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19 pages, 1632 KiB  
Guidelines
Multidisciplinary Practical Guidance for Implementing Adjuvant CDK4/6 Inhibitors for Patients with HR-Positive, HER2-Negative Early Breast Cancer in Canada
by Katarzyna J. Jerzak, Sandeep Sehdev, Jean-François Boileau, Christine Brezden-Masley, Nadia Califaretti, Scott Edwards, Jenn Gordon, Jan-Willem Henning, Nathalie LeVasseur and Cindy Railton
Curr. Oncol. 2025, 32(8), 444; https://doi.org/10.3390/curroncol32080444 - 7 Aug 2025
Abstract
Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard [...] Read more.
Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard endocrine therapy has demonstrated clinically meaningful improvements in invasive disease-free survival, supported by the monarchE and NATALEE trials, respectively. With expansion of patient eligibility for CDK4/6 inhibitors, multidisciplinary coordination among medical oncologists, surgeons, nurses, pharmacists, and other health care providers is critical to optimizing patient identification, monitoring, and management of adverse events. This expert guidance document provides practical recommendations for implementing adjuvant CDK4/6 inhibitor therapy in routine clinical practice, incorporating insights from multiple specialties and with patient advocacy representation. Key considerations include patient selection based on clinical trial data, treatment duration, dosing schedules, adverse event profiles, monitoring requirements, drug–drug interactions, and patient-specific factors such as tolerability, cost, and quality of life. This guidance aims to support Canadian clinicians in effectively integrating CDK4/6 inhibitors into clinical practice, ensuring optimal patient outcomes through a multidisciplinary and patient-centric approach. Full article
(This article belongs to the Section Breast Cancer)
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19 pages, 371 KiB  
Review
Human Breast Milk as a Biological Matrix for Assessing Maternal and Environmental Exposure to Dioxins and Dioxin-like Polychlorinated Biphenyls: A Narrative Review of Determinants
by Artemisia Kokkinari, Evangelia Antoniou, Kleanthi Gourounti, Maria Dagla, Aikaterini Lykeridou, Stefanos Zervoudis, Eirini Tomara and Georgios Iatrakis
Pollutants 2025, 5(3), 25; https://doi.org/10.3390/pollutants5030025 - 7 Aug 2025
Abstract
(1) Background: Dioxins and dioxin-like polychlorinated biphenyls (dl-PCBs) are persistent organic pollutants (POPs), characterized by high toxicity and strong lipophilicity, which promote their bioaccumulation in human tissues. Their detection in breast milk raises concerns about early-life exposure during lactation. Although dietary intake is [...] Read more.
(1) Background: Dioxins and dioxin-like polychlorinated biphenyls (dl-PCBs) are persistent organic pollutants (POPs), characterized by high toxicity and strong lipophilicity, which promote their bioaccumulation in human tissues. Their detection in breast milk raises concerns about early-life exposure during lactation. Although dietary intake is the primary route of maternal exposure, environmental pathways—including inhalation, dermal absorption, and residential proximity to contaminated sites—may also significantly contribute to the maternal body burden. (2) Methods: This narrative review examined peer-reviewed studies investigating maternal and environmental determinants of dioxin and dl-PCB concentrations in human breast milk. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science (2000–2024), identifying a total of 325 records. Following eligibility screening and full-text assessment, 20 studies met the inclusion criteria. (3) Results: The included studies consistently identified key exposure determinants, such as high consumption of animal-based foods (e.g., meat, fish, dairy), living near industrial facilities or waste sites, and maternal characteristics including age, parity, and body mass index (BMI). Substantial geographic variability was observed, with higher concentrations reported in regions affected by industrial activity, military pollution, or inadequate waste management. One longitudinal study from Japan demonstrated a declining trend in dioxin levels in breast milk, suggesting the potential effectiveness of regulatory interventions. (4) Conclusions: These findings highlight that maternal exposure to dioxins is influenced by identifiable environmental and behavioral factors, which can be mitigated through public health policies, targeted dietary guidance, and environmental remediation. Breast milk remains a critical bioindicator of human exposure. Harmonized, long-term research is needed to clarify health implications and minimize contaminant transfer to infants, particularly among vulnerable populations. Full article
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12 pages, 2334 KiB  
Article
Quantitative Analysis of Small Particles Present in Surgical Smoke Generated During Breast Surgery
by Masatake Hara, Goshi Oda, Kumiko Hayashi, Mio Adachi, Yuichi Kumaki, Toshiyuki Ishiba, Emi Yamaga, Tomoyuki Fujioka, Tsuyoshi Nakagawa, Hiroki Mori and Tomoyuki Aruga
Medicina 2025, 61(8), 1422; https://doi.org/10.3390/medicina61081422 - 7 Aug 2025
Abstract
Background and Objectives: Surgical smoke generated by energy devices during surgery contains hazardous substances and poses health risks to staff in the operating room. Exposure to surgical smoke must be reduced to minimize the risk of health hazards. Many studies have evaluated [...] Read more.
