Breast Cancer Research And Treatment[JOURNAL]
Sun
200 papers
Radiation treatment patterns for breast cancer brain metastases: an NCDB analysis.
Pathmarajah T, Gokun Y, Williams N … +19 more , Sizemore GM, Lefebvre H, Gatti-Mays ME, Slover B, Daniel S, Jitwatcharakomol T, Eckstein J, Andraos T, Young R, Grecula J, Raval R, Singh R, Zhu S, Blakaj D, Chakravarti A, Palmer J, Stover D, Jhawar SR, Beyer S
Breast Cancer Res Treat · 2026 Apr · PMID 42018017 · Full text
PURPOSE: Breast cancer (BC) brain metastases (BM) treatment involves radiotherapy (RT), surgery, and CNS-penetrating systemic therapies. This study evaluated treatment patterns in brain RT and corresponding survival outc...
PURPOSE: Breast cancer (BC) brain metastases (BM) treatment involves radiotherapy (RT), surgery, and CNS-penetrating systemic therapies. This study evaluated treatment patterns in brain RT and corresponding survival outcomes among patients with BC BM using the National Cancer Database (NCDB). METHODS: Patients diagnosed with BC BM between 2010 and 2021 were identified. RT was categorized as whole brain (WBRT) vs. stereotactic (SRT). We fitted Overlap Propensity Score Weighting (OPSW) Cox models to account for confounders affecting OS. Variables included age, race, ethnicity, Charlson-Deyo score, insurance, molecular subtype, facility type, and systemic therapy. RESULTS: Of 8909 patients with BC BM, 43.4% received brain RT (74.1% WBRT, 25.9% SRT). Patients that are African American, lower income, urban, triple-negative, or at community facilities were more likely to receive WBRT over SRT (p < 0.05). Median OS for the entire cohort was 10.9 months (95% CI 10.4-11.5). Systemic therapy alone (HR 0.40, 95% CI 0.36-0.43) or combined with RT (HR 0.38, 95% CI 0.35-0.42) improved OS; however RT alone did not improve survival on MVA (HR 0.96 (95% CI 0.91-1.02). Among RT recipients, SRT was associated with improved OS vs. WBRT (HR 0.76, 95% CI 0.69-0.83). Older age, comorbidities, lack of insurance, community facilities, and aggressive subtypes were associated with worse OS. CONCLUSIONS: Treatment patterns, particularly access to SRT, differ among BC BM patients therefore highlighting the need for strategies to promote equitable implementation of evidence-based guidelines. More prospective trials are also needed to establish evidence-based treatment standards for BC BM.
External validation of PREDICT Breast v3.1 for overall survival in international cohorts, including young and invasive lobular subgroups.
Verheul EM, Doornkamp F, Petrov I … +15 more , Siesling S, Lingsma HF, Koppert LB, Vreven LWA, Voogd AC, Karsten MM, Doppelbauer L, Gebert P, Kiani N, Borstnar S, Pharoah PDP, Hedayati E, Steyerberg EW, van Klaveren D, 4D PICTURE Consortium
Breast Cancer Res Treat · 2026 Apr · PMID 41991871 · Full text
PURPOSE: PREDICT Breast is an online tool that provides survival predictions for patients with early-stage breast cancer, for different treatments after surgery. External validation is essential to assess model performan...
PURPOSE: PREDICT Breast is an online tool that provides survival predictions for patients with early-stage breast cancer, for different treatments after surgery. External validation is essential to assess model performance across populations and healthcare settings. We aimed to externally validate PREDICT using clinical practice data from the Netherlands, Sweden, and Slovenia. METHODS: We validated PREDICT in national populations (Netherlands, N = 221,636; Sweden, N = 84,928) and in two specific subgroups: patients with invasive lobular breast cancer (ILC) (Netherlands, N = 26,834; Sweden, N = 10,563; Slovenia, N = 341) and patients aged ≤ 40 years (Netherlands, N = 9995; Sweden, N = 2694). We assessed discrimination with the 10-year area under the curve (AUC) and calibration of 10-year mortality predictions through calibration plots, intercepts and slopes. RESULTS: PREDICT v3.1 discriminated well in the national populations (Netherlands AUC 0.75, 95% CI 0.75-0.76; Sweden 0.75, 95% CI 0.75-0.76), with similar discrimination in ILC patients (Netherlands 0.76, 95% CI 0.74-0.76; Sweden 0.75, 95% CI 0.73-0.77; Slovenia 0.78, 95% CI 0.71-0.83). Calibration showed slight underestimation of mortality risk in the Netherlands (intercept 0.13; slope 1.01), and was near perfect in the Swedish population (intercept 0.04; slope 1.05). Amongst ILC patients, we observed some underestimation of mortality (Netherlands intercept 0.20; Sweden intercept 0.10; Slovenia intercept 0.02). In young patients, miscalibration was observed (Netherlands, intercept 0.21, slope 0.79; Sweden, intercept 0.08, slope 0.85). CONCLUSION: PREDICT v3.1 is generally well calibrated and suitable for clinical use in the evaluated European populations. Efforts to improve PREDICT should focus on more accurate predictions for younger patients.
Oral selective estrogen receptor degraders in hormone receptor-positive, HER2-negative advanced breast cancer: a systematic review and meta-analysis.
Rodrigues LLC, de Holanda Jucá Silveira L, de Almeida LFC … +9 more , de Freitas BG, Filho VOC, Noronha MM, Yabrude ATZ, Morales RG, de Melo AC, da Silva JL, Tarantino P, Batalini F
Breast Cancer Res Treat · 2026 Apr · PMID 41991764 · Publisher ↗
PURPOSE: The development of endocrine resistance is frequent in hormone receptor-positive, HER2-negative advanced breast cancer (HR + /HER2-ABC), particularly after CDK4/6 inhibitor exposure. Next-generation oral selecti...
