Kaja E, Grupińska J, Budzyń M
… +5 more, Ciomborowska-Basheer J, Szwed A, Makałowska I, Papadovasilakis Z, Formanowicz D
Breast Cancer Res Treat
· 2026 Feb · PMID 41661346
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PURPOSE: The microbiome of the saliva can be influenced by various factors, including systemic diseases and chemotherapy. Oral dysbiosis manifests as altered bacterial composition and abundance, which often correlates wi...PURPOSE: The microbiome of the saliva can be influenced by various factors, including systemic diseases and chemotherapy. Oral dysbiosis manifests as altered bacterial composition and abundance, which often correlates with increased local and systemic inflammation. The aim of the study was to investigate the dysbiosis in the saliva of breast cancer (BC) patients before and during neoadjuvant chemotherapy (NAC). METHODS: Saliva samples were collected from 50 breast cancer patients at three timepoints (before, during, and after NAC). Saliva from 10 healthy women was used as control samples. Full-length gene 16S rRNA sequencing and analysis were performed using the Microbiome Analyst platform, R and JADBIO AutomatedML platform to compare the abundances of bacterial taxa. RESULTS: Alpha and beta diversity measures differed between breast cancer patients and healthy controls. In addition, eight bacterial genera differed significantly between breast cancer patients and controls, including Porphyromonas, Campylobacter, Oribacterium, Veillonella, and Alloprevotella. Longitudinal analysis revealed significant decrease of bacterial diversity in the course of neoadjuvant chemotherapy as well as significant change in the prevalence of a few low-abundant genera. CONCLUSIONS: The obtained results confirm BC-related and NAC-related dysbiosis in saliva, which emphasizes the potential of saliva as a diagnostic and prognostic tool in patients with breast cancer.
Breast Cancer Res Treat
· 2026 Feb · PMID 41661345
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PURPOSE: The objective of this study was to determine whether pre-existing type 2 diabetes is associated with an increased risk of breast cancer-related and all-cause mortality, compared with non-diabetes, and if the ris...PURPOSE: The objective of this study was to determine whether pre-existing type 2 diabetes is associated with an increased risk of breast cancer-related and all-cause mortality, compared with non-diabetes, and if the risk varies across glycated hemoglobin A1c (HbA1c) categories. METHODS: Using the Clinical Practice Research Datalink, we assembled a cohort of patients at least 18 years old, newly diagnosed with invasive breast cancer between 1998 and 2020, with follow-up until March 2021. Patients were followed from 3 months after breast cancer diagnosis until one of the study outcomes, end of registration with the general practice, or end of study. Multivariable Cox proportional hazards models, adjusted for 33 confounders, were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-related and all-cause mortality, comparing patients with and without type 2 diabetes among patients with and without metastatic breast cancer. In a secondary analysis, HRs for the outcomes were estimated across glycated HbA1c categories. RESULTS: The cohort included 157,298 patients with incident breast cancer. Among patients with non-metastatic breast cancer (n = 125,268), type 2 diabetes was associated with a 12% increased risk of breast cancer mortality and 21% increased risk of all-cause mortality. Among patients with metastatic breast cancer (n = 32,030), type 2 diabetes was associated with a 22% increased risk of breast cancer mortality and a 24% increased risk of all-cause mortality. The secondary analysis showed that higher glycated HbA1c was associated with an increased risk, in both the non-metastatic and metastatic cohorts. CONCLUSION: In this large population-based cohort study, type 2 diabetes was associated with a greater risk of breast cancer-related and all-cause mortality, with an increased risk among patients with type 2 diabetes in the highest glycated HbA1c categories, compared to non-diabetes.
Zhang Y, Peng J, Ma T
… +4 more, Liu X, Liu J, Zhou Q, Wang H
Breast Cancer Res Treat
· 2026 Feb · PMID 41649587
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INTRODUCTION: Triple-negative breast cancer (TNBC) is a highly aggressive subtype and lacks effective targeted therapies. Transmembrane protein 205 (TMEM205) has been implicated in tumor progression and immune resistance...INTRODUCTION: Triple-negative breast cancer (TNBC) is a highly aggressive subtype and lacks effective targeted therapies. Transmembrane protein 205 (TMEM205) has been implicated in tumor progression and immune resistance, but its precise role and mechanism in TNBC remain unclear. This study aims to explore the function and mechanism of TMEM205 in TNBC progression, as well as its impact on the tumor immune microenvironment. METHODS: The expression and prognostic significance of TMEM205 in breast cancer were analyzed using datasets, such as TCGA and UALCAN. TMEM205 was overexpressed and knocked down in TNBC cell lines (MDA-MB-231 and BT-549), and the effects on cell biological activity were verified by functional assays, including CCK-8, colony formation, wound healing, and Transwell assays. A coculture system of tumor cells and THP-1-derived macrophages was established. Key signaling molecules of TNBC cells were detected by Western blot, and cytokine levels by ELISA, so as to study tumor cell-macrophage interactions. The role of TMEM205 in tumor growth and angiogenesis was further validated through xenograft mouse models and endothelial tube formation assays. RESULTS: TMEM205 was significantly upregulated in breast cancer tissues and associated with a poor prognosis. TMEM205 overexpression promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of TNBC cells, while TMEM205 knockdown inhibited their biological functions. Furthermore, TMEM205 overexpression not only increased the secretion of IL-6 but also activated the JAK2/STAT3 signaling axis, showing a positive correlation with M2 macrophage infiltration. The TNBC cell-conditioned medium with TMEM205 overexpression significantly promoted endothelial cell angiogenesis. CONCLUSION: TMEM205, as a multifunctional oncoprotein in TNBC, jointly drives tumor progression by promoting cell proliferation, metastasis, angiogenesis, and fostering an immunosuppressive microenvironment via M2 macrophage polarization. TMEM205 may be a promising therapeutic target for TNBC.
