazilian population.

Demand analysis of health care services for community-dwelling breast cancer survivors based on the Kano model: A cross-sectional study.

Objectives: Providing satisfactory healthcare services for breast cancer survivors can effectively reduce their burden and the pressure on medical resources. The aim of this study was to explore health care service demands for community-dwelling breast cancer survivors using the Kano model. Methods: A cross-sectional survey was conducted from January to March 2023 among breast cancer survivors discharged from a tertiary cancer hospital. Participants were asked to fill out a self-designed questionnaire involving the Kano model, which helped to categorize and prioritize the attributes of healthcare services. The questionnaire included 30 health care services. Additionally, their social demographic characteristics were collected during the survey. Results: A total of 296 valid questionnaires were collected, and demand attributes of the 30 health care services were evaluated. The findings revealed that one of 30 services was classified as "must-be attributes" (body image management), 13 as "one-dimensional attributes" (focused on medical security support, health management, and health counseling), 3 as "attractive attributes" (focused on communication needs and telehealth services), and 11 as "indifferent attributes" (mainly in the area of psycho-social services). Conclusions: Breast cancer survivors in the community have different levels of need for various health care services. It's crucial for healthcare providers to identify these needs and devise effective strategies to deliver the appropriate services. Services with must-be and one-dimensional attributes should be given priority, and efforts should be made to provide services with attractive attributes, hence improving the quality of life of breast cancer survivors.

Wait times and breast cancer survival: a population-based retrospective cohort study using CanIMPACT data.

PURPOSE: The time from breast cancer surgery to chemotherapy has been shown to affect survival outcomes; however, the effect of time from first breast cancer-related healthcare contact to first cancer specialist consultation, or the time from first breast cancer-related healthcare contact to adjuvant chemotherapy on survival has not been well explored. We aimed to determine whether various wait times along the breast cancer treatment pathway (contact-to-consultation, contact-to-chemotherapy, surgery-to-chemotherapy) were associated with overall survival in women within the Canadian province of Ontario. METHODS: We performed a population-based retrospective cohort study of women diagnosed with stage I-III breast cancer in Ontario between 2007 and 2011 who received surgery and adjuvant chemotherapy. This was the Ontario cohort of a larger, nationwide study (the Canadian Team to improve Community-Based Cancer Care along the Continuum - CanIMPACT). We used Cox-proportional hazards regression to determine the association between the contact-to-consultation, contact-to-chemotherapy, and surgery-to-chemotherapy intervals and overall survival while adjusting for cancer stage, age, comorbidity, neighborhood income, immigration status, surgery type, and method of cancer detection. RESULTS: Among 12,782 breast cancer patients, longer surgery-to-chemotherapy intervals (HR 1.13, 95% CI 1.03-1.18 per 30-day increase), but not the contact-to-consultation (HR 0.979, 95% CI 0.95-1.01 per 30-day increase), nor the more comprehensive contact-to-chemotherapy intervals (HR 1.00, 95% CI 0.98-1.02 per 30-day increase) were associated with decreased survival in our adjusted analyses. CONCLUSION: Our findings emphasize the prognostic importance of a shorter surgery-to-chemotherapy interval, whereas the contact-to-consultation and contact-to-chemotherapy intervals have less impact on survival outcomes.

Axillary lymph node metastasis in pure mucinous carcinoma of breast: clinicopathologic and ultrasonographic features.