Background and Objectives: Surgical smoke generated by energy devices during surgery contains hazardous substances and poses health risks to staff in the operating room. Exposure to surgical smoke must be reduced to minimize the risk of health hazards. Many studies have evaluated surgical smoke qualitatively, but few have performed quantitative assessment. The aim of this study was to quantify the number of particles generated during various breast surgery procedures. Materials and Methods: In this prospective, randomized study, breast surgeries performed at Tokyo Medical and Dental University Hospital (the present Institute of Science Tokyo Hospital) between December 2022 and August 2023 were randomly assigned to two groups: the electrosurgical device group and the electrosurgical device with smoke evacuator group. The number of particles generated by energy devices during surgery was measured using a particle counter. Results: Surgical smoke was generated in all procedures. The number of measured particles was significantly less in the electrosurgical device with smoke evacuator group than in the electrosurgical device group during all procedures (all p < 0.001). Conclusions: All breast surgery procedures produced a significant amount of surgical smoke, which was effectively reduced by using an electrosurgical device with a smoke evacuator. These findings support the routine use of smoke evacuators in breast surgery to reduce occupational exposure to hazardous particles. Implementation of such devices could improve operating room safety and may inform future guidelines and institutional policies regarding surgical smoke management. Full article
(This article belongs to the Section Surgery)
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19 pages, 1628 KiB  
Review
The Role of Non-Coding RNAs in the Regulation of Oncogenic Pathways in Breast and Gynaecological Cancers
by Ammar Ansari, Aleksandra Szczesnowska, Natalia Haddad, Ahmed Elbediwy and Nadine Wehida
Non-Coding RNA 2025, 11(4), 61; https://doi.org/10.3390/ncrna11040061 - 6 Aug 2025
Abstract
Female cancers such as breast and gynaecological cancers contribute to a significant global health burden and are a leading cause of fatality among women. With current treatment options often limited by resistance to cytotoxic drugs, side effects and lack of specificity to the [...] Read more.
Female cancers such as breast and gynaecological cancers contribute to a significant global health burden and are a leading cause of fatality among women. With current treatment options often limited by resistance to cytotoxic drugs, side effects and lack of specificity to the cancer, there is a pressing need for alternative treatments. Recent research has highlighted the promising role of non-coding RNAs (ncRNA) in regulating these issues and providing more targeted approaches to suppressing key cancer pathways. This review explores the involvement of the various types of non-coding RNAs in regulating key oncogenic pathways, namely, the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin and p53 pathways, in a range of female cancers such as breast, cervical, ovarian and endometrial cancers. Evidence from a multitude of studies suggests that non-coding RNAs function as double-edged swords, serving as both oncogenes and tumour suppressors, depending on their expression and cellular interactions. By mapping and investigating these regulatory interactions, this review demonstrates the complexity and dual functionality of ncRNAs in cancer. Understanding these complex mechanisms is essential for the development of new and effective ncRNA-based diagnostic methods and targeted therapies in female cancer treatment. Full article
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16 pages, 2030 KiB  
Article
Myocardial Strain Measurements Obtained with Fast-Strain-Encoded Cardiac Magnetic Resonance for the Risk Prediction and Early Detection of Chemotherapy-Related Cardiotoxicity Compared to Left Ventricular Ejection Fraction
by Daniel Lenihan, James Whayne, Farouk Osman, Rafael Rivero, Moritz Montenbruck, Arne Kristian Schwarz, Sebastian Kelle, Pia Wülfing, Susan Dent, Florian Andre, Norbert Frey, Grigorios Korosoglou and Henning Steen
Diagnostics 2025, 15(15), 1948; https://doi.org/10.3390/diagnostics15151948 - 3 Aug 2025
Viewed by 267
Abstract
Background: Breast and hematological cancer treatments, especially with anthracyclines, have been shown to be associated with an increased risk of cardiotoxicity (CTX). An accurate prediction of cardiotoxicity risk and early detection of myocardial injury may allow for effective cardioprotection to be instituted and [...] Read more.