Leblanc A, Beltran-Bless AA, Pond GR
… +15 more, El Emam K, Juwara L, Clemons L, Bayani J, Pilgram L, Pharoah P, Mallon E, Taylor KJ, Markopoulos C, Dirix L, Vandermeer L, Hilton J, Savard MF, Bartlett JMS, Clemons M
Breast Cancer Res Treat
· 2026 Feb · PMID 41642493
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BACKGROUND: Despite widespread use of clinico-pathologic and genomic risk scores in early breast cancer (EBC), questions remain as to whether they are predictive, prognostic, or both. We evaluated risk score performance...BACKGROUND: Despite widespread use of clinico-pathologic and genomic risk scores in early breast cancer (EBC), questions remain as to whether they are predictive, prognostic, or both. We evaluated risk score performance with actual patient outcomes in a trial dataset. METHODS: Discrimination and calibration of PREDICT 2.1 and PREDICT v3 for overall survival (OS) and RSClin for distant metastasis-free survival (DMFS) were compared with actual patient outcomes in 645 postmenopausal, node-negative, hormone-positive patients with EBC from the TEAM pathology substudy. Estimated chemotherapy benefit (low < 3%, moderate 3-5%, high > 5%) was also compared. RESULTS: Harrell's C-statistic for OS was 0.6893 and 0.6986 for PREDICT 2.1 and v3, and 0.6603 for DMFS using RSClin. PREDICT 2.1 underestimated and PREDICT v3 overestimated the 10-year OS. RSClin underestimated the 10-year DMFS. Of patients predicted by RSClin to derive a large benefit from chemotherapy, 44% and 99% were estimated to have a small (< 3%) benefit by PREDICT 2.1 and v3, respectively. CONCLUSION: All three scores demonstrated moderate discriminatory ability while PREDICT v3 and RSClin had better calibration. However, scores varied widely on expected benefit from chemotherapy, suggesting that RSClin is prognostic but not predictive of chemotherapy benefit. Given the cost of RSClin, further studies are required. TRIAL REGISTRATION: The trials are registered with ClinicalTrials.gov , NCT00279448, NCT00032136, and NCT00036270; NTR 267; Ethics Commission Trial 27/2001; and UMIN, C000000057.
Lee TH, Lee H, Jang JY
… +9 more, Park W, Cho WK, Cho EY, Ahn JS, Park YH, Nam SJ, Kim SW, Lee JE, Kim H
Breast Cancer Res Treat
· 2026 Feb · PMID 41642482
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PURPOSE: This study aimed to identify prognostic factors and to stratify recurrence risk using a prognostic model incorporating the identified factors in patients with residual triple-negative breast cancer (TNBC) follow...PURPOSE: This study aimed to identify prognostic factors and to stratify recurrence risk using a prognostic model incorporating the identified factors in patients with residual triple-negative breast cancer (TNBC) following neoadjuvant systemic therapy (NST). METHODS: A retrospective analysis was conducted using data from a prospectively collected single-institution database. Eligible patients had residual TNBC after NST and curative surgery between 2007 and 2020 and completed planned postoperative radiotherapy. Prognostic factors for disease-free survival (DFS) were identified using multivariable Cox proportional hazards regression. Risk groups were stratified according to the number of these factors. RESULTS: A total of 347 patients were included. With a median follow-up of 61.6 months, the 5-year DFS and overall survival rates were 62.5% and 73.9%, respectively. Lymphovascular invasion (LVI) positivity and residual cancer burden (RCB) class 3 were significant risk factors for worse DFS. The 5-year DFS rates were 82.9% (0 factor), 55.7% (1 factor), and 20.0% (2 factors) (p < 0.001). The new three-tiered stratification using LVI positivity and RCB class 3 demonstrated a higher concordance index compared to RCB class (bootstrap-estimated difference 0.038, 95% CI 0.006-0.070, p = 0.026). Adjuvant capecitabine was associated with improved 5-year DFS in patients with 1 risk factor (71.9% vs. 44.2%, p = 0.027), but not in those with 0 (83.1% vs. 81.7%, p = 0.548) or 2 factors (29.2% vs. 14.6%, p = 0.066). CONCLUSION: Patients with residual TNBC can be stratified into risk groups based on LVI and RCB class. The effect of adjuvant treatment varied across these groups. This model may support more tailored adjuvant treatment decisions after NST.