PURPOSE: The development of endocrine resistance is frequent in hormone receptor-positive, HER2-negative advanced breast cancer (HR + /HER2-ABC), particularly after CDK4/6 inhibitor exposure. Next-generation oral selective estrogen receptor degraders (SERDs) have been developed to improve estrogen receptor blockade; however, randomized trials have yielded heterogeneous results with uncertain clinical benefit. METHODS: A PRISMA 2020 compliant systematic review and meta-analysis with PROSPERO registration was conducted. PubMed, Embase, and Cochrane CENTRAL were searched through October 2025 for phase II-III randomized trials comparing oral SERDs with standard endocrine therapy (ET) in HR + /HER2-ABC after prior ET. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Treatment effects were pooled using random effects models with prespecified subgroup analyses by ESR1 mutation status and key clinical characteristics. RESULTS: Six randomized trials, including 2808 patients, were analyzed. Oral SERDs improved PFS versus standard ET in the overall population (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.70 to 0.89). ORR was higher with oral SERDs (odds ratio [OR] 1.67; 95% CI 1.23 to 2.28), corresponding to absolute response rates of approximately 21% versus 14%. An OS improvement was observed (HR 0.72; 95% CI 0.57 to 0.90), although follow-up was limited. Benefit was concentrated in ESR1-mutated tumors (PFS, HR 0.57; 95% CI 0.48 to 0.67) with no significant PFS advantage in ESR1 wild-type disease. Gastrointestinal adverse events were more frequent with oral SERDs compared with the control ET. CONCLUSIONS: Pooled randomized evidence supports a clinically meaningful benefit of oral SERDs over standard ET after endocrine progression in HR + /HER2-ABC, with the strongest and most consistent efficacy observed in ESR1-mutated disease.
Sacituzumab-induced severe or febrile neutropenia and G-CSF utilization and cost for advanced HER2-negative breast cancer: a single-center retrospective analysis.
Tam G, Waddell D, Freeman JQ … +2 more , Chen N, Yang H
Breast Cancer Res Treat · 2026 Apr · PMID 41991763 · Full text
PURPOSE: Severe neutropenia (SN) and febrile neutropenia (FN) are clinically significant safety concerns of sacituzumab govitecan-hziy (SG). We sought to compare the rates of SN and FN from clinical trials to real-world...
PURPOSE: Severe neutropenia (SN) and febrile neutropenia (FN) are clinically significant safety concerns of sacituzumab govitecan-hziy (SG). We sought to compare the rates of SN and FN from clinical trials to real-world experience, correlate factors with SN and FN, and quantify granulocyte colony-stimulating factor (G-CSF) use in HER2-negative (HER2-) metastatic breast cancer (mBC). METHODS: We performed a retrospective analysis of patients treated with SG for advanced HER2- BC at a single US institution with a diverse patient population. The rates of SN and FN, stratified by receptor status, were compared to their respective phase III clinical trials. Multivariable logistic regression was used to evaluate factors associated with SN and FN. RESULTS: Of 87 patients treated with SG, 10 patients received primary prophylaxis. Of the 77 patients who didn't receive primary G-CSF prophylaxis, 49% and 3.9% patients developed SN and FN, respectively. SN and FN rates did not differ in the HR + /HER- mBC or mTNBC subgroups compared to clinical trials. Factors evaluated in this study were not shown to be associated with SN. Overall, 44% (38/87) required a dose interruption or reduction due to SN or FN. 11% (10/87) and 60% (52/87) received G-CSF as primary and secondary prophylaxis respectively, with a total G-CSF drug cost of $2.1 million. CONCLUSIONS: SG-induced SN and FN rates were similar to those reported in clinical trials, both in the HR + /HER- mBC and mTNBC groups. Due to small sample size, we did not identify any statistically significant risk factors of SG-associated SN. Our study provided insights into G-CSF use patterns and costs in real-world SG therapy.
In vivo exposure to CXCL12-high CAFs and chronic CXCL12 stimulation in vitro is sufficient to enhance metastasis of ER-positive breast cancer.
Miller PC, Sharma U, Tao J … +8 more , Sun J, Medina-Saenz K, Picon-Ruiz M, Morata-Tarifa C, Bare SM, Slingerland JM, El-Ashry D, Lippman ME
Breast Cancer Res Treat · 2026 Apr · PMID 41991755 · Publisher ↗
PURPOSE: Cancer-associated fibroblasts (CAFs) play important roles in breast cancer (BC) progression and metastasis. Here we investigated whether CAFs from indolent vs. aggressive BCs differ in gene expression profiles a...
