Breast Cancer Research And Treatment[JOURNAL]
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200 papers
OPERA: a phase II study of DHP107 (oral paclitaxel) versus intravenous paclitaxel in patients with HER2-negative recurrent or metastatic breast cancer.
Rugo HS, Pluard TJ, Sharma P … +8 more , Melisko M, Al-Jazayrly G, Ji Y, Vidula N, Ellerton J, Smakal M, Zimovjanova M, Weng D
Breast Cancer Res Treat · 2026 Mar · PMID 41910867 · Full text
PURPOSE: DHP107 is an oral paclitaxel enabling administration of paclitaxel without Cremophor EL, a vehicle used to improve the solubility of intravenous (IV) paclitaxel. The randomized phase II OPERA study investigated...
PURPOSE: DHP107 is an oral paclitaxel enabling administration of paclitaxel without Cremophor EL, a vehicle used to improve the solubility of intravenous (IV) paclitaxel. The randomized phase II OPERA study investigated the efficacy and safety of DHP107 versus IV paclitaxel in patients with HER2-negative breast cancer. METHODS: OPERA was conducted in the USA and Czech Republic. Patients were ≥ 18 years, with measurable disease, and histologically or cytologically confirmed recurrent or metastatic breast cancer with any tumor hormone receptor status. Patients were randomized 2:1 to DHP107 (200 mg/m po bid with premedication if needed on days 1, 8, and 15, every 28 days) or IV paclitaxel (80 mg/m with standard premedication on days 1, 8, and 15 every 28 days). The primary objective was DHP107 efficacy; secondary objectives included DHP107 safety and tolerability. RESULTS: 72 patients were randomized, 48 to DHP107 and 24 to IV paclitaxel. There was one complete response and 11 partial responses with DHP107 (objective response rate [ORR 25.0%; 90% CI 15.1-37.3), and six partial responses with IV paclitaxel (objective response rate [ORR] 28.6%; 90% CI 13.2-48.7; p = 0.7559). Median progression-free survival (PFS) was 5.5 months for DHP107 and 4.7 months for IV paclitaxel (p = 0.8018); median overall survival (OS) was 17.1 and 13.2 months, respectively (p = 0.7629). Common all-grade adverse events were diarrhea (68.8%), nausea (64.6%), and fatigue (52.1%) for DHP107 and fatigue (47.6%), peripheral neuropathy (42.9%), and alopecia (42.9%) for IV paclitaxel. CONCLUSION: DHP107 is a tolerable and feasible treatment for patients with recurrent or metastatic HER2-negative breast cancer, with similar efficacy and safety to IV paclitaxel. CLINICALTRIALS: gov no: NCT03326102; date of registration October 19, 2017.
Adjuvant capecitabine in women with triple-negative breast cancer with residual disease after carboplatin-containing neoadjuvant chemotherapy.
Tavares GM, Ramalho SOB, da Silva LR … +4 more , Telles GD, de Paiva Silva GR, Torresan RZ, Derchain SFM
Breast Cancer Res Treat · 2026 Mar · PMID 41910838 · Full text
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by early relapse and limited therapeutic options. Carboplatin added to anthracycline/taxane neoadjuvant chemotherapy (NACT) raises p...
BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by early relapse and limited therapeutic options. Carboplatin added to anthracycline/taxane neoadjuvant chemotherapy (NACT) raises pathologic complete response (pCR) rates. The role of adjuvant capecitabine following NACT containing carboplatin remains unclear, particularly in real-world settings. METHODS: Data of patients who were diagnosed with TNBC and received NACT at CAISM/UNICAMP (2017-2023), followed up until June 2025 were analyzed retrospectively. The cohort study included 184 women with TNBC treated with anthracycline, taxane, and carboplatin-based NACT. Clinical, pathological, and treatment data were collected from institutional databases and the CAISM Biobank. Survival outcomes were analyzed according to pCR and use of adjuvant capecitabine among patients with non-pCR. Median follow-up was estimated using the reverse Kaplan-Meier method. Additional exploratory analyses included stratification by Residual Cancer Burden (RCB-I vs RCB-II/III), multivariable Cox models including capecitabine as the exposure variable, and administrative censoring sensitivity analyses at 36 and 48 months. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared with log-rank tests; multivariable Cox models assessed prognostic factors. RESULTS: Among 184 women, pCR was achieved in 40% and was associated with younger age, earlier clinical stage and high histologic grade. Survival outcomes were significantly better for patients with pCR, with an approximately 85-87% reduction in the risk of recurrence and death compared with non-pCR. Among the 111 patients with residual disease, 44 received adjuvant capecitabine. Adjuvant capecitabine did not improve DFS (HR = 0.96; 95% CI 0.52-1.78) or OS (HR = 0.70; 95% CI 0.33-1.46) in univariable analyses. In multivariable models stratified by capecitabine use, Ki-67 remained the only independent prognostic factor slightly associated with worse DFS, while capecitabine showed no significant effect. CONCLUSIONS: In this real-world cohort, achieving pCR after carboplatin-containing NACT was the strongest determinant of favorable prognosis. Adjuvant capecitabine was not associated with statistically significant improvement in survival outcomes. The role of capecitabine following prior platinum exposure remains uncertain and warrants further investigation.
Real-world treatment patterns and outcomes in older patients with metastatic breast cancer: a multi-institutional retrospective cohort study.
Mitsueda R, Sagara Y, Niikura N … +7 more , Ohno S, Taira T, Takada M, Miyashita M, Ishiguro H, Saji S, Masuda N
Breast Cancer Res Treat · 2026 Mar · PMID 41903009 · Publisher ↗
BACKGROUND: As populations age worldwide, breast cancer mortality among older patients continues to rise despite therapeutic advances. This study investigates differences in treatment patterns and outcomes between older...