BACKGROUND: The purpose of this research is to study the sonographic and clinicopathologic characteristics that associate with axillary lymph node metastasis (ALNM) for pure mucinous carcinoma of breast (PMBC). METHODS: A total of 176 patients diagnosed as PMBC after surgery were included. According to the status of axillary lymph nodes, all patients were classified into ALNM group (n = 15) and non-ALNM group (n = 161). The clinical factors (patient age, tumor size, location), molecular biomarkers (ER, PR, HER2 and Ki-67) and sonographic features (shape, orientation, margin, echo pattern, posterior acoustic pattern and vascularity) between two groups were analyzed to unclose the clinicopathologic and ultrasonographic characteristics in PMBC with ALNM. RESULTS: The incidence of axillary lymph node metastasis was 8.5% in this study. Tumors located in the outer side of the breast (upper outer quadrant and lower outer quadrant) were more likely to have lymphatic metastasis, and the difference between the two group was significantly (86.7% vs. 60.3%, P = 0.043). ALNM not associated with age (P = 0.437). Although tumor size not associated with ALNM(P = 0.418), the tumor size in ALNM group (32.3 ± 32.7 mm) was bigger than non-ALNM group (25.2 ± 12.8 mm). All the tumors expressed progesterone receptor (PR) positively, and 90% of all expressed estrogen receptor (ER) positively, human epidermal growth factor receptor 2 (HER2) were positive in two cases of non-ALNM group. Ki-67 high expression was observed in 36 tumors in our study (20.5%), and it was higher in ALNM group than non-ALNM group (33.3% vs. 19.3%), but the difference wasn't significantly (P = 0.338). CONCLUSIONS: Tumor location is a significant factor for ALNM in PMBC. Outer side location is more easily for ALNM. With the bigger size and/or Ki-67 higher expression status, the lymphatic metastasis seems more likely to present.

Real-world effectiveness of CDK4/6 inhibitors on patients with HR+/HER2- advanced breast cancer in South Korea, focusing on underrepresented patients.

OBJECTIVE: We assessed the real-world effectiveness of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors as first-line treatments in postmenopausal patients with HR+/HER2- advanced breast cancer, focusing on younger (<45 years) and older (>78 years) populations not considered in clinical trials. METHODS: We analyzed nationwide claims data from the Health Insurance Review and Assessment Service between November 2016 and February 2021. In this retrospective cohort study, patients using CDK4/6 inhibitors and aromatase inhibitors were selected and grouped by age as follows: 45-78 years (trial-enrolled), <45 years (younger), and >78 years (older). We estimated the median real-world progression-free survival (rwPFS) and overall survival (OS) using the Kaplan-Meier method. We conducted Cox regression analysis using a sub-distribution hazard model to evaluate risk factors (age, history of prior systemic treatment, presence of metastasis, comorbidity index, and type of provider) and estimated hazard ratios (HR). RESULTS: Among the 2,830 patients who received CDK4/6 inhibitors as first-line therapy, we identified 358 (12.65%) younger and 148 (5.23%) older underrepresented patients. The younger patient group (50.84%) had the highest rate of prior systemic therapy, followed by the trial-enrolled (25.39%) and older patient groups (8.11%). The median rwPFS was shorter in the older group (19.30 months) than those in the younger and the trial-enrolled age groups (30.33 and 34.53 months, respectively; p = .002). The HR of older age for death was 1.59 (95% confidence interval (CI) = 1.24-2.03). For rwPFS, the HR of prior systemic therapy was 1.19 (95% CI = 1.04-1.37). CONCLUSIONS: The younger age group, which was underrepresented in the trial, did not show a significant difference in risk compared with the enrolled age group. However, the older age group, which was also underrepresented in the trial, faces a risk of mortality but not progression. Patients who fall outside the specified age groups for the clinical trial can still expect the same level of effectiveness in terms of progression.

Biological effects of intraoperative radiation therapy: histopathological changes and immunomodulation in breast cancer patients.

Introduction: Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation. Methods: Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11). Results: Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p=0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death (p<0.001). Using the xCell algorithm, we inferred a higher abundance of γδ T-cells, dendritic cells, and monocytes in the IORT samples. Conclusion: IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/HER2-negative breast cancer.

Optimizing ultrafast dynamic contrast-enhanced MRI scan duration in the differentiation of benign and malignant breast lesions.