PURPOSE: Cancer-associated fibroblasts (CAFs) play important roles in breast cancer (BC) progression and metastasis. Here we investigated whether CAFs from indolent vs. aggressive BCs differ in gene expression profiles and how they impact metastasis. EXPERIMENTAL DESIGN: Genotypic differences in CAF lines from basal-like (CAF23) and luminal-A BC (CAF19), were compared and effects on CAF-induced phenotypes of estrogen receptor (ER) positive BC models evaluated. RESULTS: Co-injection of MCF7 with CAF23 cells enhanced tumor metastasis in vivo, while CAF19 did not. CXCL12 was strongly overexpressed in CAF23. BC cells isolated from MCF7 + CAF23 tumors were enriched in epithelial-mesenchymal transition (EMT) genes and cancer stem cell (CSC)-like behavior. Chronic CXCL12 exposure in vitro, as may occur in BC with high CXCL12-secreting CAFs, phenocopied CAF23-enhanced metastasis. Single cell analysis of primary human BC revealed CAFs are the major source of CXCL12 in breast tumors. A high CXCL12-CAF gene expression profile was prognostic of poor BC outcome and was strongly over-represented in CAFs within BC metastases. Finally, gene expression changes induced in MCF7 cells by co-injection with CAF23 in vivo correlated significantly with gene expression differences between normal and malignant epithelial cells in BC containing high CXCL12 CAFs. CONCLUSIONS: These findings suggest that CXCL12 overexpressing CAFs can induce gene expression changes in breast cancer that promote breast cancer metastasis, potentially through expansion of the CSC population. Targeting the CAF CXCL12/CXCR4 axis may offer a novel treatment strategy for metastatic breast cancer and warrants further investigation. STATEMENT OF TRANSLATIONAL RELEVANCE: Cancer associated fibroblasts (CAF) within the breast tumor microenvironment influence breast cancer behavior. Our study indicates that high CXCL12-expressing CAFs can induce a stable metastatic phenotype in estrogen receptor positive breast cancer models. Gene expression similarities between a high CXCL12 CAF line and high CXCL12-expressing CAFs from primary and metastatic human breast cancers define a CXCL12-high CAF signature that is prognostic of poor BC patient outcome. Furthermore, gene expression changes induced in MCF7 cells by CXCL12 high CAFs in vivo were similar to the gene expression differences between normal and malignant breast epithelial cells in breast cancers containing CXCL12 high CAFs. Disruption of CAF-driven, CXCL12-mediated reprogramming of breast cancer cells might provide an opportunity to prevent or treat breast cancer metastasis.
Black and White disparity in U.S. female breast cancer mortality: a nationwide analysis, 1999-2023.
Yi H, Zhong Y, Xing D … +5 more , Wang Y, Xie S, Gao Y, Mao F, Wang X
Breast Cancer Res Treat · 2026 Apr · PMID 41991749 · Publisher ↗
OBJECTIVES: To comprehensively characterize the evolution of racial disparities in U.S. female breast cancer mortality between non-Hispanic Black and White women from 1999 to 2023 across age, geography, and urbanization...
OBJECTIVES: To comprehensively characterize the evolution of racial disparities in U.S. female breast cancer mortality between non-Hispanic Black and White women from 1999 to 2023 across age, geography, and urbanization levels. METHODS: We analyzed nationwide mortality data from the CDC WONDER database for women aged ≥ 25 years. We calculated age-adjusted mortality rates (AAMRs), absolute rate differences (ARD), and age-standardized rate ratios (ASRR). Joinpoint regression was employed to quantify temporal trends and identify significant changes over the 25-year period. RESULTS: Between 1999 and 2023, AAMRs declined for both Black (Average Annual Percent Change [AAPC] = -1.38, 95% CI -1.45 - -1.30) and White (AAPC = -1.46, 95% CI -1.56 - -1.35) women; however, Black women consistently experienced higher mortality. Disparity trends exhibited significant heterogeneity. While the mortality gap narrowed for women aged ≥ 55, the relative disparity for younger women (< 55 years) remained stagnant (ASRR ~ 1.88) despite absolute rate declines. Geographically, the Midwest achieved the most significant reduction in ARD. In contrast, the Northeast showed widening relative disparities. Notably, Massachusetts experienced a "disparity reversal," shifting from a Black survival advantage in 1999 to a significant mortality disadvantage by 2023. Additionally, disparities worsened in Large Fringe Metro areas compared to other urbanization levels. CONCLUSION: Despite national progress in reducing breast cancer mortality, racial equity remains elusive. The persistent gap among younger women and the widening disparities in specific "hotspot" regions and traditionally affluent states challenge the assumption that general healthcare improvements benefit all populations equitably, underscoring the urgent need for targeted, precision-based public health interventions.
Factors associated with and patterns of alcohol intake in late survivorship for breast cancer survivors.
Rajput S, Vierkant RA, Olson KN … +8 more , Larson NL, Stan DL, Mussallem DM, D'Andre SD, Couch FJ, Olson JE, O'Sullivan CC, Ruddy KJ
Breast Cancer Res Treat · 2026 Apr · PMID 41991748 · Full text
PURPOSE: To evaluate alcohol intake trends and identify demographic, clinical, lifestyle, and socioeconomic factors associated with alcohol consumption in late survivorship among breast cancer survivors. METHODS: Individ...
PURPOSE: To evaluate alcohol intake trends and identify demographic, clinical, lifestyle, and socioeconomic factors associated with alcohol consumption in late survivorship among breast cancer survivors. METHODS: Individuals diagnosed with stage 0-3 breast cancer enrolled in the Mayo Clinic Breast Disease registry between 2014 and 2022 reported their average weekly alcohol intake at baseline (time of diagnosis) and at approximately 4 years post-diagnosis. Alcohol intake was divided into four categories, and cross-sectional associations with demographic, clinical, and lifestyle factors were examined using Monte Carlo-based Fisher exact tests and multivariable multinomial logistic regression. Changes in alcohol consumption from baseline to Year 4 were evaluated using Bowker's test of symmetry and multinomial models. RESULTS: Among 719 participants, alcohol intake 4 years post-diagnosis closely resembled baseline patterns, with 30.2% of patients reporting no alcohol use and 48.8% of patients consuming 1-4 drinks per week. Younger age and current smoking status were strongly associated with higher intake at Year 4. Exercise and better physical health were associated with higher alcohol intake in univariable models; however, they were not in adjusted models. From time of diagnosis to Year 4, 15.6% of patients decreased their alcohol intake, 10.2% increased their alcohol intake, and 74.3% reported no change. Higher levels of mild-intensity exercise were associated with an elevation in alcohol intake over time. CONCLUSION: Alcohol consumption in late survivorship was similar to that at the time of diagnosis, after an initial decline in this cohort during early survivorship. Younger age and smoking were associated with greater Year 4 alcohol intake.