Garg G, Bharath S, Krishna A
… +5 more, Sethi S, Agrawal V, Johri G, Yadav SK, Sharma D
Breast Cancer Res Treat
· 2026 Feb · PMID 41642429
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PURPOSE: With growing interest in surgical de-escalation for breast cancer, tumor bed biopsy (TBB) after neoadjuvant chemotherapy (NACT) has been proposed as a tool to predict pathological complete response (pCR). This m...PURPOSE: With growing interest in surgical de-escalation for breast cancer, tumor bed biopsy (TBB) after neoadjuvant chemotherapy (NACT) has been proposed as a tool to predict pathological complete response (pCR). This meta-analysis assessed the diagnostic accuracy and clinical applicability of TBB in breast cancer patients achieving complete clinical response (cCR) post-NACT. METHODS: PubMed, Embase, and online clinical trial registries were systematically searched up to April 2025 for studies evaluating TBB in cCR patients after NACT. Pooled sensitivity, specificity and false-negative rate (FNR) were calculated using a random-effects model. Heterogeneity was quantified using the I statistic. RESULTS: Eight studies met inclusion criteria. Pooled sensitivity was 0.58 (95% CI 0.51-0.65), specificity was 1.00 (95% CI 0.99-1.00) and the pooled false-negative rate was (42%, 95% CI 35-49%) with I values (65.8% for sensitivity; 0% for specificity). CONCLUSION: In this meta-analysis limited to patients achieving clinical complete response after neoadjuvant chemotherapy, tumor bed biopsy demonstrated excellent specificity but suboptimal sensitivity with an unacceptably high false-negative rate. These findings indicate that a negative tumor bed biopsy cannot reliably confirm pathological complete response and therefore cannot replace standard surgical excision at present. While tumor bed biopsy may help identify residual disease, its current diagnostic performance does not support its use as a standalone tool for surgical de-escalation, underscoring the need for further refinement and prospective validation before clinical adoption.
Tiels LM, Walstra CJEF, Voogd AC
… +6 more, van der Sangen MJC, van Haren ELWG, Smidt ML, Nieuwenhuijzen GAP, Schipper RJ, Dutch Snapshot Research Group
Breast Cancer Res Treat
· 2026 Feb · PMID 41636939
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BACKGROUND: In patients with ipsilateral breast tumor recurrence (IBTR) previously treated with breast-conserving surgery (BCS) followed by radiotherapy, salvage mastectomy (SM) is still considered standard of care. Curr...BACKGROUND: In patients with ipsilateral breast tumor recurrence (IBTR) previously treated with breast-conserving surgery (BCS) followed by radiotherapy, salvage mastectomy (SM) is still considered standard of care. Currently, there is little evidence available about complication rates of repeat BCS or salvage mastectomy in patients with IBTR and possible differences. AIM: The primary aim was to report postoperative complication rates after IBTR treatment with salvage mastectomy or repeat BCS after previous BCS (± radiotherapy). Secondary, risk factors associated with complications were examined. METHODS: Complication rates were reported using descriptive statistics. Complications were classified between short-term (less than 3 months after surgery) and long-term (more than 3 months after surgery). Logistic regression was used to evaluate possible risk factors after salvage mastectomy to report an odds ratio (OR) with a 95% confidence interval (CI). RESULTS: A total of 549 cases with IBTR after primary BCS were included. Short-term complications occurred in 200 (45.2%) of 442 patients treated with salvage mastectomy and in 9 (16.4%) of 55 patients treated with repeat BCS. Seroma and surgical site infection (SSI) were most common in salvage mastectomy (31.7% and 10.9%, respectively). Long-term complications were reported in 16.7% treated with salvage mastectomy and in 14.5% with repeat BCS. The risk of short-term postoperative complications after salvage mastectomy increased significantly with higher BMI. The regression analysis showed that adjuvant radiotherapy after IBTR surgery was associated with long-term postoperative complications. CONCLUSIONS: Salvage mastectomy in case of IBTR after primary BCS is associated with high short-term complication rates, especially seroma. The risk of short-term complications after salvage mastectomy increased with increasing BMI, while adjuvant radiotherapy after salvage mastectomy is associated with long-term complications.