OBJECTIVE: To determine the optimal scan duration for ultrafast DCE-MRI in effectively differentiating benign from malignant breast lesions. METHODS: The study prospectively recruited participants who underwent breast ultrafast DCE-MRI from September 2021 to March 2023. A 30-phase breast ultrafast DCE-MRI on a 3.0-T MRI system was conducted with a 4.5-s temporal resolution. Scan durations ranged from 40.5 s to 135.0 s, during which the analysis is performed at three-phase intervals, forming eight dynamic sets (scan duration [SD]40.5s: 40.5 s, SD54s: 54.0 s, SD67.5s: 67.5 s, SD81s: 81.0 s, SD94.5s: 94.5 s, SD108s: 108.0 s, SD121.5s: 121.5 s, and SD135s: 135.0 s). Two ultrafast DCE-MRI parameters, maximum slope (MS) and initial area under the curve in 60 s (iAUC), were calculated for each dynamic set and compared between benign and malignant lesions. Areas under the receiver operating characteristic curve (AUCs) were used to assess their diagnostic performance. RESULTS: A total of 140 women (mean age, 47 ± 11 years) with 151 lesions were included. MS and iAUC from eight dynamic sets exhibited significant differences between benign and malignant lesions (all p < 0.05), except iAUC at SD40.5s. The AUC of MS (AUC = 0.804) and iAUC (AUC = 0.659) at SD67.5s were significantly higher than their values at SD40.5s (AUC = 0.606 and 0.516; corrected p < 0.05). No significant differences in AUCs for MS and iAUC were observed from SD67.5s to SD135s (all corrected p > 0.05). CONCLUSIONS: Ultrafast DCE-MRI with a 67.5-s scan duration appears optimal for effectively differentiating malignant from benign breast lesions. CRITICAL RELEVANCE STATEMENT: By evaluating scan durations (40.5-135 s) and analyzing two ultrafast DCE-MRI parameters, we found a scan duration of 67.5 s optimal for discriminating between these lesions and offering a balance between acquisition time and diagnostic efficacy. KEY POINTS: Ultrafast DCE-MRI can effectively differentiate malignant from benign breast lesions. A minimum of 67.5-sec ultrafast DCE-MRI scan duration is required to differentiate benign and malignant lesions. Extending the scan duration beyond 67.5 s did not significantly improve diagnostic accuracy.

Potential rapid intraoperative cancer diagnosis using dynamic full-field optical coherence tomography and deep learning: A prospective cohort study in breast cancer patients.

An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin (H&E) histology, such as frozen section, are time-, resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography (D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group (n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma (IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ (DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests (n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%; only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow (approximately 3 min) was significantly shorter than that required for traditional procedures (approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.

Pilot randomized controlled trial of a program to enhance experience and adherence with adjuvant endocrine therapy among women with non-metastatic breast cancer: 12-month quantitative results.

PURPOSE: Adjuvant endocrine therapy (AET) reduces recurrence risk after hormone receptor-positive breast cancer, but non-adherence is common. We pilot-tested SOIE, a program to enhance AET experience and adherence, to assess its acceptability, feasibility, and effects on psychosocial precursors of AET adherence. METHODS: We conducted a 12-month pilot randomized controlled trial among women who had a first AET prescription. Intervention group received SOIE while control group received usual care. Psychosocial factors from the Theory of Planned Behavior (TPB) (intention - primary outcome -, attitude, subjective norm, behavioral control), additional constructs (AET knowledge, social support, coping planning), impact of AET services received, and adherence were measured by questionnaires at baseline, 3-month, and 12-month endpoints. Group patterns were compared using repeated measures analyses with generalized estimating equations. RESULTS: A total of 106 women were randomized (participation = 54.9%; intervention n = 52; control n = 54; retention = 93.8%). Among SOIE women, ≥ 90% received the program components and were satisfied. Both groups scored high on adherence intentions and group patterns over time were not statistically different. In the intervention group, AET knowledge and coping planning with side effects increased (group-by-time p-value = .002 and .016), a higher proportion reported that AET services received helped them take their AET (p < .05) and have a consistent daily intake (p = .01). CONCLUSION: SOIE is feasible and acceptable for survivors with an AET. SOIE did not significantly impact adherence intentions but was beneficial for other program outcomes and daily intake. IMPLICATIONS FOR CANCER SURVIVORS: SOIE may represent an encouraging avenue to enhance supportive care and empower survivors with managing AET.