Single-cell RNA sequencing and Mendelian randomization identify context-dependent LIPA-associated classical monocyte states in sepsis and breast cancer.
Wang W, Liu M, Li X
Breast Cancer Res Treat · 2026 Apr · PMID 41991741 · Publisher ↗
BACKGROUND: Breast cancer remains one of the leading causes of cancer-related death in women, and sepsis is a major complication in cancer patients that worsens prognosis. Classical monocytes and the lysosomal acid lipas...
BACKGROUND: Breast cancer remains one of the leading causes of cancer-related death in women, and sepsis is a major complication in cancer patients that worsens prognosis. Classical monocytes and the lysosomal acid lipase gene LIPA have been implicated in immune regulation, but their roles across these two disease contexts remain incompletely understood. Here, we used single-cell RNA sequencing and Mendelian randomization to investigate context-dependent LIPA-associated classical monocyte states in sepsis and breast cancer. METHODS: We analyzed single-cell RNA sequencing datasets from breast cancer and sepsis and integrated these analyses with Mendelian randomization. Differential expression analyses were performed to identify candidate genes associated with classical monocyte states, with particular focus on LIPA. An independent single-cell RNA sequencing dataset of peripheral blood mononuclear cells (PBMCs) from patients with breast cancer was further analyzed as supportive validation. Sensitivity analyses were performed to assess the robustness of the LIPA-based classification. RESULTS: Our analyses identified LIPA-associated classical monocyte states in sepsis and breast cancer, with distinct features across disease contexts. In breast cancer, higher LIPA expression in classical monocytes was associated with features consistent with an immunoregulatory state. Independent PBMC analysis identified circulating LIPA+ classical monocytes with a broadly comparable partition pattern, suggesting that this signal may extend beyond the tumor microenvironment. Mendelian randomization provided genetic support consistent with a potential association between LIPA and breast cancer risk. Sensitivity analyses confirmed that the main observations were not dependent on a single threshold definition. CONCLUSION: Single-cell RNA sequencing and Mendelian randomization analyses support context-dependent associations between LIPA and classical monocyte states in sepsis and breast cancer. Independent PBMC analysis provides supportive evidence that the LIPA-associated signal may also be detectable in circulation. These findings should be interpreted as hypothesis-generating and provide a rationale for future paired-sample, mechanistic, and experimental studies to clarify the functional relevance of LIPA in immune regulation and breast cancer.
Topoisomerase I inhibitor antibody-drug conjugates in breast cancer: the relevance of the DNA damage response to resistance, response, and combination treatment strategies.
Wang DK, Steele JA, Opalenik SR … +1 more , Balko JM
Breast Cancer Res Treat · 2026 Apr · PMID 41991718 · Publisher ↗
INTRODUCTION: Antibody drug conjugates (ADCs) have revolutionized cancer treatment. ADCs that contain topoisomerase I inhibitors have been especially important in breast cancer treatment. Despite the substantial progress...
INTRODUCTION: Antibody drug conjugates (ADCs) have revolutionized cancer treatment. ADCs that contain topoisomerase I inhibitors have been especially important in breast cancer treatment. Despite the substantial progress brought about by these ADCs, there remains a critical need to explore combination treatment strategies to overcome resistance and enhance the efficacy of these agents. Topoisomerase I inhibitors induce DNA damage and thus activate the DNA damage response (DDR). DDR elements have been examined in terms of their role in resistance and response to topoisomerase I inhibitors, and DDR inhibitors may be especially powerful when combined with topoisomerase I inhibitors. METHODS: This review will discuss the topoisomerase I inhibitor ADCs approved for breast cancer treatment, the relevance of select components of the DNA damage response to topoisomerase I inhibitor-containing therapies, and combination strategies with inhibitors of DNA damage response, specifically focusing on inhibitors of poly (ADP-ribose) polymerase (PARP) and the ataxia-telangiectasia mutated and Rad3-related (ATR) inhibitor. CONCLUSIONS: The introduction of topoisomerase inhibitors as an ADC payload into breast cancer care has redefined a need to better understand the intricacies of their mechanism of action and tumor methods of escape and resistance, hopefully leading to novel synergistic therapeutic strategies.
Eliminating breast cancer surgery in exceptional responders: selective omission - not blind omission.
Johnson HM, Tasoulis MK, Kuerer HM
Breast Cancer Res Treat · 2026 Apr · PMID 41991708 · Publisher ↗
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Correlation between the drainage time in dynamic indocyanine green lymphography (ICG) and axillary lymph nodes metastatic involvement in breast cancer patients-a prospective study.
Anuszkiewicz K, Ekman M, Graczyk M … +3 more , Drozd M, Drucis K, Jankau J
Breast Cancer Res Treat · 2026 Apr · PMID 41991646 · Publisher ↗
PURPOSE: Axillary lymph nodes dissection (ALND) carries several complications, prompting the search for less invasive methods, especially after neoadjuvant chemotherapy. This study investigated the correlation between dy...