Reul-Hirche HM, Dunn MR, Plinsinga ML
… +3 more, Laakso EL, Troester MA, Hayes SC
Breast Cancer Res Treat
· 2026 Feb · PMID 41636913
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PURPOSE: To describe upper-body function in women after breast cancer treatment; and to explore the relationship between upper-body function, quality of life and breast cancer- related lymphoedema up to 7-years post-diag...PURPOSE: To describe upper-body function in women after breast cancer treatment; and to explore the relationship between upper-body function, quality of life and breast cancer- related lymphoedema up to 7-years post-diagnosis. METHODS: This study uses data collected in a prospective, longitudinal, population-based, breast cancer cohort study. The Disability of Arm, Shoulder and Hand questionnaire (short version -QuickDASH), the Functional Assessment of Cancer Therapy-Breast questionnaire (FACT-B) and self-report of a clinical diagnosis were used to assess upper-body function, quality of life and breast cancer-related lymphoedema, respectively, in 2,876 women with invasive breast cancer at three time points: baseline (up to 9 months post-diagnosis), and at 2- and 7-years post-diagnosis. Unadjusted cross-sectional relationships between outcomes of interest were tested at each time point. Unadjusted and adjusted regression analyses were used to explore the potential predictive relationship between upper-body function and lymphoedema. RESULTS: Upper-body impairment was common up to 7-years post-diagnosis with > 60% of women reporting at least mild impairment and 23.8-25.6% reporting moderate to very severe impairment. Impaired upper-body function at baseline assessment was associated with poorer overall quality of life (mean (standard deviation) FACT-B for no versus mild impairment: 77.5 (11.8) versus 70.9 (12.1), p < 0.05) and increased odds of breast cancer-related lymphoedema at 2 and 7 years follow-up (moderate to severe upper-body function impairment at 2- and 7- years post-diagnosis: Odds Ratio (95% Confidence interval) 2.49 (1.57, 3.93) and 2.54 (1.51, 4.26), respectively). CONCLUSION: Future research evaluating whether prospective monitoring of upper-body function and interventions that can address impairment can reduce the risk of breast cancer-related lymphoedema are warranted.
Jacquinot Q, Ennequin G, Falcoz A
… +3 more, Sawyer D, Meneveau N, Mougin F
Breast Cancer Res Treat
· 2026 Feb · PMID 41636910
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PURPOSE: Trastuzumab used for the treatment of patients with HER2-positive breast cancer induces cardiotoxicity. The NRG1/HER pathway plays a central role in human cardiovascular physiology; however, the link between exe...PURPOSE: Trastuzumab used for the treatment of patients with HER2-positive breast cancer induces cardiotoxicity. The NRG1/HER pathway plays a central role in human cardiovascular physiology; however, the link between exercise, NRG1, and cardiotoxicity is unclear. METHODS: Patients were randomized to receive adjuvant trastuzumab in combination with a training program (TG) or trastuzumab alone (CG). The aim of this study was to assess the effect of a 12-week supervised exercise training on the circulating level of NRG1. Secondary objectives were to assess the correlation between NRG1 level and cardiotoxicity. RESULTS: 89 patients were randomized (TG; n = 46; CG; n = 43), 76 have a NRG1 concentration available at baseline. After the exercise program, plasma levels of NRG1 decreased significantly in the TG (mean difference -0.20 ng/ml; 95% CI, -0.32, - 0.07) whereas they remained stable in the CG (mean difference - 0.05 ng/ml; 95% CI, - 0.20, 0.10). Notably, baseline NRG1 concentrations were higher in the TG group. However, no correlation between NRG1 changes and either cardiorespiratory fitness (V̇O max) and left ventricular ejection fraction (LVEF) was observed (R = 0.087, p = 0.53; R = -0.157, p = 0.26; and R = -0.131, p = 0.33, respectively). CONCLUSIONS: A 12-week interval training program significantly decreased NRG1 concentration in HER2-positive patients with breast cancer treated with adjuvant trastuzumab therapy, despite the trained group presenting higher baseline NRG1 values compared to the control group. In addition, this change was neither associated with V̇O max nor with LVEF. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov under the number NCT02433067.
Amburn T, Parvin-Nejad FP, Sevilimedu V
… +6 more, Zou H, Montagna G, Moo TA, El-Tamer M, Morrow M, Sacchini V
Breast Cancer Res Treat
· 2026 Feb · PMID 41636879
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BACKGROUND: Prophylactic nipple-sparing mastectomy (PNSM) is performed to prevent the development of breast cancer. Despite the increasing usage of PNSM, large-cohort, long-term follow-up data is lacking. We aim to revie...BACKGROUND: Prophylactic nipple-sparing mastectomy (PNSM) is performed to prevent the development of breast cancer. Despite the increasing usage of PNSM, large-cohort, long-term follow-up data is lacking. We aim to review a large cohort of PNSM cases to evaluate oncologic outcomes. METHODS: We retrospectively reviewed all PNSMs between 2000 and 2021 at a single institution. Clinicopathologic variables were collected and analyzed. Descriptive statistics and Kaplan Meier (KM) based survival analyses were used. RESULTS: A total of 1,255 PNSMs in 972 patients were performed from 2000 to 2021 with a median age of 43 years (IQR 37, 49) and a median follow-up of 81.3 months (IQR 50.8, 123.0). There were 38 (3.0%) cases of incidental breast cancer discovered on surgical pathology. There were 3 (0.3%) new primary breast cancer occurrences after PNSM. The KM estimates for 5-year rates in the entire cohort (n = 972) of incidence of new breast cancer, breast cancer-related mortality, and overall mortality were as follows: 0.15% (95%CI 0, 0.44%), 0.93% (95%CI 0.28%, 1.57%), and 1.63% (95%CI 0.78%, 2.48%), respectively. The KM estimates for 5-year rates in the BRCA-only cohort (n = 333) of incidence of new breast cancer, breast cancer-related mortality, and overall mortality were as follows: 0.44% (95%CI 0, 1.30%), 1.75% (95%CI 0.21%, 3.26%), and 2.09% (95%CI 0.42%, 3.73%), respectively. CONCLUSION: New primary breast cancer infrequently developed after PNSM in this study. Incidental breast cancer was identified on surgical pathology in a small subset of patients. PNSM may be associated with preventing breast cancer development.