BACKGROUND: As populations age worldwide, breast cancer mortality among older patients continues to rise despite therapeutic advances. This study investigates differences in treatment patterns and outcomes between older and younger patients with metastatic breast cancer. METHODS: We analyzed clinical data from the Advanced Breast Cancer Database (ABCD) maintained by the Japanese Breast Cancer Research Group. The dataset included patients registered between June 1, 2020, and October 31, 2023, encompassing clinicopathologic information, treatment details, breast cancer specific survival (BCSS), and overall survival (OS). RESULTS: A total of 1629 patients were included. The frequency of chemotherapy and genomic testing decreased with age, yet patients in their 70 s demonstrated treatment durations and survival outcomes comparable to those of younger patients. In contrast, patients aged ≥ 80 years exhibited shorter duration of second-line therapy (adjusted HR:0.65, 95% CI: 0.43-1.04) and poorer OS (adjusted HR:0.62, 95% CI: 0.37-1.04) and BCSS (adjusted HR:0.66, 95% CI: 0.38-1.14), despite most deaths being attributable to breast cancer rather than non-cancer-related causes. CONCLUSIONS: This multicenter retrospective study demonstrates that patients in their 70 s can achieve comparable benefits from systemic therapy to younger individuals, emphasizing the importance of not withholding treatment based solely on chronological age. Conversely, the limited effectiveness of later-line therapies in patients aged ≥ 80 highlights the need for individualized treatment strategies that balance efficacy, quality of life, and comorbidities through comprehensive geriatric assessment and shared decision-making.
Cost-effectiveness of DPYD genotyping prior to capecitabine administration for metastatic breast cancer.
Chiddarwar T, Blaes A, Kuntz K
Breast Cancer Res Treat · 2026 Mar · PMID 41902937 · Full text
PURPOSE: Patients with a DPYD genetic deficiency who receive capecitabine are at increased risk of severe, potentially fatal toxicities due to impaired drug metabolism. Genetic testing for this deficiency allows for proa...
PURPOSE: Patients with a DPYD genetic deficiency who receive capecitabine are at increased risk of severe, potentially fatal toxicities due to impaired drug metabolism. Genetic testing for this deficiency allows for proactive dose adjustments to mitigate these risks. We evaluated the cost-effectiveness of DPYD genotyping prior to capecitabine administration, followed by dose modification for patients with metastatic breast cancer. METHODS: We developed a state-transition model to simulate health outcomes and costs for a cohort of 62-year-old women with metastatic breast cancer from the perspective of the U.S. healthcare payer. Costs and utilities were derived from the literature to calculate quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for DPYD genotyping compared to no DPYD genotyping. We conducted deterministic and probabilistic sensitivity analyses to identify factors influencing cost-effectiveness. RESULTS: The genotyping strategy was cost-effective, with a cost of $2,832 yielding 1.16 QALYs, compared to $2,677 and 1.15 QALYs for the no-genotyping strategy. This resulted in an ICER of $12,916/QALY and $10,333 per life-year-gained. In probabilistic sensitivity analysis, the genotyping strategy was cost-effective in 99% of the simulations, using a willingness-to-pay threshold of $100,000/QALY. Results from scenario analyses testing key assumptions also showed that genotyping is cost-effective. CONCLUSION: Our findings support the implementation of DPYD genotyping prior to capecitabine initiation in metastatic breast cancer patients. This strategy exemplifies the value of personalized medicine and pharmacogenomics in improving treatment safety and effectiveness. As sequencing technologies advance and become affordable, integration of genotyping into routine oncology care is increasingly feasible.
Development and validation of a highly accurate multigene gene expression biomarker to predict chemotherapy response in primary triple-negative breast cancer.
Amniouel S, Jafri MS
Breast Cancer Res Treat · 2026 Mar · PMID 41885969 · Full text
PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen and progesterone receptors and HER2 amplification. Representing 10-15% of breast cancer cases, TNBC disproportionately affects Black...
PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen and progesterone receptors and HER2 amplification. Representing 10-15% of breast cancer cases, TNBC disproportionately affects Black and pre-menopausal women and is associated with poorer outcomes. With chemotherapy as the primary systemic treatment option, achieving a pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) is a key prognostic factor. However, TNBC biological heterogeneity complicates treatment response prediction. This study aimed to identify transcriptomic biomarkers predictive of NAC response in TNBC patients and evaluate machine-learning models for response classification. METHODS: We performed transcriptomic profiling on tumors from 234 TNBC patients, divided into training 138 pCR,72 residual disease (RD) and test 9 pCR, 15 RD cohorts. Feature selection was conducted using LASSO regression and Boruta algorithms to identify robust biomarkers. Random forest and support vector machine (SVM) models were trained on the selected and evaluated on the independent test set. RESULTS: Feature selection identified 21 overlapping biomarkers, including EPHB3, ATP5MJ, USP1, RANBP9, SLC11A2, S100P, PPP1R1A, ZIC1, NDRG2, SMARCA2, H2BC7, STK24, HBB, VPS45, H1, VEGFA, NFIB, ITGA6, RPRD1A, PRKD3, and ENSA, several of which have been implicated in TNBC progression and treatment resistance. In the test set, predictive performance was strong, with area under the curve (AUC) values of 91% for random forest and 89% for SVM. CONCLUSION: Transcriptomic profiling combined with machine learning provides a promising approach for predicting NAC response in TNBC. The identified biomarkers may inform precision treatment strategies and improve clinical outcomes in this high-risk patient population.