PURPOSE: Axillary lymph nodes dissection (ALND) carries several complications, prompting the search for less invasive methods, especially after neoadjuvant chemotherapy. This study investigated the correlation between dynamic indocyanine green (ICG) lymphography drainage time of the upper limb and the pathological stage of axillary metastatic involvement. We hypothesized that prolonged ICG drainage time correlates with higher nodal burden. METHODS: 45 female breast cancer patients undergoing ALND were enrolled. Dynamic ICG lymphography was performed the day before surgery, with intradermal injections in both upper limbs. ICG drainage time to the axillary region was recorded. Pathological and clinical lymph nodes stages (cN/(y)pN) were determined. Statistical analyses included ANOVA, t-tests, and ROC analysis were performed. RESULTS: The mean ICG drainage time was 625.6 ± 199.0 s. A statistically significant correlation was found between ICG drainage time and (y)pN stage (p < 0.05). Patients were categorized into low-burden ((y)pN0 + (y)pN1)-33 patients, and high-burden ((y)pN2 + (y)pN3) group-12 patients. Drainage time was significantly delayed in the high-burden group (525.8 ± 103.3 s vs. 900.1 ± 134.3 s; p < 0.001). No significant difference was observed between (y)pN0 and (y)pN1. ROC analysis demonstrated a high discriminatory ability for differentiating between low and high nodal burden (AUC 0.995), with an optimal cut-off of 695 s. No correlation was found with time of drainage and cN, tumor biological features, age, BMI, or arm circumference. CONCLUSION: Dynamic ICG lymphography drainage time correlates with pathological axillary nodal metastatic burden in breast cancer patients, particularly differentiating between low and high nodal involvement. This non-invasive functional assessment holds promise as a valuable adjunct for precise axillary management, guiding surgical de-escalation strategies, and potentially identifying patients at higher risk for lymphedema.
The association of an exercise and rehabilitation clinical workflow algorithm on sedentary behavior and performance status from time of breast cancer diagnosis and throughout care.
Maslana KE, Burns RD, Bai Y … +17 more , Playdon MC, Estabrooks PA, Saviers-Steiger C, Dunston ER, Galyean P, Kimball ER, Zickmund SL, Hansen PA, Ulrich CM, LaStayo PC, Steinberg D, Noren CS, Finch A', Seckinger L, Oza S, Brownson KE, Coletta AM
Breast Cancer Res Treat · 2026 Apr · PMID 41991638 · Full text
PURPOSE: Explore if a clinical workflow algorithm that connected Stage I-III newly diagnosed breast cancer (BC) patients to exercise and rehabilitation services from diagnosis throughout care associated with a lower perc...
PURPOSE: Explore if a clinical workflow algorithm that connected Stage I-III newly diagnosed breast cancer (BC) patients to exercise and rehabilitation services from diagnosis throughout care associated with a lower percentage of time spent in sedentary behavior (SB)compared with standard of care (SOC). We also examined the relationship between SB and ECOG performance status scores, a measure of functional status. METHODS: This secondary data analysis from the Comprehensive Oncology Rehabilitation and Exercise (CORE) program was carried out among 51 BC survivors (CORE = 33, SOC = 18) with evaluable wrist-worn accelerometer data. Percentage of time in SB was assessed using wrist-worn specific cut-points (Montoye) and traditional cut-points (Freedson) three times during BC care: preoperative, first postoperative visit, and 24 weeks postoperative. Repeated measures analysis of covariance tests (RM-ANCOVA; adjusted for age, cancer stage, and number of postoperative treatments) with post-hoc comparisons evaluated SB over time within and between groups. Poisson regression evaluated associations between SB and ECOG. RESULTS: Participants were mostly white (76.5%), non-Hispanic (90.2%), with mean age 58.8 ± 12.3 years, diagnosed with Stage I BC (86.3%) and had a history of more than two adjuvant treatments (56.9%), with no significant differences between groups (p > 0.05). Proportion of time spent in SB (Montoye cut-points) was 73.95% (95% CI 70.60, 77.30) preoperatively; 77.79% (95% CI 74.23, 81.35) postoperatively; and 75.05% (95% CI 71.88, 78.22) 24 weeks postoperatively, although these time effect results did not reach statistical significance in the adjusted model. A time x group interaction was observed with Freedson cut-points (mean difference: 6.15%, 95% CI 0.42, 11.88). Between preoperative and 24 weeks postoperative timepoints, pairwise comparisons indicated that CORE intervention group participants exhibited a significant increase in percentage of time in SB (mean difference: 6.09%, 95% CI 0.24, 11.93). ECOG scores at each timepoint were not associated with SB (p > 0.05). CONCLUSION: CORE program participation was not associated with reduced SB. Strategies to reduce SB should be incorporated within programs aimed at increasing physical activity engagement.
Provider level facilitators and barriers towards neoadjuvant chemotherapy for triple negative and HER2 + breast cancer: a survey of Ontario surgeons.
Ko G, Zhang E, Yee E … +8 more , Hallet J, Coburn N, Wright FC, Gandhi S, Jerzak KJ, Eisen A, Hong NJL, Roberts A
Breast Cancer Res Treat · 2026 Apr · PMID 41991619 · Publisher ↗
PURPOSE: Neoadjuvant chemotherapy (NAC) is considered standard of care for patients with cT2 + and/or N + triple negative (TN) and HER2-positive (HER2 +) breast cancer (BC). A previous retrospective study showed only 23....
PURPOSE: Neoadjuvant chemotherapy (NAC) is considered standard of care for patients with cT2 + and/or N + triple negative (TN) and HER2-positive (HER2 +) breast cancer (BC). A previous retrospective study showed only 23.9% of stage II-III TN or HER2 + BC patients in Ontario received NAC. This study aimed to identify provider-level facilitators and barriers to using NAC as first-line treatment. METHODS: We surveyed General Surgeons in Ontario using a self-administered questionnaire developed through systematic item generation and reduction. We evaluated face and content validity, as well as test-retest reliability. Surveys were sent via mail delivery with reminder. Participants could also use a QR code to access the online version. Quantitative data were analysed with descriptive statistics and qualitative responses examined using open coding. RESULTS: Total response rate was 21.1% (212/1005). All respondents who treated BC (71/71) reported being aware of indications and benefits of NAC for TNBC and HER2 + BC. Most respondents reported recommending NAC for node positive and node negative, > 2 cm TNBC (97.2%) and were equally likely for node positive HER2 + (98.6%), but less likely for node negative, > T2 (88.7%). Respondents perceived patient factors (e.g. age and comorbidities and patient's fear of chemotherapy) as barriers towards receiving NAC. The most reported facilitator to NAC was access to multidisciplinary cancer conferences. CONCLUSION: Surgeons demonstrated strong knowledge of NAC's indications and benefits, indicating that low NAC rates are likely not due to lack of awareness. Patient factors remain the major barriers to NAC uptake.