Chun S, Lee HR, Jung JH
… +4 more, Kim SH, Cho IY, Han K, Shin DW
Breast Cancer Res Treat
· 2026 Feb · PMID 41636872
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PURPOSE: Obesity and low muscle mass (LMM) have been associated with adverse outcomes in cancer population. However, their individual and combined effects on long-term mortality and cardiovascular disease (CVD) outcomes...PURPOSE: Obesity and low muscle mass (LMM) have been associated with adverse outcomes in cancer population. However, their individual and combined effects on long-term mortality and cardiovascular disease (CVD) outcomes in breast cancer patients are not well characterized. METHODS: We conducted a retrospective study of 46,037 women aged 40 years and older with pathologically confirmed breast adenocarcinoma using data from the Cancer Public Library Database. LMM was defined as the lowest quartile of appendicular skeletal muscle mass index (ASMI), estimated by a validated equation. The remaining quartiles were classified as normal muscle mass (NMM). Obesity was defined as BMI ≥ 25 kg/m. Patients were categorized into four groups by muscle mass and obesity status. Multivariable Cox proportional hazards models assessed associations with overall, cancer-specific, and cardiovascular mortality, and incident CVD. RESULTS: Over a mean follow-up of 4.63 years, 2,286 deaths and 851 incident CVD events were recorded. Compared to NMM, LMM was independently associated with increased overall (adjusted hazard ratio [aHR] 1.27, 95% CI 1.15-1.40), cancer-specific (aHR 1.19, 95% CI 1.08-1.32), and cardiovascular (aHR 1.76, 95% CI 1.10-2.81) mortality. When stratified by muscle-obesity status, the LMM with obesity group had the highest risk of overall (aHR 1.69, 95% CI 1.18-2.42) and cancer (aHR 1.58, 95% CI 1.03-2.43) mortality. LMM without obesity was also associated with increased overall, cancer, and cardiovascular mortality. CONCLUSIONS: LMM was independently associated with increased mortality in breast cancer patients, with risk amplified in those with coexisting obesity.
Chen Y, Wang R, Wu L
… +6 more, Li J, Yang M, Qi X, Wang M, Wang Y, Li Q
Breast Cancer Res Treat
· 2026 Feb · PMID 41627574
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BACKGROUND: With the rising survival rates of breast cancer, fertility preservation has become a paramount concern for young patients throughout their anticancer treatment. We conducted a systematic review to assess and...BACKGROUND: With the rising survival rates of breast cancer, fertility preservation has become a paramount concern for young patients throughout their anticancer treatment. We conducted a systematic review to assess and synthesize evidence and recommendations on fertility preservation in breast cancer patients to provide evidence-based clinical guidance. METHODS: According to the '6S' evidence resource model, evidence retrieval is searched from the top-down and collected relevant clinical decisions, guidelines, evidence summaries, expert consensus, recommended practices, and systematic reviews. The retrieval time limit was from the database establishment to July 2025. Two reviewers independently screened and evaluated the literature, and then extracted and summarized the evidence according to the JBI grading of evidence and recommendation system. RESULTS: A total of 47 publications were finally included, including 14 guidelines, 9 expert consensus, 7 recommended practices, and 17 systematic reviews. Through the induction and integration of the evidence, the evidence was finally summarized from ten aspects: treatment-related factors for fertility impairment, risk assessment of fertility impairment, genetic risk assessment and intervention, fertility preservation counseling and management, target population for fertility preservation, fertility preservation protocols, surgical treatment and fertility, post-treatment pregnancy management, post-treatment breastfeeding management and contraceptive management, and totally 50 best available evidence were formed. CONCLUSIONS: This study summarized the best available evidence for fertility preservation in breast cancer patients from ten aspects, which can provide guidance for clinical medical staff to develop individualized fertility preservation plans and assist patients in making fertility preservation decisions, ultimately supporting young breast cancer patients in achieving the dual goals of survival and future parenthood.