Background: Breast and hematological cancer treatments, especially with anthracyclines, have been shown to be associated with an increased risk of cardiotoxicity (CTX). An accurate prediction of cardiotoxicity risk and early detection of myocardial injury may allow for effective cardioprotection to be instituted and tailored to reverse cardiac dysfunction and prevent the discontinuation of essential cancer treatments. Objectives: The PRoactive Evaluation of Function to Evade Cardio Toxicity (PREFECT) study sought to evaluate the ability of fast-strain-encoded (F-SENC) cardiac magnetic resonance imaging (CMR) and 2D echocardiography (2D Echo) to stratify patients at risk of CTX prior to initiating cancer treatment, detect early signs of cardiac dysfunction, including subclinical CTX (sub-CTX) and CTX, and monitor for recovery (REC) during cardioprotective therapy. Methods: Fifty-nine patients with breast cancer or lymphoma were prospectively monitored for CTX with F-SENC CMR and 2D Echo over at least 1 year for evidence of cardiac dysfunction during anthracycline based chemotherapy. F-SENC CMR also monitored myocardial deformation in 37 left ventricular (LV) segments to obtain a MyoHealth risk score based on both longitudinal and circumferential strain. Sub-CTX and CTX were classified based on pre-specified cardiotoxicity definitions. Results: CTX was observed in 9/59 (15%) and sub-CTX in 24/59 (41%) patients undergoing chemotherapy. F-SENC CMR parameters at baseline predicted CTX with a lower LVEF (57 ± 5% vs. 61 ± 5% for all, p = 0.05), as well as a lower MyoHealth (70 ± 9 vs. 79 ± 11 for all, p = 0.004) and a worse global circumferential strain (GCS) (−18 ± 1 vs. −20 ± 1 for all, p < 0.001). Pre-chemotherapy MyoHealth had a higher accuracy in predicting the development of CTX compared to CMR LVEF and 2D Echo LVEF (AUC = 0.85, 0.69, and 0.57, respectively). The 2D Echo parameters on baseline imaging did not stratify CTX risk. F-SENC CMR obtained good or excellent images in 320/322 (99.4%) scans. During cancer treatment, MyoHealth had a high accuracy of detecting sub-CTX or CTX (AUC = 0.950), and the highest log likelihood ratio (indicating a higher probability of detecting CTX) followed by F-SENC GLS and F-SENC GCS. CMR LVEF and CMR LV stroke volume index (LVSVI) also significantly worsened in patients developing CTX during cancer treatment. Conclusions: F-SENC CMR provided a reliable and accurate assessment of myocardial function during anthracycline-based chemotherapy, and demonstrated accurate early detection of CTX. In addition, MyoHealth allows for the robust identification of patients at risk for CTX prior to treatment with higher accuracy than LVEF. Full article
(This article belongs to the Special Issue New Perspectives in Cardiac Imaging)
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21 pages, 1031 KiB  
Article
Waiting Times for Surgery and Radiotherapy Among Breast Cancer Patients in Switzerland: A Cancer Registry-Based Cross-Sectional and Longitudinal Analysis
by Christoph Oehler, Michel Eric Nicolas Zimmermann, Mohsen Mousavi, Kattic Ram Joorawon, Marcel Blum, Christian Herrmann and Daniel Rudolf Zwahlen
Radiation 2025, 5(3), 23; https://doi.org/10.3390/radiation5030023 - 3 Aug 2025
Viewed by 264
Abstract
Background: Delays in breast cancer treatment negatively affect prognosis and have increased over time. Data on waiting times in Switzerland are limited. Patients and Methods: This study analyzed cancer registry data from 2003 to 2005 (2628 patients) and 2015 to 2017 (421 patients) [...] Read more.