Neoadjuvant twelve weekly paclitaxel-carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer.
Leshem Y, Golomb I, Zubkov A … +5 more , Bar Y, Strulov Shachar S, Lerner S, Keren-Khadmy N, Sonnenblick A
Breast Cancer Res Treat · 2026 Apr · PMID 41963621 · Full text
PURPOSE: Standard neoadjuvant therapy for early HER2-positive breast cancer consists of 18 weeks of carboplatin, docetaxel, trastuzumab, and pertuzumab. However, treatment intensity may limit feasibility in frail patient...
PURPOSE: Standard neoadjuvant therapy for early HER2-positive breast cancer consists of 18 weeks of carboplatin, docetaxel, trastuzumab, and pertuzumab. However, treatment intensity may limit feasibility in frail patients and exceed therapeutic needs in selected early-stage disease. We report here real-world clinical outcomes of patients receiving a shortened 12-week neoadjuvant regimen of weekly paclitaxel and carboplatin administered with trastuzumab and pertuzumab (12wTCHP). METHODS: We conducted a retrospective analysis of patients with HER2-positive breast cancer treated with neoadjuvant 12wTCHP in a single tertiary medical center. RESULTS: Of forty-four eligible patients receiving 12wTCHP, 41 had invasive ductal carcinoma (IDC, 93%), and 64% were ER-positive. The majority of the cohort had stage IIA (73%, median age 59 years), while the remainder had stage IIB or stage III disease and were significantly older (median age 64 and 76 years, respectively; p = 0.007). Grade 3-4 neutropenia (20%) and diarrhea (19%) were the most frequent toxicities. No treatment-related deaths occurred. Pathological complete response (pCR) rate was 61%: 54% in ER-positive tumors and 75% in ER-negative tumors (p = 0.208). After a median follow-up of 30 months, only two recurrences (5%) were observed. None of the 30 patients with stage IIA IDC had disease recurrence. CONCLUSIONS: In this retrospective cohort study, neoadjuvant 12wTCHP was well tolerated and associated with high pCR and low early recurrence rates. These findings are hypothesis-generating and support further evaluation of de-escalated 12wTCHP regimen in selected patients.
The LIFT UP study: feasibility of systematically identifying and addressing resource needs in those with metastatic breast cancer.
Fadelu TA, Odai-Afotey A, Martin A … +15 more , Skeffington M, Hughes M, Fullem R, Revette A, Nava-Coulter B, Perilla-Glen A, Rn SB, Kusmick R, Moore A, Buck S, Sendrick K, Sammons S, Tolaney SM, Lin NU, Freedman RA
Breast Cancer Res Treat · 2026 Apr · PMID 41945184 · Publisher ↗
PURPOSE: Social determinants of health (SDOH) and health-related social needs (HRSN) impact cancer outcomes, yet few programs systematically address these needs. We examined the feasibility of routine assessment of SDOH/...
PURPOSE: Social determinants of health (SDOH) and health-related social needs (HRSN) impact cancer outcomes, yet few programs systematically address these needs. We examined the feasibility of routine assessment of SDOH/HRSN within a clinical metastatic breast cancer (MBC) program and subsequent linkage to support services. METHODS: We approached patients with MBC seen at an NCI-designated center from January-October 2023 who were ≤ 6 months from MBC consultation or diagnosis. Enrolled participants were administered a baseline survey of SDOH/HRSN, referred to appropriate services, and surveyed again at 3-6 months. Outcomes included feasibility of SDOH/HRSN documentation (defined as ≥ 80% of participants completing baseline surveys); prevalence of needs; and use of and satisfaction with support services. RESULTS: Among the 112 patients approached, 98 (87.5%) enrolled and 73 (74.5%) completed the baseline survey. Median age was 58 years (range 29-84), with 82.2%, 8.2%, and 1.4% identifying as White, Black, or Hispanic, respectively. Overall, 71.2% reported 1 + need; 28.8% had 3 + needs. Reported concerns included transportation costs (32.9%), medical costs (20.8%), medication payments (15.5%), and utility bills (19.2%); 13.7% and 6.9% reported food or housing insecurity, respectively. Although all participants needing resources were referred, 27.3% accessed referred services, and 59.1% of reported needs were partially or fully met on follow-up assessment. Patients and clinicians expressed positive feelings about the intervention. CONCLUSIONS: Our findings highlight the challenges and importance of systematically assessing SDOH/HRSN in a clinical setting, with a high degree of unmet needs reported among MBC patients. Future work will address utilization barriers and resource customization.
Alpelisib and Fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the German PRAEGNANT trial.