Rojas DP, Frassoni S, Maisonneuve P
… +18 more, Intra M, Kouloura A, Zerella MA, Fodor CI, Cornacchia L, Bergamaschi L, Sangalli C, Comi S, Morra A, Dicuonzo S, Galimberti V, Veronesi P, Zaffaroni M, Vincini MG, Bagnardi V, Orecchia R, Jereczek-Fossa BA, Leonardi MC
Breast Cancer Res Treat
· 2026 Jan · PMID 41615490
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PURPOSE: The study aims to develop and validate a predictive tool for assessing the risk of in-breast tumor recurrence (IBTR) in breast cancer patients considered candidates for intraoperative radiotherapy using electron...PURPOSE: The study aims to develop and validate a predictive tool for assessing the risk of in-breast tumor recurrence (IBTR) in breast cancer patients considered candidates for intraoperative radiotherapy using electrons (IOERT). METHODS: This study included 3397 breast cancer patients treated with IOERT at a single institution between 2000 and 2016. The primary endpoint was IBTR, with or without nodal or distant metastasis. Fine and Gray regression models were used to identify predictors of IBTR. A nomogram predicting the 5- and 10-year probability of IBTR was developed based on the multivariable model and was validated both internally and externally using data from the IOERT arm of the ELIOT phase III trial (585 patients). RESULTS: With a median follow-up of 6.1 years (interquartile range 4.3-8.0), 265 IBTRs (7.8%) were observed, resulting in an IBTR cumulative incidence of 4.4% (95% CI 3.7-5.2) at 5 years and 13.5% (95% CI 11.7-15.5) at 10 years. Multivariable analysis revealed that age under 60, certain histologic subtypes, positive axillary nodes, and intermediate/high tumor grade were key risk factors for IBTR. The overall Harrell's concordance statistic was 0.69 (95% CI 0.66-0.73) in the internal and 0.64 (95% CI 0.57-0.71) in the external validation. CONCLUSION: The nomogram has demonstrated moderate discriminative ability in predicting IBTR in the internal validation set and may be a useful tool to support treatment decision-making in breast cancer patients eligible for IOERT.
Ricceri F, Favaro E, Catalano A
… +13 more, Gilcrease GW, Calabrese SC, Ferracin E, Di Cuonzo D, Macciotta A, Dansero L, d'Errico A, Franco P, Numico G, Gnavi R, Costa G, Pagano E, Sacerdote C
Breast Cancer Res Treat
· 2026 Jan · PMID 41609957
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PURPOSE: Breast cancer (BC) is a leading public-health issue affecting women on a global scale. Thanks to the widespread implementation of screening programs and the improvement in therapies, women with BC live longer bu...PURPOSE: Breast cancer (BC) is a leading public-health issue affecting women on a global scale. Thanks to the widespread implementation of screening programs and the improvement in therapies, women with BC live longer but they also are more likely to experience an increased risk of other diseases. Reasons for this increased risk include genetics, shared risk factors, and adverse effects from BC treatment. Therefore, this research aimed to analyse the risk of myocardial infarction (MI) and stroke in women with BC, considering the potential side effects of treatments. METHODS: For the analysis, we used data coming from the Piedmont Longitudinal Study (PLS), an administrative cohort based on the record-linkage among census data and several health-administrative databases involving more than 4 million inhabitants. The study population comprised women aged 30-75 years from the PLS study, excluding those with myocardial infarction or stroke at baseline. To analyse the investigated associations, competing risk analyses were performed, through the Cause-Specific Proportional Hazards model. RESULTS: Among 1,342,333 women ranging from 30 to 75 years old, 19,203 had a BC diagnosis, of whom 206 (1.1%) experienced a subsequent MI and 203 (1.1%) a stroke. Women with BC showed an increased risk for MI (HR: 1.20; 95% CI 1.05-1.38) and for stroke (HR: 1.58; 95% CI 1.38-1.82). Chemotherapy was observed to be the major risk factor for MI in BC women, while no different risk by therapy was found for stroke. CONCLUSION: The results supported the hypothesis about the toxic effect of BC therapies, suggesting that clinicians should routinely and actively screen for treatment-related toxicities in women with BC and that researchers should prioritize personalized treatments to minimize potentially devastating side effects.