Background: Delays in breast cancer treatment negatively affect prognosis and have increased over time. Data on waiting times in Switzerland are limited. Patients and Methods: This study analyzed cancer registry data from 2003 to 2005 (2628 patients) and 2015 to 2017 (421 patients) to evaluate waiting times for diagnosis, surgery, and radiotherapy; temporal trends; and survival in women with stage I–III invasive breast cancer treated with surgery without chemotherapy. Associations with demographic/clinical factors and overall survival (OS) were assessed using ANOVA, uni-/multivariable regression, Kaplan–Meier, and Cox regression. Results: From 2003 to 2005, mean intervals were biopsy-to-diagnosis 4.3 days, diagnosis-to-surgery 18.8 days, biopsy-to-surgery 26.8 days, and surgery-to-radiotherapy 56.7 days. Longer diagnosis-to-surgery times were associated with metropolitan areas, public hospitals, basic insurance, mastectomy, and older age (all p < 0.001). Radiotherapy delays were also longer in metropolitan areas and after mastectomy (p < 0.001). Between 2003–2005 and 2015–2017, diagnosis-to-surgery times rose in Eastern Switzerland (from 21.3 to 31.2 days), while radiotherapy timing remained stable. Five-year overall survival improved (from 76.7% to 88.4%), but was not significantly impacted by diagnosis-to-surgery intervals. Conclusions: Despite timely surgery in Switzerland (2003–2005), disparities existed, and time to surgery increased by 2015–2017. Reducing waiting times remains important despite no significant short-term OS impact. Full article
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10 pages, 669 KiB  
Case Report
SARS-CoV-2 and HCoV IgG Antibodies in the Breast Milk of a Postpartum SARS-CoV-2 Patient Following Bamlanivimab Administration: A Case Report
by Guadalein Tanunliong, Christopher Condin, Ana Citlali Márquez, Susan Li, Nimrat Binning, Miriam Gibson, Brayden Griffiths, Alissa Wright, Deborah Money, Mel Krajden, Muhammad Morshed, Agatha N. Jassem, Gregory Haljan and Inna Sekirov
COVID 2025, 5(8), 123; https://doi.org/10.3390/covid5080123 - 1 Aug 2025
Viewed by 126
Abstract
Breast milk can provide passive immunity to infants, serving as a valuable source of maternal antibodies while remaining a non-invasive sample for investigating maternal immune responses. To date, no studies have evaluated SARS-CoV-2 and potentially cross-reactive HCoV antibodies in breast milk following bamlanivimab [...] Read more.
Breast milk can provide passive immunity to infants, serving as a valuable source of maternal antibodies while remaining a non-invasive sample for investigating maternal immune responses. To date, no studies have evaluated SARS-CoV-2 and potentially cross-reactive HCoV antibodies in breast milk following bamlanivimab administration. A 36-year-old postpartum female was PCR-positive for SARS-CoV-2 four days post-delivery. Bamlanivimab was administered intravenously two days later. Breast milk was collected before bamlanivimab infusion, daily for two weeks post-infusion, then weekly until 102 days post-infusion. Mother and infant sera were collected only at 102 days post-infusion. All milk and serum samples were tested for IgG antibodies against SARS-CoV-2 and HCoV. We observed two distinct SARS-CoV-2 antibody peaks at days 3 and 29 post-infusion, likely representing bamlanivimab transfer and the post-infection antibody response. Beta-HCoV antibodies showed two peaks at days 6 and 29, potentially representing backboosted beta-HCoV responses and/or antibody cross-reactivity with SARS-CoV-2. Infant seropositivity for SARS-CoV-2 102 days post-infusion may represent antibodies from passive transfer via breastfeeding or a subclinical infection. This case highlights the value of breast milk as a non-invasive and repeatable sample to help understand maternal immune responses post-infection, exogenous antibody infusion, and passive antibody transfer during breastfeeding, which can provide insights into maternal–infant health research. Full article
(This article belongs to the Section COVID Clinical Manifestations and Management)
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9 pages, 299 KiB  
Article
Assessing the Accuracy and Readability of Large Language Model Guidance for Patients on Breast Cancer Surgery Preparation and Recovery
by Elena Palmarin, Stefania Lando, Alberto Marchet, Tania Saibene, Silvia Michieletto, Matteo Cagol, Francesco Milardi, Dario Gregori and Giulia Lorenzoni
J. Clin. Med. 2025, 14(15), 5411; https://doi.org/10.3390/jcm14155411 - 1 Aug 2025
Viewed by 232
Abstract
Background/Objectives: Accurate and accessible perioperative health information empowers patients and enhances recovery outcomes. Artificial intelligence tools, such as ChatGPT, have garnered attention for their potential in health communication. This study evaluates the accuracy and readability of responses generated by ChatGPT to questions commonly [...] Read more.