Prevalence and clinical implications of sarcopenia in breast cancer: a systematic review and meta-analysis.

PURPOSE: The impact of sarcopenia in oncology is increasingly recognized, yet little is known about its clinical implications in breast cancer. This systematic review and meta-analysis estimates the overall prevalence of sarcopenia in breast cancer, quantifies skeletal muscle index (SMI), and comprehensively evaluates sarcopenia's impact on clinical outcomes. METHODS: We systematically searched primary original research published before June 2023 in four databases: the Cochrane Library via Wiley, CINAHL Plus with Full Text, Embase via Elsevier Excerpta Medica, and Medline via Ovid. Standardized mean SMI and 95% confidence interval (CI) were calculated by applying the random-effects model. The methodological quality of the included studies was assessed using the National Institutes of Health quality assessment checklist. RESULTS: The systematic review included 17 studies with a total of 9863 patients; the meta-analysis included 12 of these studies. The mean prevalence of sarcopenia in breast cancer (stages I-III) was 32.5%. The mean SMI assessed by CT was 43.94 cm2/m2 (95% CI 42.87, 45.01; p < .01). Overall, low muscle mass was associated with chemotherapy toxicities, dose reductions, dose delays, or treatment discontinuation. Low muscle mass was generally associated with poor survival, but in some studies, this association was not significant or reversed direction. CONCLUSION: Sarcopenia is not just a state of muscle mass loss, but an influencing factor on therapeutic effects and survival rates in oncology. It is thus necessary to recognize the risk of sarcopenia throughout the trajectory of cancer treatment, identify low muscle mass early, and manage it from a prehabilitation perspective.

Associations of pre-diagnosis physical activity with treatment tolerance and treatment efficacy in breast cancer patients with neoadjuvant chemotherapy.

PURPOSE: Higher pre-diagnosis physical activity (PA) is associated with lower all-cause mortality in breast cancer (BCa) patients. However, the association with pathological complete response (pCR) is unclear. We investigated the association between pre-diagnosis PA level and chemotherapy completion, dose delay, and pCR in BCa patients receiving neoadjuvant chemotherapy (NACT). METHODS: 180 stage I-III BCa patients receiving NACT (mean [SD] age of diagnosis: 60.8 [8.8] years) in the Sister Study were included. Self-reported recreational and total PA levels were converted to metabolic equivalent of task-hours per week (MET-hrs/wk). The pCR was defined as no invasive or in situ residual in breast or lymph node (ypT0 ypN0). Multivariable logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) for treatment outcomes. RESULTS: In this sample, 45 (25.0%) BCa patients achieved pCR. Higher pre-diagnosis recreational PA was not associated with lower likelihood of chemotherapy completion (highest vs. lowest tertile: OR = 0.87, 95% CI = 0.30-2.56; Ptrend = 0.84), greater dose delay (OR = 1.45, 95% CI = 0.54-3.92; Ptrend = 0.46), or greater odds of pCR (OR = 1.28, 95% CI = 0.49-3.34; Ptrend = 0.44). Associations were similar for pre-diagnosis total PA. Meeting the recommended level of recreational PA was not associated with pCR overall (≥ 7.5 vs. < 7.5 MET-hrs/wk: OR = 1.33, 95% CI = 0.59-3.01). CONCLUSIONS: Although small sample size and limited information on exercise closer to time of diagnosis limit interpretation, pre-diagnosis PA was not convincingly associated with treatment tolerance or treatment efficacy in BCa patients receiving NACT. Future investigations are needed to better understand the impact of pre-diagnosis PA on BCa treatment.