Hörner M, Tretschock LM, John N … +49 more , Ziegler P, Häberle L, Uhrig S, Goossens C, Amann N, Cieslik JP, Dannehl D, Deutsch TM, Dimpfl M, Ehlert M, Eichstädt K, Englisch A, Köpke MB, Krückel A, Link T, Müller A, Reinhardt K, Roth J, Schäffler H, Sych L, Tegeler CM, Wichmann C, Banys-Paluchowski M, Princk H, Rody A, Brucker SY, Ditsch N, Ettl J, Fehm T, Hack CC, Hadji P, Hein A, Janni WW, Kolberg HC, Lüftner D, Lux MP, Müller V, Schneeweiss A, Taran FA, Tesch H, Wallwiener D, Marmé F, Seitz S, Belleville E, Hartkopf A, Michel LL, Wallwiener M, Fasching PA, Tauber N
Breast Cancer Res Treat · 2026 Apr · PMID 41925922 · Full text
PURPOSE: Mutations in PIK3CA are one of several actionable mutations for patients with hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Alpelisib in combination with fulvestrant...
PURPOSE: Mutations in PIK3CA are one of several actionable mutations for patients with hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Alpelisib in combination with fulvestrant was the first approved PI3K inhibitor and was introduced in clinical practice in 2019. A lack of evidence for the use of alpelisib in the context of current treatment options like cyclin-dependent 4/6 inhibitor (CDK4/6i), highlights the importance of this analysis. We provide a real-world analysis of the use of alpelisib with the prospective German PRAEGNANT registry (NCT02338167). METHODS: 57 patients with advanced breast cancer receiving alpelisib and fulvestrant were identified. 55 Patients had received prior CDK4/6i therapy. Progression-free survival (PFS) and overall survival (OS) were calculated for all patients, and stratified according CDK4/6i pre-treatment, using the Kaplan-Meier method. Subgroups (age, line of therapy, concomitant disease among others), somatic PIK3CA mutations, reasons for discontinuation and adverse events (AEs) were analyzed. RESULTS: The median PFS was 5.0 (95% confidence interval [CI], 3.1-9.4) months, and the median OS was 20.1 (95% CI, 14.6-30.8) months. Line of therapy and concomitant diseases appeared to affect PFS, while the line of therapy and preexisting diabetes influenced OS. However, subgroups were too small for statistical testing. Discontinuation was mainly due to tumor progression (56.1%). Hyperglycemia, rash and diarrhea were the most documented AEs. CONCLUSION: This prospective real-world analysis shows slightly shorter median PFS and OS times compared with the pivotal trials. Patients in our analyses received alpelisib in later therapy lines, which may explain the poorer outcome.
Utilizing natural language processing (NLP) to identify breast cancer-associated lung metastases from pathology reports to delineate characteristics of this site of recurrence.
López JCV, Ho A, Hughes KS … +2 more , Bardia A, Vidula N
Breast Cancer Res Treat · 2026 Apr · PMID 41925896 · Publisher ↗
PURPOSE: Natural language processing (NLP, artificial intelligence) can enable automated identification of records in large datasets. The purpose of this study was to evaluate the feasibility of NLP in identifying breast...
PURPOSE: Natural language processing (NLP, artificial intelligence) can enable automated identification of records in large datasets. The purpose of this study was to evaluate the feasibility of NLP in identifying breast cancer-associated lung metastases and to understand the clinical characteristics and challenges of this common site of breast cancer recurrence. METHODS: NLP was applied to a large dataset of institutional pathology reports at an academic center to identify patients with pathologically confirmed breast cancer-associated lung metastases seen between 3/2012 and 5/2019. Chart review was conducted to confirm breast cancer-associated lung metastases and ascertain clinical and pathological features. RESULTS: Altogether, NLP identified 32 patients with pathology reports describing breast cancer-associated lung metastases from a pool of approximately 91,000 records. There was pathologic confirmation from lung biopsy tissue in the majority of cases (75%; n = 24) and from pleural fluid specimens (25% n = 8) on the remainder. After this dataset was defined using NLP, we were able to analyze clinical and pathologic features of the breast cancer-associated lung metastases. CONCLUSIONS: NLP can be applied to identify organ-specific metastases from pathology reports, such as breast cancer-associated lung metastases as done here, which can then facilitate observational, translational, and clinical research to characterize and address challenges posed by this common site of breast cancer recurrence. This cohort of patients highlights the potential application of NLP for disease characterization and clinical research in oncology.
Kidney function changes associated with trastuzumab use in women with breast cancer: a retrospective cohort study.
Molnar AO, McArthur E, Bota SE … +6 more , Stirling K, Romain J, Leong DP, Mukherjee SD, Kitchlu A, Walsh M
Breast Cancer Res Treat · 2026 Apr · PMID 41925892 · Publisher ↗
PURPOSE: Higher concentrations of human epidermal growth receptor 2 (HER2) may cause chronic kidney disease. We sought to determine if trastuzumab (a HER2 inhibitor) may be kidney protective. METHODS: Retrospective cohor...
PURPOSE: Higher concentrations of human epidermal growth receptor 2 (HER2) may cause chronic kidney disease. We sought to determine if trastuzumab (a HER2 inhibitor) may be kidney protective. METHODS: Retrospective cohort study using administrative datasets. Women from Ontario, Canada with new stage 1-3 breast cancer between April 2009 and March 2019 were included. We matched trastuzumab users (n = 6,557) 1:1 with non-users on baseline eGFR, urine albumin-to-creatinine ratio (ACR), heart failure and propensity score. Change in eGFR was examined using linear mixed models. Secondary outcomes of ≥ 30 and ≥ 40% eGFR decline, incident eGFR < 60 mL/min/1.73 m and heart failure were examined using Cox proportional hazards models. Follow-up was 3 years. RESULTS: The linear mixed model showed no significant interaction between treatment with trastuzumab and time (estimate 0.11, 95% CI -0.01 to 0.23, ml/min/1.73 m/year). There was an increased risk of ≥ 30% eGFR decline (HR 1.82, 95% CI 1.58 to 2.09), incident eGFR < 60 mL/min/1.73 m (HR 2.09, 95% CI 1.52 to 2.88) and heart failure (HR 8.07, 95% CI 5.91 to 11.02) associated with trastuzumab use at ≤ 1.5 years but not > 1.5 years. There was an increased risk of ≥ 40% eGFR decline associated with trastuzumab use at 3 months (HR 3.06, 95% CI 1.85 to 5.08) but not beyond 3 months. CONCLUSION: Trastuzumab was not associated with change in eGFR over 3 years but was associated with increased risk of ≥ 30% and ≥ 40% eGFR decline and new eGFR < 60 mL/min/1.73 m at earlier time points, potentially mediated by the increased heart failure risk observed with trastuzumab.