Effects of a sensorimotor-based, movement quality-focused intervention on functional mobility in breast cancer survivors: a multicenter randomized controlled trial.
Yang EJ, Kim HS, Jeon HR … +7 more , Suh MR, Ahn SY, Yoon JA, Lee SY, Won YH, Lee JY, Chung SH
Breast Cancer Res Treat · 2026 Mar · PMID 41874709 · Publisher ↗
PURPOSE: Breast cancer survivors frequently experience reductions in physical capacity and sensorimotor impairments following treatment. However, improvements in strength and endurance do not always translate into improv...
PURPOSE: Breast cancer survivors frequently experience reductions in physical capacity and sensorimotor impairments following treatment. However, improvements in strength and endurance do not always translate into improvements in functional mobility and balance-related outcomes. This study evaluated whether a sensorimotor-based rehabilitation program emphasizing movement control (Rehabilitation through Movement and Perception, ReMAP) could improve functional mobility and postural stability in breast cancer survivors. METHODS: In this multicenter randomized wait-list controlled trial, 71 breast cancer survivors (mean age 50.7 ± 8.9 years) with mild functional impairment who had completed curative breast cancer treatment at least 3 months prior to enrollment were assigned to a ReMAP intervention group (n = 41) or a wait-list control group (n = 30). The 8-week intervention consisted of supervised, low- to moderate-intensity sensorimotor exercises targeting postural alignment, coordination, and balance. Functional mobility was assessed using the Timed Up and Go (TUG) test. Secondary outcomes included handgrip strength and 6-min walk distance as indicators of physical capacity, disability assessed using the World Health Organization Disability Assessment Schedule (WHODAS 12), and postural stability quantified by kinematic measures of center-of-mass sway. RESULTS: Participants in the ReMAP group demonstrated a significantly greater improvement in functional mobility than controls, with a larger reduction in TUG time at 8 weeks (group × time interaction: β = - 0.97 s, 95% CI 1.93 to - 0.01; p = 0.049). Postural stability improved significantly, as evidenced by reductions in mediolateral and anteroposterior center-of-mass sway. No significant between-group differences were observed in handgrip strength, 6-min walk distance, or self-reported disability. Exploratory analyses suggested that improvements in TUG performance were more closely associated with changes in movement quality than with changes in physical capacity. CONCLUSIONS: A sensorimotor-based rehabilitation program improved functional mobility and postural stability in breast cancer survivors with relatively preserved physical capacity. Targeting movement quality may address key mechanisms underlying balance-related vulnerability in survivorship care.
Telehealth utilization during the COVID-19 pandemic: comparing breast cancer survivors to non-cancer patients and implications for current practice.
Hawkins LA, Rumano RP, Smith SS … +6 more , Beverly-Hery CM, Fisher JL, Clark A, Champion V, Oppong BA, Paskett ED
Breast Cancer Res Treat · 2026 Mar · PMID 41874692 · Full text
BACKGROUND: During the 2019 coronavirus (COVID-19) pandemic, in-person medical visits changed due to social distancing guidelines. Breast cancer (BC) patients, needing ongoing treatment or surveillance, faced increased c...
BACKGROUND: During the 2019 coronavirus (COVID-19) pandemic, in-person medical visits changed due to social distancing guidelines. Breast cancer (BC) patients, needing ongoing treatment or surveillance, faced increased challenges in accessing care. Telehealth became essential for providing convenient and cost-effective care while minimizing COVID-19 transmission. BC survivors, however, often value in-person visits for clinical exams. This study aimed to compare telehealth participation between patients with a history of BC and women without cancer history. METHODS: Adults aged 18 and older, including cancer patients, survivors, caregivers, and healthy volunteers, primarily from Ohio, were recruited with attention and inclusion of underserved and minority populations to complete a survey about COVID-19-related beliefs, practices, and knowledge. Recruitment involved (1) re-contacting participants from previous OSU studies (2) outreach via community partners and listservs to invite additional participants and caregivers. Sociodemographic characteristics by BC status were calculated using Chi square tests. Univariable and multivariable logistic regressions modeled association between the outcome of interest, telehealth participation, and BC status accounting for race, ethnicity, age, education, marital status, rurality, and insurance status. RESULTS: The final sample included 2265 participants, with 43.7% having a history of BC. Significant demographic differences were observed between participants with and without a history of breast cancer. Those with a previous BC diagnosis were younger on average (55.6 vs. 57.9 years, p < .001), had higher levels of educational attainment (p < .001), were less often married and more often divorced/widowed/separated (p = .037), and were more likely to have private insurance only and less likely to have both public and private coverage (p < .001). Telehealth use was lower during COVID-19 among BC survivors (41.5%) vs. those without cancer (63.9%) (p < 0.001). In a multivariable model, factors that were statistically significantly associated with increased utilization of telehealth were Black race (OR = 1.90, p-value 0.036), having some college education (OR = 1.50, p-value 0.034), being married (OR = 1.61, p-value 0.009), and being currently employed (OR = 1.25, p-value 0.050). BC diagnosis or survivor status was associated with decreased odds of telehealth use (OR: 0.72, p = 0.023). Among breast cancer patients with complete data (n = 645 of the 989 total), more than half used telehealth, with video visits being slightly more common than phone visits. Logistic regression analyses revealed increased telehealth use among patients with a history of BC was associated with age > 70, while decreased participation in telehealth was associated with higher educational status and having undergone surgical treatment. CONCLUSION: We found that Black race, having some college education, being married, and being employed were significantly associated with increased telehealth participation during the COVID-19 pandemic. Interestingly, BC diagnosis was associated with reduced odds of telehealth use. Subgroup analyses of patients with a history of BC showed decreased use of telehealth to be associated with higher education and recent surgery for BC. Further investigation is needed to understand the acceptability and barriers to telehealth among BC survivors, as this modality continues to play an expanding role in oncology care delivery in the post-pandemic era.