Risk factors for recurrence in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer in Japan: a systematic literature review and meta-analysis.

BACKGROUND: The clinicopathological factors indicating risk of recurrence are used to guide the choice of perioperative therapy in patients with breast cancer. Although several risk factors for recurrence have been reported in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer in Japan, there has been no systematic review quantifying potential risk factors. METHODS: We performed a systematic literature review and meta-analysis using the MEDLINE, Embase, Cochrane CENTRAL, and Japan Medical Abstract Society databases to identify risk factors for recurrence in HR+/HER2- early breast cancer in Japan. The primary outcome was relapse-free or disease-free survival (RFS/DFS), and the secondary outcomes were overall survival and breast cancer-specific survival (BCSS). RESULTS: Searches identified 42 eligible publications. Meta-analyses identified lymph node metastasis (hazard ratio: 2.76 [95% confidence interval: 1.97-3.88]), large tumor size (1.67 [1.24-2.23]), high histological grade (1.50 [1.04-2.16]), and high nuclear grade (2.02 [1.61-2.54]) as risk factors for RFS/DFS. Lymph node metastasis (2.43 [1.28-4.63]), large tumor size (1.80 [1.24-2.62]), and high histological grade (2.02 [1.44-2.84]) were also risk factors for overall survival, and high progesterone status was a possible favorable prognostic factor for BCSS (0.20 [0.10-0.42]). CONCLUSIONS: Identified risk factors were consistent with the previous reports, and this study provides quantitative summary of risk factors for HR+/HER2- early breast cancer recurrence in Japan. (PROSPERO Registration ID, CRD42022338391.).

Impact of Dose Calculation Algorithms and Radiobiological Parameters on Prediction of Cardiopulmonary Complications in Left Breast Radiation Therapy.

Background: Breast cancer requires evaluating treatment plans using dosimetric and biological parameters. Considering radiation dose distribution and tissue response, healthcare professionals can optimize treatment plans for better outcomes. Objective: This study aimed to evaluate the effects of the different Dose Calculation Algorithms (DCAs) and Biologically Model-Related Parameters (BMRPs) on the prediction of cardiopulmonary complications due to left breast radiotherapy. Material and Methods: In this practical study, the treatment plans of 21 female patients were simulated in the Monaco Treatment Planning System (TPS) with a prescribed dose of 50 Gy in 25 fractions. Dose distribution was extracted using the three DCAs [Pencil Beam (PB), Collapsed Cone (CC), and Monte Carlo (MC)]. Cardiopulmonary complications were predicted by Normal Tissue Complication Probability (NTCP) calculations using different dosimetric and biological parameters. The Lyman-Kutcher-Burman (LKB) and Relative-Seriality (RS) models were used to calculate NTCP. The endpoint for NTCP calculation was pneumonitis, pericarditis, and late cardiac mortality. The ANOVA test was used for statistical analysis. Results: In calculating Tumor Control Probability (TCP), a statistically significant difference was observed between the results of DCAs in the Poisson model. The PB algorithm estimated NTCP as less than others for all Pneumonia BMRPs. Conclusion: The impact of DCAs and BMRPs differs in the estimation of TCP and NTCP. DCAs have a stronger influence on TCP calculation, providing more effective results. On the other hand, BMRPs are more effective in estimating NTCP. Consequently, parameters for radiobiological indices should be cautiously used s to ensure the appropriate consideration of both DCAs and BMRPs.

French national survey on breast cancer care: caregiver and patient views.