Background/Objectives: Accurate and accessible perioperative health information empowers patients and enhances recovery outcomes. Artificial intelligence tools, such as ChatGPT, have garnered attention for their potential in health communication. This study evaluates the accuracy and readability of responses generated by ChatGPT to questions commonly asked about breast cancer. Methods: Fifteen simulated patient queries about breast cancer surgery preparation and recovery were prepared. Responses generated by ChatGPT (4o version) were evaluated for accuracy by a pool of breast surgeons using a 4-point Likert scale. Readability was assessed with the Flesch–Kincaid Grade Level (FKGL). Descriptive statistics were used to summarize the findings. Results: Of the 15 responses evaluated, 11 were rated as “accurate and comprehensive”, while 4 out of 15 were deemed “correct but incomplete”. No responses were classified as “partially incorrect” or “completely incorrect”. The median FKGL score was 11.2, indicating a high school reading level. While most responses were technically accurate, the complexity of language exceeded the recommended readability levels for patient-directed materials. Conclusions: The model shows potential as a complementary resource for patient education in breast cancer surgery, but should not replace direct interaction with healthcare providers. Future research should focus on enhancing language models’ ability to generate accessible and patient-friendly content. Full article
(This article belongs to the Section Oncology)
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17 pages, 811 KiB  
Article
Implementation of Polygenic Risk Stratification and Genomic Counseling in Colombia: An Embedded Mixed-Methods Study
by Cesar Augusto Buitrago, Melisa Naranjo Vanegas, Harvy Mauricio Velasco, Danny Styvens Cardona, Juan Pablo Valencia-Arango, Sofia Lorena Franco, Lina María Torres, Johana Cañaveral, Diana Patricia Silgado and Andrea López Cáceres
J. Pers. Med. 2025, 15(8), 335; https://doi.org/10.3390/jpm15080335 - 1 Aug 2025
Viewed by 205
Abstract
Background: Breast cancer remains a major public health challenge in Latin America, where access to personalized risk assessment tools is still limited. This study aimed to evaluate the implementation of a polygenic risk score (PRS)-based stratification model combined with remote genomic counseling [...] Read more.
Background: Breast cancer remains a major public health challenge in Latin America, where access to personalized risk assessment tools is still limited. This study aimed to evaluate the implementation of a polygenic risk score (PRS)-based stratification model combined with remote genomic counseling in Colombian women with sporadic breast cancer and healthy women. Methods: In 2023, an embedded mixed-methods observational study was conducted in Medellín involving 1997 women aged 40–75 years who underwent clinical PRS testing. The intervention integrated PRS-based risk categorization with individualized risk factor assessment and lifestyle recommendations delivered through a remote counseling platform. Results: PRS analysis classified 9.7% of women as high risk and 46% as low risk. Healthier lifestyle patterns were significantly associated with lower PRS categories (p = 0.034). Physical activity showed a protective effect (OR = 0.60, 95% CI: 0.5–0.8), while prior smoking, elevated BMI, and sedentary behavior were associated with higher risk. The counseling model achieved high delivery (93%) and satisfaction (85%) rates. Qualitative insights revealed improved understanding of genomic risk and greater engagement in preventive behaviors. Only one new case of breast cancer was detected among intermediate-risk participants, with a diagnostic lead time of 12 months. Conclusions: These findings support the feasibility, acceptability, and potential impact of integrating PRS and genomic counseling in cancer prevention strategies in middle-income settings. Full article
(This article belongs to the Special Issue Cancer Risk Assessment in Precision Medicine)
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16 pages, 343 KiB  
Article
The Relationship Between Changes in Physical Activity and Physical and Mental Health in Female Breast Cancer Survivors Undergoing Long-Term Activity Restrictions in Japan
by Naomi Tamai, Yasutaka Kimura, Ryuta Yoshizawa and Midori Kamizato
Nurs. Rep. 2025, 15(8), 279; https://doi.org/10.3390/nursrep15080279 - 30 Jul 2025
Viewed by 276
Abstract
Purpose: Exercise is recommended for survivors of breast cancer to alleviate adverse reactions and reduce the psychological burden. In recent years, however, environmental factors (e.g., pandemics and climate change) have made it difficult to exercise outdoors. Therefore, this study focused on the [...] Read more.