Automated calculation of background parenchymal enhancement as a biomarker of treatment responses and recurrence-free survival in breast cancer.
Zhu Y, Hadidchi R, Nguyen HQ … +8 more , Hariharan S, Weiss J, Hou W, Chung C, Luu HM, Ragupathi S, Maldjian T, Duong TQ
Breast Cancer Res Treat · 2026 Mar · PMID 41872564 · Full text
PURPOSE: To determine whether automated quantification of background parenchymal enhancement (BPE) from dynamic contrast-enhanced MRI (DCE-MRI) can serve as an imaging biomarker for clinical outcomes including overall su...
PURPOSE: To determine whether automated quantification of background parenchymal enhancement (BPE) from dynamic contrast-enhanced MRI (DCE-MRI) can serve as an imaging biomarker for clinical outcomes including overall survival (OS), recurrence-free survival (RFS), and pathological complete response (pCR) in breast cancer. METHODS: The multi-institutional data consisted of 922 biopsy-confirmed invasive breast cancer patients from the Duke-Breast-Cancer-MRI dataset and 152 patients with whole-breast pre- (T) and/or post (T) DCE-MRI from the I-SPY2 dataset for validation. Automated fibroglandular tissue (FGT) segmentation and BPE quantification were performed on DCE-MRI. The optimal intensity enhancement threshold by volume-based method was established against four radiologist-defined BPE categories. The area under the curve (AUC) was obtained for classification of BPE categories. Cox proportional hazards models were used to predict OS and RFS. Logistic regression was used to predict pCR. RESULTS: Peak-contrast BPE showed strong correlation with radiologist-defined BPE, achieving the best performance at a 55% signal enhancement threshold (AUC 0.70-0.86). The calculated BPE decreased after neoadjuvant chemotherapy. A reduction in calculated BPE grade after neoadjuvant chemotherapy was predictive of pCR for the high baseline BPE group (adjusted odds ratio = 5.88 [1.03, 33.33]) and for the low baseline BPE group (adjusted odds ratio = 6.54 [1.26, 33.94]). Baseline BPE was independently associated with improved OS (adjusted hazard ratio 0.58 [0.34, 0.99]) but not associated with RFS. CONCLUSION: Automated quantification of BPE from DCE-MRI provides an objective and reproducible imaging biomarker associated with treatment response and overall survival in breast cancer. These results support its potential utility for individualized risk stratification and therapeutic decision-making.
Rb expression in metastatic ER-positive breast cancer: implications for precision oncology.
Morrar D, Ross D, Razavi P … +4 more , Brogi E, Pareja F, Wen HY, Schwartz CJ
Breast Cancer Res Treat · 2026 Mar · PMID 41872428 · Publisher ↗
PURPOSE: The retinoblastoma protein (Rb) is a critical cell-cycle regulator, and its loss of function can lead to resistance to CDK4/6 inhibitors (CDK4/6i), which are the standard first-line treatment for estrogen recept...
PURPOSE: The retinoblastoma protein (Rb) is a critical cell-cycle regulator, and its loss of function can lead to resistance to CDK4/6 inhibitors (CDK4/6i), which are the standard first-line treatment for estrogen receptor (ER)-positive metastatic breast carcinoma (mBC). Thus, identifying Rb-deficient mBC is crucial for optimal personalized breast cancer management. This study aimed to determine the prevalence of Rb loss by immunohistochemistry (IHC) in a cohort of ER + mBC and to assess its correlation with RB1 genetic inactivation. METHODS: We analyzed Rb IHC in 50 consecutive ER-positive mBC. Histopathologic and clinical features were analyzed. p16 IHC was performed in a subset of Rb-deficient cases. Targeted next-generation tumor-normal sequencing (NGS) data using MSK-IMPACT were retrospectively analyzed in 38 mBCs. RESULTS: Rb loss was identified in 20% (10/50) of mBC, and was either partial (8%, 4/50) or complete (12%, 6/50). In all evaluable cases (100%, 9/9), Rb loss was associated with p16 positivity. Neuroendocrine (NE) features were observed in 40% (4/10) of mBCs with Rb loss. MSK-IMPACT data were available for six Rb-deficient cases and revealed pathogenic RB1 alterations in two (33%). None of the tumors with preserved Rb expression (80%, 40/50) showed RB1 genetic alterations or NE features. Notably, one mBC case demonstrated disease progression on CDK4/6 inhibitor therapy, accompanied by acquired Rb loss and acquisition of an NE phenotype. CONCLUSION: Rb loss in mBC can be reliably detected by Rb IHC, especially when interpreted alongside p16, offering a rapid and cost-effective means of assessing Rb status. This approach may identify Rb-deficient tumors that are missed by conventional methods, such as next-generation sequencing, and help guide personalized therapeutic strategies in patients with mBC.
Risk of CNS relapse following pathological complete response to neoadjuvant chemotherapy in early breast cancer.
de Moura Leite L, de Almeida GR, Tavares MC … +17 more , Cesca MG, Campos FAB, de Oliveira FA, Dornellas DMS, Saldanha EF, Guimarães PT, de Arruda DDS, de Held MFSD, Viana RL, Moura FGR, Loose SK, Silva SF, Pirolli R, Fogassa CAZ, Mattos BRS, Sanches SM, de Lima VCC
Breast Cancer Res Treat · 2026 Mar · PMID 41866643 · Full text
PURPOSE: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) improves outcomes in breast cancer (BC); however it may not prevent brain metastases. We evaluated central nervous system (CNS) recurrenc...