Leggat-Barr K, Lewis T, Tice JA
… +21 more, Tsopurashvili E, Sayaman R, Warner P, Malvin K, Sabacan L, Perry-Solomon A, Theiner S, Acerbi I, Griffin A, McGuire J, Lee V, Borowsky AD, Wisdom Study and Athena Breast Health Network Investigators and Advocate Partners, Eklund M, Kaplan C, Hiatt RA, Fiscalini AS, Kerlikowske K, Shieh Y, Esserman L, Van't Veer L
Breast Cancer Res Treat
· 2026 Jan · PMID 41604043
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PURPOSE: Determine the association between the Breast Cancer Surveillance Consortium v2 model (BCSC) risk score and advanced and non-advanced invasive breast cancer (IBC). METHODS: We estimated BCSC 5-year invasive breas...PURPOSE: Determine the association between the Breast Cancer Surveillance Consortium v2 model (BCSC) risk score and advanced and non-advanced invasive breast cancer (IBC). METHODS: We estimated BCSC 5-year invasive breast cancer risk for 11,915 participants in a prospective screening cohort with median follow-up of 6.9 years prior to breast cancer diagnosis. Individuals in the top 25% by age of BCSC risk standard were considered high-risk, those in the bottom 75% low-risk. We obtained cancer outcomes, including American Joint Committee on Cancer (AJCC) prognostic pathologic stage, from the San Francisco Mammography Registry and an institutional cancer registry. We examined the associations of BCSC risk scores with advanced (≥ AJCC prognostic stage II) and non-advanced (AJCC prognostic stage I) IBC using Fisher's exact test and logistic regression. RESULTS: Of 11,915 participants, 4,005 (34%) were high-risk. There were 254 incident IBC cases, of which 40 (16%) were advanced and 214 (84%) were non-advanced. The median 5-year BCSC risk score for women with and without IBC was 1.83% and 1.45%, respectively (p < 0.001). High BCSC risk among women diagnosed with breast cancer was associated with non-advanced cancer (OR = 2.25, 95% CI = 1.71-2.95, p < 0.0001), but not with advanced cancer (OR = 1.20, 95% CI = 0.63-2.29, p = 0.57) compared to women not diagnosed with breast cancer. CONCLUSION: High BCSC risk scores were associated with high rates of non-advanced IBC. As non-advanced cancers are more likely to be hormone receptor-positive, BCSC may optimally identify candidates for endocrine risk reduction.
Lammers EMJ, Beens-van Dijk J, Nijdam A
… +7 more, Menezes R, Schaapveld M, Krul IM, Obdeijn IM, van Leeuwen FE, So-Osman C, Aleman BMP
Breast Cancer Res Treat
· 2026 Jan · PMID 41604023
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PURPOSE: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) before the age of 40 years face increased breast cancer (BC) risk. Dutch guidelines recommend annual magnetic resonance imaging (MRI) a...PURPOSE: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) before the age of 40 years face increased breast cancer (BC) risk. Dutch guidelines recommend annual magnetic resonance imaging (MRI) and mammography at ages 30-60 years starting eight years after RT. Dual-modality screening is burdensome and may increase false positive rates. We therefore compared the diagnostic value of each individual modality with MRI and mammography combined. METHODS: Results of dual-modality BC screenings performed in 2005-2021 at two Dutch survivorship clinics were used to estimate sensitivity and specificity for each modality and MRI and mammography combined. RESULTS: We retrospectively reviewed 550 screening rounds in 134 HL survivors (median follow-up: 3 years) during which 19 early-stage tumors occurred. Sensitivity was 79% (95% Confidence Interval (CI): 54-94) for MRI alone, 63% (95% CI: 38-84) for mammography alone and 95% (95% CI: 74-100) for both modalities combined. Specificity was 89% (95% CI: 86-91) for MRI alone, 97% (95% CI: 95-98) for mammography alone and 86% (95% CI: 83-89) when combining modalities. Additional ultrasound was performed in 15.3% of screening rounds (in 74.4% due to MRI findings) and puncture/biopsy in 8.0%. CONCLUSIONS: In conclusion, to obtain a sufficiently high screening sensitivity in female HL survivors treated with chest RT, we recommend screening with both MRI and mammography. However, MRI is associated with a high false positive rate. Our findings inform survivors and clinicians about effectiveness of BC screening and its burden.
Lavigne O, Poumeaud F, Reverdy T
… +10 more, Huynh VT, Roces G, Poupin G, Gouillou M, Bobrie A, Donadille E, Dalenc F, Jacot W, Robert J, Fiteni F
Breast Cancer Res Treat
· 2026 Jan · PMID 41591534
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PURPOSE: The standard first-line treatment for patients with hormone receptor-positive (HR +) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer is cyclin-dependent kinase 4/6 (CDK4/6) inh...PURPOSE: The standard first-line treatment for patients with hormone receptor-positive (HR +) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer is cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy (ET). Optimal therapy after CDK4/6 inhibitors remains to be determined. We aimed to define the appropriate second-line treatment after CDK4/6 inhibitors in a real-life population. METHODS: Patients who had received CDK4/6 inhibitors with aromatase inhibitors (AIs) for HR + /HER2- metastatic breast cancer were included from March 2017 to May 2021 at five French cancer centers.The primary objective was to describe second-line treatment after primary treatment with CDK4/6 inhibitors plus AIs. RESULTS: We included 381 patients who received CDK4/6 inhibitors combined with AIs as first-line therapy. Patients with progressive disease (N = 165) benefited from a second-line of treatment: 69 (41.8%) were treated with chemotherapy, while 90 (54.6%) received endocrine therapy (ET alone: 59, 35.8%; ET plus targeted therapy: 31, 18.8%).Patients on chemotherapy were younger compared to those receiving ET (p = 0.011). Patients experiencing earlier progression were more likely to benefit from chemotherapy than ET (p = 0.001). Patients with visceral disease at diagnosis were more often treated with chemotherapy. Second-line median PFS was 6.4 months (95% CI [5.0-12.9]) for chemotherapy and 8.4 months (95% CI [5.4-11.7]) for ET ± targeted therapy, with no significant difference (HR 1.08, 95% CI [0.73-1.59], p = 0.70). CONCLUSION: This French real-world study demonstrates limited progression-free survival benefits across all second-line strategies after CDK4/6 inhibitor progression, highlighting an urgent clinical need for more effective post-progression therapies.