Purpose: Exercise is recommended for survivors of breast cancer to alleviate adverse reactions and reduce the psychological burden. In recent years, however, environmental factors (e.g., pandemics and climate change) have made it difficult to exercise outdoors. Therefore, this study focused on the COVID-19 pandemic in Japan and evaluated the relationship between changes in physical activity (PA) and mental and physical health in breast cancer survivors. Methods: A questionnaire survey was conducted among 345 outpatient female breast cancer survivors aged between 29 and 69 years. The questionnaire was based on the International Physical Activity Questionnaire, the Patient Health Questionnaire-9, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire, and the Fear of COVID-19 Scale and included patient characteristics, changes in PA during pandemic restrictions, and needs for exercise support. The analysis categorized PA changes into two groups according to activity levels. The relationship between changes in PA and physical and mental health was evaluated using logistic regression analysis. Results: Patients with decreased PA accounted for 65.5% of the study population. Regardless of their activity level, these patients were aware of an increased susceptibility to COVID-19, showed a fear of the disease and a tendency for depression, and reported low life satisfaction and declined physical function. Of the patients who stopped exercising, 82.9% reported a decline in PA. Compared with those who had never exercised, those who stopped exercising saw their risk of depression increase by 15.6%. There was a high demand for personalized exercise support from healthcare professionals. Conclusions: Regardless of their activity level, decreasing PA during the pandemic decreased mental health and physical function in breast cancer survivors. There was a higher risk of depression among patients who stopped exercising. Because it is possible that similar situations may occur in the future, interventions by healthcare professionals must be considered in order to continue exercise. Full article
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25 pages, 2761 KiB  
Article
Leveraging Deep Learning, Grid Search, and Bayesian Networks to Predict Distant Recurrence of Breast Cancer
by Xia Jiang, Yijun Zhou, Alan Wells and Adam Brufsky
Cancers 2025, 17(15), 2515; https://doi.org/10.3390/cancers17152515 - 30 Jul 2025
Viewed by 308
Abstract
Background: Unlike most cancers, breast cancer poses a persistent risk of distant recurrence—often years after initial treatment—making long-term risk stratification uniquely challenging. Current tools fall short in predicting late metastatic events, particularly for early-stage patients. Methods: We present an interpretable machine [...] Read more.
Background: Unlike most cancers, breast cancer poses a persistent risk of distant recurrence—often years after initial treatment—making long-term risk stratification uniquely challenging. Current tools fall short in predicting late metastatic events, particularly for early-stage patients. Methods: We present an interpretable machine learning (ML) pipeline to predict distant recurrence-free survival at 5, 10, and 15 years, integrating Bayesian network-based causal feature selection, deep feed-forward neural network models (DNMs), and SHAP-based interpretation. Using electronic health record (EHR)-based clinical data from over 6000 patients, we first applied the Markov blanket and interactive risk factor learner (MBIL) to identify minimally sufficient predictor subsets. These were then used to train optimized DNM classifiers, with hyperparameters tuned via grid search and benchmarked against models from 10 traditional ML methods and models trained using all predictors. Results: Our best models achieved area under the curve (AUC) scores of 0.79, 0.83, and 0.89 for 5-, 10-, and 15-year predictions, respectively—substantially outperforming baselines. MBIL reduced input dimensionality by over 80% without sacrificing accuracy. Importantly, MBIL-selected features (e.g., nodal status, hormone receptor expression, tumor size) overlapped strongly with top SHAP contributors, reinforcing interpretability. Calibration plots further demonstrated close agreement between predicted probabilities and observed recurrence rates. The percentage performance improvement due to grid search ranged from 25.3% to 60%. Conclusions: This study demonstrates that combining causal selection, deep learning, and grid search improves prediction accuracy, transparency, and calibration for long-horizon breast cancer recurrence risk. The proposed framework is well-positioned for clinical use, especially to guide long-term follow-up and therapy decisions in early-stage patients. Full article
(This article belongs to the Special Issue AI-Based Applications in Cancers)
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24 pages, 946 KiB  
Review
Long-Term Adverse Events Following Early Breast Cancer Treatment with a Focus on the BRCA-Mutated Population
by Berta Obispo, Caroline Bailleux, Blanca Cantos, Pilar Zamora, Sachin R. Jhawar, Jajini Varghese, Lucia Cabal-Hierro, Paulo Luz, Luis Berrocal-Almanza and Xiaoqing Xu
Cancers 2025, 17(15), 2506; https://doi.org/10.3390/cancers17152506 - 30 Jul 2025
Viewed by 477
Abstract
Breast cancer (BC) is the most prevalent malignancy in women worldwide. Despite most cases being diagnosed in the early stages, patients typically require a multimodal treatment approach. This typically involves a combination of surgery, radiotherapy, systemic treatments (including chemotherapy or immunotherapy), targeted therapy, [...] Read more.