PURPOSE: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) improves outcomes in breast cancer (BC); however it may not prevent brain metastases. We evaluated central nervous system (CNS) recurrence patterns in early-stage BC following NAC according to pCR. METHODS: All consecutive stage I-III BC treated with NAC and surgery at a single center between 2007 and 2018 were analyzed. Endpoints included the impact of pCR on CNS recurrence across BC subtypes-hormone receptor-positive(HR)/HER2-negative, HER2-positive and triple-negative (TNBC), CNS recurrence patterns and overall survival (OS) after CNS relapse. Statistical comparisons included Fisher's Exact test, Chi-square, Kaplan-Meier, and regression analyses. RESULTS: Among 1147 patients, 537 had HR-positive/HER2-negative, 301 HER2-positive, 309 TNBC, mostly stage III, treated with anthracycline + taxane NAC, and trastuzumab if HER2-positive. Three hundred sixty-five achieved pCR (59/537 HR-positive/HER2-negative, 158/301 HER2-positive, 148/309 TNBC). CNS recurrence occurred in 72 (6.2%) patients, with no difference between pCR and non-pCR (4.7 vs. 7.0%, p = 0.15). Across subtypes, there was no difference for HR-positive/HER2-negative (3.4 vs. 4%, p = 1.0), TNBC (5.4 vs. 9.3%, p = 0.2), however there was a reduction in HER2-positive (4.4 vs. 14.7%, p = 0.003) after pCR. Isolated CNS relapse was the predominant pattern of CNS metastasis (82.4%) in pCR, particularly in HER2-positive. Median OS after CNS relapse was 12 months. Multivariate analysis identified HER2-positive, TNBC, and cN2-3 status as independent predictors of CNS recurrence. CONCLUSION: Although pCR was not associated with a lower overall risk of CNS recurrence, it predicted a reduced risk in HER2-positive disease. Isolated CNS relapse predominated, suggesting a sanctuary effect.
House value as an individual socioeconomic indicator for breast cancer survival and late-stage diagnosis: a population-based cohort study from Northern Ireland.
Baxter SM, McShane CM, McIntosh SA … +10 more , Bennett D, Sharma M, Lohfeld L, Middleton DRS, Savage G, Fitzpatrick D, McBrien A, McCallion D, Gavin A, Cardwell CR
Breast Cancer Res Treat · 2026 Mar · PMID 41863581 · Full text
PURPOSE: Socioeconomic inequalities in breast cancer survival persist in the UK. Area-based deprivation measures may underestimate socioeconomic effects by assigning average deprivation levels to all area inhabitants. Th...
PURPOSE: Socioeconomic inequalities in breast cancer survival persist in the UK. Area-based deprivation measures may underestimate socioeconomic effects by assigning average deprivation levels to all area inhabitants. This study investigated associations between house value (individual-level) and area-based deprivation with breast cancer outcomes in Northern Ireland. METHODS: Women diagnosed with breast cancer from 2011 to 2021 were identified using the Northern Ireland Cancer Registry. House value was determined from Valuation and Lands Agency property valuation data, and area-based deprivation from the Northern Ireland Multiple Deprivation Measure. The primary outcome was breast cancer-specific mortality. Secondary outcomes were stage at diagnosis and all-cause mortality. Cox regression models calculated adjusted hazard ratios (HR) and 95% confidence intervals (95% CIs) for mortality by house value category and deprivation, adjusting for confounders. RESULTS: Among 12,766 women with breast cancer, women in the lowest versus highest house value category had a 60% increase in mortality (adjusted HR = 1.60 95% CI 1.34, 1.92; per 20 percentile decrease adjusted HR = 1.12 95% CI 1.08, 1.16) and were more likely diagnosed with stage 4 disease (7.5% versus 4.1%; P < 0.001). Women living in the most versus least deprived areas had a 26% increase in mortality (adjusted HR = 1.26 95% CI 1.08, 1.47; per 20 percentile decrease adjusted HR = 1.05 95% CI 1.01, 1.08) but had no difference in stage 4 disease (5.9% vs. 5.0%; P = 0.157). CONCLUSION: Individual-level house value demonstrated stronger associations with breast cancer outcomes than area-level deprivation, suggesting it may serve as a more sensitive indicator for monitoring health inequalities in cancer.
Correction to: A Canadian real‑world, multi‑center, prospective, observational study assessing the treatment duration, the treatment sequence, and the overall survival for patients treated with endocrine therapy ± targeted therapy in HR + HER2‑negative advanced breast cancer.
Doyle C, Lohmann AE, Iqbal N … +13 more , Henning JW, Kulkarni S, Califaretti N, Hilton J, Ferrario C, Bouganim N, Mates M, Guillemette S, Leite R, Caron MA, Thireau F, Machado A, Chia S
Breast Cancer Res Treat · 2026 Mar · PMID 41854885 · Full text
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Long-term outcomes of eribulin‑based neoadjuvant chemotherapy for triple‑negative breast cancer patients stratified by homologous recombination deficiency status: results of the randomized JBCRG-22 study.
Masuda N, Yasojima H, Bando H … +15 more , Yamanaka T, Shigematsu H, Takahashi M, Nagai SE, Ito M, Aruga T, Tokiwa M, Imoto S, Nakamura R, Ishiguro H, Kawabata H, Saji S, Haga H, Morita S, Toi M
Breast Cancer Res Treat · 2026 Mar · PMID 41854792 · Full text
PURPOSE: To investigate long-term outcomes for triple‑negative breast cancer (TNBC) patients enrolled in JBCRG-22. METHODS: TNBC (cT1c-T3, cN0-1, M0) patients were stratified by homologous recombination deficiency (HRD)...