Wang Q, Van Alsten SC, Ji X
… +7 more, Salim E, Salazar N, Scott JE, Yang X, Onyenwoke RU, Troester MA, Williams KP
Breast Cancer Res Treat
· 2026 Jan · PMID 41569442
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PURPOSE: Inflammatory breast cancer (IBC) has been hypothesized to represent a distinct molecular subtype. However, few IBC-specific gene expression patterns have been identified, and previous genomic studies of IBC have...PURPOSE: Inflammatory breast cancer (IBC) has been hypothesized to represent a distinct molecular subtype. However, few IBC-specific gene expression patterns have been identified, and previous genomic studies of IBC have been small with limited information on social determinants. METHODS: We identified 153 IBC cases in the Carolina Breast Cancer Study (total N = 4,739). RNA expression was measured on the NanoString platform (N = 74 IBC, 2,696 non-IBC) and used to determine molecular subtypes, including PAM50, immune, homologous recombination deficiency (HRD), and P53 status. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of associations between IBC and patient demographic, molecular, and social characteristics using logistic regression, and compared differences in gene expression using ANOVA. RESULTS: Women with IBC were associated with Black and under 50 compared to non-IBC. IBC was associated with rural address (OR = 1.53) and poverty (OR = 1.61). Molecularly, IBC was associated with HER2-enriched (OR = 6.14), Luminal B (OR = 2.90), P53 Mutant-like (OR = 1.79), and high HRD (OR = 1.90). Neither adiposity nor immune subtype was significantly associated with IBC. Only six of 219 genes measured were significantly differentially expressed between IBC and non-IBC, including HER2-related (ERBB2, FGFR4, GRB7) and P53-related genes (BTG2, LOC400043, MAP2K4). CONCLUSION: Although not associated with immune subtypes, IBC showed differences in HER2 and P53 pathways. The association of IBC with rurality and poverty underscores the importance of health care access for timely diagnosis and treatment of IBC.
Pedersini R, Moretti L, Laganà M
… +16 more, Schivardi G, Baluta V, Zamparini M, Conforti E, Ravanelli M, Brentegani C, Amoroso V, Grisanti S, Buizza C, Scartabellati G, Bazzoli M, Ippolito G, Pellicioli F, Farina D, Berruti A, Cosentini D
Breast Cancer Res Treat
· 2026 Jan · PMID 41557073
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PURPOSE: Investigate skeletal morbidity (SM) in metastatic breast cancer (MBC) patients undergoing CDK4/6 inhibitors (CDK4/6is) and endocrine therapy (ET). METHODS: In this retrospective study we evaluated skeletal morbi...PURPOSE: Investigate skeletal morbidity (SM) in metastatic breast cancer (MBC) patients undergoing CDK4/6 inhibitors (CDK4/6is) and endocrine therapy (ET). METHODS: In this retrospective study we evaluated skeletal morbidity - defined as the occurrence of skeletal-related events (SREs) in metastatic bone and fragility fractures in non-metastatic bone - in 214 MBC patients who had received ET and CDK4/6is. As secondary aim, we compared VF progression, defined as a new fracture or worsening of a pre-existing fracture at spine CT scan, between 121 patients receiving ET alone (cohort A) and 121 patients on ET plus CDK4/6is (cohort B), balanced using propensity score. RESULTS: Among the 147 patients (68.7%) with bone metastases, 59 (40.1%) experienced SREs including non-vertebral pathologic fractures (17 patients, 11.6%), pathologic VF progression (21 patients, 14.3%), spinal cord compression (3 patients, 2.0%), radiation to bone (18 patients, 12.2%). Considering the non-metastatic bone, 3 out of 214 patients (1.4%) experienced new non-vertebral fragility fractures, and 26 patients (12.2%) had fragility VF progression. In the comparative study, pathologic VF progression in metastatic bone was 38.3% in cohort A and 29.1% in cohort B (p = 0.093). The corresponding fragility VF progression rate in non-metastatic bone was 22.3% and 12.4% (p = 0.031). CONCLUSIONS: A considerable proportion of women with MBC treated with CDK4/6is + ET experience SM on both metastatic and non-metastatic bone. Patients treated with CDK4/6is + ET had lower SM than those on ET alone.