Breast cancer (BC) is the most prevalent malignancy in women worldwide. Despite most cases being diagnosed in the early stages, patients typically require a multimodal treatment approach. This typically involves a combination of surgery, radiotherapy, systemic treatments (including chemotherapy or immunotherapy), targeted therapy, and endocrine therapy, depending on the disease subtype and the risk of recurrence. Moreover, patients with BC and germline mutations in the breast cancer genes 1 or 2 (BRCA1/BRCA2), (gBRCAm), who are typically young women, often require more aggressive therapeutic interventions. These mutations present unique characteristics that necessitate a distinct treatment approach, potentially influencing the side effect profiles of patients with BC. Regardless of the clear benefit observed with these treatments in terms of reduced recurrence and mortality rates, long-term, treatment-related adverse events occur that negatively affect the health-related quality of life (HRQoL) of BC survivors. Thus, long-term adverse events need to be factored into the treatment decision algorithm of patients with early BC (eBC). Physical, functional, emotional, and psychosocial adverse events can occur and represent a significant concern and a challenge for clinicians, patients, and their families. This review article provides an overview of the various long-term adverse events that patients with eBC may experience, including their associated risk factors, as well as management and prevention strategies. We also explore the evidence of the long-term impact of treatment on the HRQoL of patients with gBRCAm. By providing a comprehensive overview of current evidence and recommendations regarding patients’ HRQoL, we aim to equip clinicians with scientific and clinical knowledge and provide guidance to optimize care and improve long-term outcomes. Full article
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20 pages, 1859 KiB  
Systematic Review
From Evidence to Practice: A Systematic Review and Meta-Analysis on the Effects of Supervised Exercise on Fatigue in Breast and Prostate Cancer Survivors
by Arturo Cano-Uceda, Pablo García-Fernández, Blanca Peuyadé-Rueda, Ana María Cañuelo-Marquez, Cristian Solís-Mencía, Carmen Lucio-Allende, Luis De Sousa-De Sousa and José Luis Maté-Muñoz
Appl. Sci. 2025, 15(15), 8399; https://doi.org/10.3390/app15158399 - 29 Jul 2025
Viewed by 226
Abstract
Background: Breast and prostate cancer represent a significant global public health burden. Among the adverse effects of oncological treatments, fatigue is one of the most prevalent, persistent, and disabling symptoms. Therapeutic exercise has been shown to be effective for its management, with [...] Read more.
Background: Breast and prostate cancer represent a significant global public health burden. Among the adverse effects of oncological treatments, fatigue is one of the most prevalent, persistent, and disabling symptoms. Therapeutic exercise has been shown to be effective for its management, with supervision identified as a key factor that may enhance adherence, safety, and intensity control. This systematic review and meta-analysis aimed to compare the effects of supervised exercise programs versus usual care on cancer-related fatigue in patients with breast or prostate cancer. Methods: A systematic search (September–December 2024) was conducted in six databases (PubMed, Web of Science, Scopus, Cochrane, PEDro, Scielo), selecting RCTs from the past 10 years in English or Spanish. Studies compared supervised exercise with unsupervised exercise or usual care in stage I–III breast or prostate cancer patients within five years post-treatment. Methodological quality was assessed with the PEDro scale and risk of bias with Cochrane’s RoB 2.0. A random-effects model was used to calculate pooled effect sizes (ES, 95% CI), with heterogeneity (I2), sensitivity, subgroup, and publication bias analyses. Results: A total of 25 interventions from 19 randomized controlled trials involving over 2200 participants were included. Supervised exercise significantly reduced cancer-related fatigue compared to usual care (effect size = 0.34; 95% CI: 0.22–0.47; p < 0.001; I2 = 56%). Sensitivity analyses supported the robustness of the findings. Subgroup analyses revealed greater effects in combined exercise programs, in men, and in patients with prostate cancer. No evidence of publication bias was observed. While 73.7% of studies were rated as having good methodological quality, the risk of bias was often unclear or high. Conclusions: Supervised therapeutic exercise programs are effective and safe for reducing fatigue in breast and prostate cancer survivors. These interventions should be incorporated into comprehensive care plans, with individualization based on patients’ clinical and demographic characteristics. Further research is needed to identify the most effective and sustainable strategies for different patient subgroups. Full article
(This article belongs to the Special Issue Recent Advances in Exercise-Based Rehabilitation)
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14 pages, 1687 KiB  
Article
Bone Health and Endocrine Therapy with Ovarian Function Suppression in Premenopausal Early Breast Cancer: A Real-Life Monocenter Experience with Denosumab
by Angelachiara Rotondi, Valentina Frescura, Giorgia Arcuri, Giovanna Garufi, Letizia Pontolillo, Luca Mastrantoni, Elena Di Monte, Noemi Maliziola, Maria Antonia Fucile, Francesca Salvatori, Rita Mondello, Ilaria Poli, Gaia Rachele Oliva, Ginevra Mongelli, Antonella Palazzo, Alessandra Fabi, Emilio Bria, Giampaolo Tortora and Armando Orlandi
Curr. Oncol. 2025, 32(8), 421; https://doi.org/10.3390/curroncol32080421 - 26 Jul 2025
Viewed by 225
Abstract
Adjuvant endocrine therapy for early breast cancer significantly reduces recurrence but increases bone fragility. Given limited data on denosumab (60 mg every 6 months) in premenopausal patients receiving endocrine therapy for early breast cancer, we conducted a retrospective real-world study at the Gemelli [...] Read more.