PURPOSE: To investigate long-term outcomes for triple‑negative breast cancer (TNBC) patients enrolled in JBCRG-22. METHODS: TNBC (cT1c-T3, cN0-1, M0) patients were stratified by homologous recombination deficiency (HRD) and germline BRCA mutation (gBRCAm) status. Group A patients (aged < 65 years with HRD-positive tumors, or those with gBRCAm, if available) were randomized to receive 4 cycles of weekly paclitaxel (group A1) or eribulin (group A2), both with carboplatin, followed by 4 cycles of anthracycline. Group B patients (aged < 65 years with HRD-negative tumors or aged ≥ 65 years) were randomized to receive 6 cycles of eribulin plus cyclophosphamide (group B1) or eribulin plus capecitabine (group B2). Five-year invasive disease-free survival (IDFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed. Additionally, data were analyzed by biomarker levels including lymphocyte count (LC) and neutrophil-to-lymphocyte ratio (NLR). RESULTS: Ninety-nine patients were followed for a median of 5.6 years. In patients who received eribulin-based therapy (groups A2 + B1 + B2), 5-year IDFS and OS rates, respectively, were 95% and 100% in patients who achieved pCR after neoadjuvant therapy (n = 20) and 71.4% and 80.2% in those who did not (n = 56), showing significantly better prognosis in the pCR cohort (p < 0.05). OS tended to be better in patients with baseline LC ≥ 1500/mm and NLR < 3, particularly in eribulin-treated patients, although differences were non-significant. CONCLUSIONS: These findings will help guide the development of eribulin-based neoadjuvant chemotherapy for selected TNBC patients. Our exploratory analysis of LC and NLR results may help inform clinical prediction models for eribulin-treated patients. TRIAL REGISTRATION: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( https://www.umin.ac.jp/ctr/index-j.htm ) with unique trial number UMIN000023162. The Japan Breast Cancer Research Group trial number is JBCRG-22.
Treatment patterns and safety of adjuvant therapy after chemoimmunotherapy for early-stage triple-negative breast cancer: real-world data from the Neo-Real/GBECAM 0123 study.
Andrade MO, Bonadio RC, Ipiña A … +31 more , Testa L, Tavares MC, Balint FC, Dos Anjos CH, Gagliato DM, de Brito ML, Winocur M, Assad-Suzuki D, Rosa DD, Gomes NJB, Nunes NCC, de Sousa IM, Gouveia MC, Madasi F, Bines J, Gallina C, Ferreira RDP, Santos CL, Tavares M, Monteiro MR, de Souza ZS, Gomes AMU, Zucchetti BM, Ferrari A, Monteiro MMF, Signorini PA, Sanches S, Hoff PM, Ferreira G, Estevez-Diz MDP, Barroso-Sousa R
Breast Cancer Res Treat · 2026 Mar · PMID 41848921 · Publisher ↗
PURPOSE: For early-stage triple-negative breast cancer (TNBC), the KEYNOTE-522 trial established neoadjuvant pembrolizumab plus chemotherapy (CT), followed by adjuvant pembrolizumab, as the standard of care. Nevertheless...
PURPOSE: For early-stage triple-negative breast cancer (TNBC), the KEYNOTE-522 trial established neoadjuvant pembrolizumab plus chemotherapy (CT), followed by adjuvant pembrolizumab, as the standard of care. Nevertheless, uncertainties remain on how to integrate this regimen with other adjuvant therapies such as capecitabine or olaparib. This study evaluated real-world treatment patterns and safety of adjuvant therapies following neoadjuvant chemoimmunotherapy. METHODS: The Neo-Real study includes patients with TNBC treated with neoadjuvant pembrolizumab plus CT in Brazil and Argentina. This study describes real-world adjuvant treatment patterns and safety; survival outcomes are not reported in this analysis. RESULTS: Among 726 patients included, 692 underwent surgery, and 62.9% achieved pathologic complete response (pCR). Of those with pCR, 84.8% received adjuvant pembrolizumab alone, while 14.3% received no adjuvant therapy. Among patients with residual disease and no germline BRCA1/2 mutations (n = 207), 57.5% received pembrolizumab plus capecitabine, 26.1% pembrolizumab alone, and 12.6% capecitabine alone. In BRCA1/2-mutated patients (n = 26), 57.7% received pembrolizumab plus olaparib, 19.2% pembrolizumab alone, and 11.5% olaparib alone. Safety data were available for 359 patients. Adjuvant pembrolizumab alone caused a lower incidence of grade ≥ 3 AEs (6.7%) compared with combination regimens (P = 0.002). Drug discontinuation due to toxicity occurred in 5.7%, 11.2%, and 7.7% of patients receiving pembrolizumab, pembrolizumab + capecitabine, and pembrolizumab + olaparib, respectively (P = 0.126). CONCLUSION: Most patients with pCR continued adjuvant pembrolizumab, while combination strategies predominated among those with residual disease and were associated with higher rates of grade ≥ 3 AEs. The efficacy of these combined regimens remains to be determined.
Omission of axillary surgery in early breast cancer with negative lymph nodes: a systematic review and meta-analysis of randomized clinical trials.
Castelo BB, Brito LGO, Torresan RZ … +2 more , Filho CC, Duarte GM
Breast Cancer Res Treat · 2026 Mar · PMID 41848913 · Full text
PURPOSE: To evaluate whether the omission of axillary surgery impacts clinical outcomes in patients with early-stage breast cancer and clinically negative lymph nodes. METHODS: We conducted a systematic review and meta-a...