PURPOSE: To improve the quality of care for patients with breast cancer, an analysis of the health-care pathway, considering feedback from both health-care practitioners (HCPs) and patients, is needed. METHODS: Between 2020 and 2022, we conducted a survey at French breast cancer centers and analyzed information from questionnaires completed by HCPs and patients. We collected information on center organization, diagnostic processes, treatment decisions and modalities, supportive care, patient advocacy groups, and work issues. RESULTS: Twenty-three breast cancer centers were included and questionnaires completed by 247 HCPs and 249 patients were analyzed. The centers closely followed the legal French framework for cancer treatments, which includes formal diagnostic announcements, multidisciplinary tumor boards, personalized treatment summaries, and supportive care access. HCPs and patients were satisfied with the time to diagnosis (≤ 2 weeks as evaluated by 75% of patients), time to surgery (mean 61 days), time between surgery and chemotherapy (mean 47 days), and time between surgery and radiotherapy (mean 81 days). Fertility preservation counseling for women under 40 years of age was systematically offered by 67% of the HCPs. The majority (67%) of the patients indicated that they had received a personalized treatment summary; the topics discussed included treatments (92%), tumor characteristics (84%), care pathways (79%), supportive care (52%), and breast reconstruction (33%). Among HCPs, 44% stated that reconstructive surgery was offered to all eligible patients and 57% and 45% indicated coordination between centers and primary care physicians for adverse effects management and access to supportive care should be improved, for chemotherapy and radiotherapy, respectively. Regarding patient advocacy groups, 34% of HCPs did not know whether patients had contact and only 23% of patients declared that they had such contact. For one-third of working patients, work issues were not discussed. Twenty-eight percent of patients claimed that they had faced difficulties for supportive care access. Among HCPs, 13% stated that a formal personalized survivorship treatment program was administered to almost all patients and 37% almost never introduced the program to their patients. Compliance to oral treatments was considered very good for 75-100% of patients by 62% of HCPs. CONCLUSIONS: This study provides an updated analysis of breast cancer care pathways in France. Overall, the initial processes of diagnosis, announcement, and treatment were swift and were in agreement with the best care standards. No barriers to accessing care were identified. Based on the study findings, we proposed several strategies to improve the quality of care for patients in supportive care, coordination with primary care physicians, reconstructive surgery, and fertility preservation access.

Annexin-A5 Overexpression Increases Sensitivity of MCF-7 and MCF-7/ADR Cells to Epirubicin.

Background: Multi-drug resistance is an important challenge in the chemotherapy of cancer. The role of annexin A5 (ANXA5) in the biology of cancer has been the focus of many studies. Breast Cancer (BC) is frequent cancer in women with high morbidity and mortality rate. The present study aimed to investigate the effects of ANXA5 overexpression on the anti-tumor activity of Epirubicin (EPI) in MCF-7 and MCF-7/ADR cells. Methods: MCF-7 and MCF-7/ADR cells were transfected with the pAdenoVator-CMV-ANXA5-IRES-GFP plasmid or mock plasmid. The overexpression of ANXA5 was evaluated using qPCR. The effects of ANXA5 overexpression and EPI on the cell viability of MCF-7 and MCF-7/ADR cells were measured using an MTT assay. Cell apoptosis was measured by annexin V/7-AAD flow cytometry assay. Results: Following the overexpression of ANXA5, the viability of MCF-7 and MCF-7/ADR was significantly decreased. Furthermore, the overexpression of ANXA5 in MCF-7 cells increased the cytotoxic effects of EPI in all doses and reduced the IC50 of EPI from 17.69 µM to 4.07 µM. Similarly, the overexpression of ANXA5 in MCF7-ADR cells reduced the IC50 of EPI from 27.3 µM to 6.69 µM. ANXA5 overexpression alone or combined with EPI treatment increased the apoptosis of MCF7 and MCF7-ADR cells. Conclusion: The results of the present study demonstrate that ANXA5 overexpression increases the sensitivity of MCF-7 and MCF-7/ADR to EPI, suggesting a possible beneficial role of ANXA5 in the therapy of BC.