The impact of the COVID-19 pandemic on breast cancer screening, treatment, and overall survival.
Decker KM, Feely A, Pitz M … +7 more , Hebbard P, Kim JO, Czaykowski P, Singh H, Bucher O, Musto G, Lambert P
Breast Cancer Res Treat · 2026 Mar · PMID 41915268 · Full text
PURPOSE: We examined the association between the COVID-19 pandemic and screening, treatment, and overall survival for individuals diagnosed with breast cancer in Manitoba, Canada. METHODS: We used population-based data a...
PURPOSE: We examined the association between the COVID-19 pandemic and screening, treatment, and overall survival for individuals diagnosed with breast cancer in Manitoba, Canada. METHODS: We used population-based data and a quasi-experimental study with an interrupted time series analysis to examine the number of screening mammograms, first treatment rates, and 2-year overall survival prior to and after COVID-19 for individuals diagnosed with breast cancer. RESULTS: There was a significant decrease in screening mammograms 2 years after the start of the pandemic (ratio = 0.73%, 95% Confidence Interval (CI) 0.58, 0.89). From April to June 2020, fewer individuals diagnosed with stage I-III breast cancer had surgery (ratio = 0.59, 95% CI 0.33, 1.07). Fewer individuals diagnosed with stage I-III breast cancer had radiotherapy (RT) (ratio = 0.69, 95% CI 0.53, 0.91). RT factions per person-year were lower (ratio = 0.81, 95% CI 0.71, 0.92, April to June 2020 and 0.60, 95% CI 0.56, 0.66, July 2020 to December 2022). The proportion of individuals with stage I-III ER+ /HER2- breast cancer who had hormone therapy (HT) was lower (ratio = 0.55, 95% CI 0.36, 0.84). The proportion of individuals with stage I-III HER2+ breast cancer who had neoadjuvant chemotherapy (ratio = 3.64, 95% CI 1.18, 11.16) or targeted therapy (ratio = 3.34, 95% CI 1.13, 9.84) was higher. The proportion of individuals who had adjuvant chemotherapy (ratio = 0.14, 95% CI 0.04, 0.47, April to June 2020 and ratio = 0.19, 95% CI 0.08, 0.48, January to December 2022), targeted therapy (ratio = 0.14, 95% CI 0.04, 0.45, April to June 2020 and ratio = 0.18, 95% CI 0.07, 0.45 January to December 2022), or HT (ratio = 0.43, 95% CI 0.22, 0.83) was lower. The proportion of individuals with stage I-III triple-negative breast cancer who had neoadjuvant chemotherapy was higher (ratio = 2.92, 95% CI 1.04, 8.17). There was no difference for any treatment for stage IV breast cancers. There was no difference in 2-year overall survival for stage I-III or stage IV breast cancers. CONCLUSION: In Manitoba, Canada, there was a significant decrease in the number of screening mammograms 2 years after the start of the pandemic. Breast cancer treatment changed in accordance with updated guidelines with no impact on 2-year overall survival.
The use of endpoints in phase 3 randomized controlled trials in metastatic breast cancer.
Kupis W, Kłosowska D, Harhala M … +3 more , Sekuła M, Pogoda K, Borysowski J
Breast Cancer Res Treat · 2026 Mar · PMID 41915264 · Publisher ↗
PURPOSE: To assess the use of endpoints in phase 3 randomized controlled trials (RCTs) in metastatic breast cancer (BC). METHODS: Eligible RCTs were searched for in the WHO International Clinical Trials Registry Platform...
PURPOSE: To assess the use of endpoints in phase 3 randomized controlled trials (RCTs) in metastatic breast cancer (BC). METHODS: Eligible RCTs were searched for in the WHO International Clinical Trials Registry Platform. The impact of selected variables on the use of the primary endpoints was determined with multivariable logistic regression. RESULTS: The study included 267 phase 3 RCTs of systemic treatments, started between 2008 and 2025. The most common primary endpoint was progression-free survival (PFS; n = 228; 85.4%). It was less likely in trials of chemotherapy relative to conjugates (adjusted odds ratio [aOR], 0.10; 95% CI 0.01-0.61; p = 0.01). Among the PFS-based trials with available results (n = 107), median improvement in PFS was 2.8 months (interquartile [IQ] range, 1.35-5.75). 185/228 (81.1%) trials with PFS as the primary endpoint utilized overall survival (OS) as a secondary endpoint and 108/228 (47.4%) had quality of life (QoL) as a secondary endpoint. OS was used as the primary endpoint in only 35 trials (13.1%). It was more likely in trials enrolling patients with triple-negative BC (TNBC) relative to HER2+ BC (aOR, 5.54; 95% CI 1.57-21.93; p = 0.01). However, line of treatment did not have any statistically significant impact on the odds of OS (p > 0.05) CONCLUSION: OS as the primary endpoint has been almost completely replaced by PFS. Improvements in PFS are often modest. OS should be used as the primary endpoint more frequently, especially in TNBC and trials of later-line treatments. Moreover more trials should include QoL as a secondary endpoint.
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