PURPOSE: To evaluate whether the omission of axillary surgery impacts clinical outcomes in patients with early-stage breast cancer and clinically negative lymph nodes. METHODS: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing no axillary surgery with standard axillary interventions (sentinel lymph node biopsy [SLNB] or axillary dissection [AD]). This study followed PRISMA guidelines and was registered in PROSPERO (CRD420250653779). Searches were conducted in PubMed, Web of Science, and Embase through June 2025. Outcomes assessed included overall survival (OS), disease-free survival (DFS), and axillary recurrence (AR). Meta-analyses were performed using RevMan 5.4. Risk of bias was assessed using the RoB 2 tool. RESULTS: Out of 853 records, seven RCTs including 8806 patients met the inclusion criteria. Among them, 2,915 patients underwent no axillary surgery, while 5891 received surgical axillary treatment. Two trials compared no surgery with SLNB, and five compared no surgery with AD. No significant differences were found in OS (OR = 1.02; 95% CI, 0.86-1.20; p = 0.84; I = 36%) or DFS (OR = 0.80; 95% CI, 0.63-1.00; p = 0.05; I = 63%). AR was significantly lower in the axillary surgery group (OR = 0.18; 95% CI, 0.10-0.31; p < 0.01; I = 39%). CONCLUSION: The omission of axillary surgery in early-stage breast cancer with clinically negative lymph nodes does not negatively impact overall or disease-free survival. However, it is associated with a higher-though still low-risk of axillary recurrence.
ESR1 polymorphisms were associated with aromatase inhibitors induced musculoskeletal symptoms in breast cancer patients.
Jing F, Jiang L, Cao Y … +4 more , Tian M, Qiu J, Tang L, Hu Y
Breast Cancer Res Treat · 2026 Mar · PMID 41848880 · Publisher ↗
PURPOSE: Aromatase Inhibitors Associated Musculoskeletal Symptoms (AIMSS) are common side effects among hormone receptor-positive breast cancer patients, significantly affecting patients' treatment adherence and quality...
PURPOSE: Aromatase Inhibitors Associated Musculoskeletal Symptoms (AIMSS) are common side effects among hormone receptor-positive breast cancer patients, significantly affecting patients' treatment adherence and quality of life. The individual genetic susceptibility mechanism underlying AIMSS was not well understood yet. This study aimed to validate the association between genetic polymorphisms and AIMSS among Chinese breast cancer patients. METHODS: This was a cross-sectional study. Participants were recruited from a tertiary hospital in China from May 2023 to June 2024. Musculoskeletal symptoms were measured using the Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands (M-SACRAH) and the Western Ontario and McMaster Osteoarthritis Index (WOMAC) among hormone receptor-positive patients receiving aromatase inhibitor therapy. Six genes (i.e., ESR1, ESR2, RANK, OPG, TCL1A and CYP19A1) related 20 SNPs were tested. Multivariate linear regression analysis was used to explore the association between different genotypes and the severity of AIMSS. RESULTS: Among 171 participants, the standardized M-SACRAH score was 3.33 (IQR 0.00-9.17) and the standardized WOMAC score was 5.83 (IQR 2.08-17.29). Patients carrying the ESR1 rs9340799 AG genotype (vs. AA) had a significant reduction in the severity of hand joint symptoms [adjusted β = -4.51, 95% CI: -8.29, -0.73, p = 0.020] and knee/hip joint symptoms [adjusted β = -4.44, 95% CI: -8.49, -0.39, p = 0.032]. The ESR1 rs2077647 TC genotype (vs. TT) was related to lower level of hand joint symptoms [adjusted β = -5.03, 95% CI: -8.69, -1.37, p = 0.007] and knee/hip joint symptoms [adjusted β = -5.04, 95% CI: -8.97, -1.12, p = 0.012]. The ESR1 rs2234693 TC genotype (vs. TT) [adjusted β = -4.06, 95% CI: -8.09, -0.03, p = 0.049] was associated with lower level of knee/hip joint symptoms. No significant associations emerged between ESR2, RANKL, OPG, TCL1A, or CYP19A1 variants and AIMSS. CONCLUSIONS: This study preliminarily validated the association between ESR1 polymorphisms (rs9340799, rs2077647, and rs2234693) and aromatase inhibitor associated musculoskeletal symptoms in hormone receptor-positive breast cancer among Chinese patients. Future research should focus on dissecting their molecular mechanisms, and integrating genetic data with clinical interventions to optimize the management strategies of musculoskeletal toxicity.
Comment on: "Prognostic performance of thymidine kinase 1 activity in patients with hormone receptor-positive and HER2-negative metastatic breast cancer treated with CDK4/6 and aromatase inhibitors".
Manikya S, Vadhithala V, Kumar R … +1 more , Nainwal P
Breast Cancer Res Treat · 2026 Mar · PMID 41848791 · Publisher ↗
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Unlocking the predictive value of post-neoadjuvant immune biomarkers in breast cancer: neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII).
Guirao García ME, Marín Rodríguez P, Servet Pérez de Lema CM … +11 more , Blaya Boluda N, Sánchez Henarejos P, Moya Hernández MÁ, Gottlob Pérez A, Marín Hernández C, de la Morena Barrio P, García Garre E, García-Martínez E, Ayala de la Peña F, Piñero Madrona A, García-Torralba E
Breast Cancer Res Treat · 2026 Mar · PMID 41838228 · Full text
PURPOSE: To evaluate the potential prognostic value of two peripheral immune biomarkers-neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII)-in breast cancer patients treated with neoadjuvant...