Adjuvant endocrine therapy for early breast cancer significantly reduces recurrence but increases bone fragility. Given limited data on denosumab (60 mg every 6 months) in premenopausal patients receiving endocrine therapy for early breast cancer, we conducted a retrospective real-world study at the Gemelli Hospital (September 2018–January 2025). A descriptive analysis was performed. The primary endpoint was to assess efficacy, evaluated by changes in bone mineral density via dual-energy X-ray absorptiometry and by monitoring bone turnover markers, particularly serum C-terminal telopeptide of type I collagen. Safety was evaluated based on adverse endocrine therapy events (osteoporotic fractures) and adverse denosumab events (osteonecrosis of the jaw). Sixty-nine patients were eligible for the study. Endocrine therapy included ovarian function suppression with exemestane (89.8%) or tamoxifen (10.1%). Baseline spinal osteoporosis decreased from 20.3% to 5.8%, osteopenia from 39.1% to 34.8%, with normal T-scores rising from 17.4% to 34.8%. Femoral improvements were similar. Serum C-terminal telopeptide of type I collagen levels (evaluated in 35.8%) showed stable reduction in 97%. Denosumab adherence was 89.9%. One osteonecrosis of the jaw case occurred (1.4%); no fractures were reported. Denosumab demonstrated efficacy in improving bone density and reducing bone turnover, with excellent adherence and favorable safety. Longer follow-up is needed to assess post-discontinuation effects. Full article
(This article belongs to the Special Issue Advances in Personalized Therapy for Breast Cancer)
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15 pages, 695 KiB  
Article
Sleep Quality Moderates the Impact of Place-Based Social Adversity on Physical Health in Women with Breast Cancer Transitioning from Active Treatment to Survivorship
by Crystal L. Park, Katherine E. Gnall, Caroline Salafia and Keith M. Bellizzi
Curr. Oncol. 2025, 32(8), 420; https://doi.org/10.3390/curroncol32080420 - 26 Jul 2025
Viewed by 209
Abstract
Social adversity is linked to poorer physical health in breast cancer survivors, highlighting the urgency of addressing health equity. Simultaneously, identifying individual-level factors that mitigate these effects may provide more immediate relief for survivors. This study examined whether four modifiable psychosocial factors—emotion dysregulation, [...] Read more.
Social adversity is linked to poorer physical health in breast cancer survivors, highlighting the urgency of addressing health equity. Simultaneously, identifying individual-level factors that mitigate these effects may provide more immediate relief for survivors. This study examined whether four modifiable psychosocial factors—emotion dysregulation, physical activity, sleep disturbance, and social support—moderate the relationship between place-based social adversity and physical health in 255 breast cancer survivors (Mage = 56.03, 74.5% non-Hispanic White) within six months post-treatment. Linear regression analyses with 5000 bootstrapped estimates revealed that sleep disturbance significantly moderated the relationship between place-based social adversity and physical health (B = −0.014, SE = 0.001, bootstrapped 95% CI = −0.027, −0.001). Specifically, greater place-based social adversity was associated with poorer physical health at high levels of sleep disturbance (B = −0.22, p = 0.004), but not at low (B = 0.01, p = 0.94) or average (B = −0.10, p = 0.07) levels. Emotion dysregulation, physical activity, and social support did not moderate this relationship. Findings suggest that improving sleep quality may buffer the negative impact of social adversity on physical health, identifying sleep as a potential target for interventions aimed at reducing disparities among breast cancer survivors. Full article
(This article belongs to the Special Issue Pathways to Recovery and Resilience in Breast Cancer Survivorship)
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