PURPOSE: To evaluate the potential prognostic value of two peripheral immune biomarkers-neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII)-in breast cancer patients treated with neoadjuvant chemotherapy, and to assess their association with pathological complete response (pCR) and other predictive factors. In addition, to determine whether prognostic or predictive differences exist between baseline and post-neoadjuvant values of these biomarkers. METHODS: We analyzed 801 women with early breast cancer treated with neoadjuvant chemotherapy, evaluating clinical and pathological data, survival outcomes, NLR (continuous and categorical) and SII. RESULTS: Baseline NLR was significantly higher in younger patients, in those with positive pathological nodes, and in the HER2 + /HR - subtype, while baseline SII was elevated in the triple-negative subtype. Post-neoadjuvant chemotherapy (post-NCT) NLR and SII showed only weak associations with estrogen receptor expression, yet both were independently associated with pCR (post-NCT NLR: OR = 0.91; 95% CI: 0.84-0.98; p = 0.02; post-NCT SII: OR = 0.65; 95% CI: 0.47-0.89; p = 0.008). Neither biomarker showed a significant impact on overall or progression-free survival. CONCLUSION: Post-treatment NLR and SII may reflect chemotherapy-induced immune changes and are associated with pathological complete response, but their additional predictive value is uncertain, and no prognostic impact was observed.
Molecular imaging of tucatinib-induced cellular and TME changes in preclinical models of HER2 + breast cancer.
Song PN, Mansur A, Gallegos CA … +3 more , Ghanate P, Lapi SE, Sorace AG
Breast Cancer Res Treat · 2026 Mar · PMID 41824101 · Full text
INTRODUCTION: Tucatinib, a small molecule HER2 inhibitor, was approved in inoperable or metastatic HER2 + breast cancer. As many patients have tumors in challenging surgical locations, there is a need for imaging metrics...
INTRODUCTION: Tucatinib, a small molecule HER2 inhibitor, was approved in inoperable or metastatic HER2 + breast cancer. As many patients have tumors in challenging surgical locations, there is a need for imaging metrics to characterize tucatinib response and microenvironment impact. Molecular imaging can be used to quantify dynamic molecular changes that precede tumor size alterations and can target proliferation (fluorothymidine, [F]-FLT), hypoxia (fluoromisonidazole, [F]-FMISO) and HER2 expression ([Zr]-Pertuzumab) with positron emission tomography (PET) imaging. The goal of this study is to non-invasively characterize tucatinib response in HER2 + breast cancer and quantify microenvironment modulation with advanced PET imaging. METHODS: Mice with HER2 + human cell line (BT474) or patient derived xenograft (BCM 3472) tumors were treated with 50 mg/kg tucatinib and enrolled into imaging cohorts: imaged with [F]-FLT-PET on days 0, 3 and 7, [F]-FMISO-PET on days 0, 3 and 7, or [Zr]Zr-Pertuzumab-PET on days 0 and 14. Proliferation, hypoxia and HER2 expression were quantified with standardized uptake value. A Mann-Whitney U Test assessed significance between groups. RESULTS: Tucatinib-treated human cell line and PDX tumors had significantly decreased hypoxia and proliferation relative to control tumors (p < 0.05). Tucatinib-treated BT474 tumors had significantly decreased HER2 expression (p < 0.05); however, no significant HER2 change was observed in BCM3472 tumors. CONCLUSION: Tucatinib significantly decreases intratumoral proliferation and hypoxia in both cell-line and patient-derived xenograft models of HER2 + breast cancer, which can be longitudinally quantified with PET imaging. Our data suggests molecular imaging may improve understanding and prediction of tucatinib response.
Comparative effectiveness of CDK4/6 inhibitors in metastatic breast cancer: using the target trial emulation framework to investigate overall survival in routine care.
Brufsky AM, Finn RS, Metzger O … +7 more , Goncalves R, Huang-Bartlett C, Sreenivasan S, Nur U, Davies J, Grigorenko A, Long GH
Breast Cancer Res Treat · 2026 Mar · PMID 41793559 · Full text
PURPOSE: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus aromatase inhibitor (AI) is the recommended first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic br...
PURPOSE: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus aromatase inhibitor (AI) is the recommended first-line treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (mBC). CDK4/6i head-to-head trials have not been conducted, and randomized controlled trials (RCTs) report inconsistent overall survival (OS) results despite similar effects on the primary endpoint of progression-free survival. Real-world evidence can complement RCTs but selection biases and confounders can challenge interpretation. Target trial emulation applies the principles of RCTs to observational data to overcome such challenges. We emulated a hypothetical target trial to investigate whether causal differences in OS between patients receiving first-line CDK4/6i plus AI exist in the real-world clinical setting. METHODS: We used de-identified data (Flatiron Health mBC Enhanced Data Mart) from patients ≥ 18 years old at primary diagnosis who were treated with first-line palbociclib/ribociclib/abemaciclib plus AI for mBC between 2018 and 2024. Statistical adjustments included stabilized inverse-probability weighting (sIPTW), investigation of missing data mechanisms, and analyses for unmeasured confounders. RESULTS: 2626 patients were included (palbociclib n = 1686; ribociclib n = 537; abemaciclib n = 403). After sIPTW, baseline characteristics were balanced between groups and there was no observable difference in real-world OS (ribociclib vs palbociclib, adjusted hazard ratio 1.00, 95% CI: 0.81-1.24; abemaciclib v palbociclib: 0.91, 95% CI: 0.74-1.14). Results were consistent after sensitivity analyses. CONCLUSION: Using target trial emulation, real-world OS is similar with palbociclib/ribociclib/abemaciclib plus AI. These findings may contribute to the development of combination strategies to improve clinical outcomes and to guide clinical decision-making.
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