Breast Cancer Research and Treatment最新文献

{"title":"Sacituzumab-induced severe or febrile neutropenia and G-CSF utilization and cost for advanced HER2-negative breast cancer: a single-center retrospective analysis.","authors":"Grace Tam, Donald Waddell, Jincong Q Freeman, Nan Chen, Heng Yang","doi":"10.1007/s10549-026-07971-z","DOIUrl":"10.1007/s10549-026-07971-z","url":null,"abstract":"<p><strong>Purpose: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Provider level facilitators and barriers towards neoadjuvant chemotherapy for triple negative and HER2 + breast cancer: a survey of Ontario surgeons.","authors":"Gary Ko, Elwyn Zhang, Elliott Yee, Julie Hallet, Natalie Coburn, Frances C Wright, Sonal Gandhi, Katarzyna J Jerzak, Andrea Eisen, Nicole J Look Hong, Amanda Roberts","doi":"10.1007/s10549-026-07969-7","DOIUrl":"https://doi.org/10.1007/s10549-026-07969-7","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between the drainage time in dynamic indocyanine green lymphography (ICG) and axillary lymph nodes metastatic involvement in breast cancer patients-a prospective study.","authors":"Anuszkiewicz Karolina, Ekman Marcin, Graczyk Magdalena, Drozd Mateusz, Drucis Kamil, Jankau Jerzy","doi":"10.1007/s10549-026-07968-8","DOIUrl":"https://doi.org/10.1007/s10549-026-07968-8","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with and patterns of alcohol intake in late survivorship for breast cancer survivors.","authors":"Sanjna Rajput, Robert A Vierkant, Kayleigh N Olson, Nicole L Larson, Daniela L Stan, Dawn M Mussallem, Stacy D D'Andre, Fergus J Couch, Janet E Olson, Ciara C O'Sullivan, Kathryn J Ruddy","doi":"10.1007/s10549-026-07957-x","DOIUrl":"10.1007/s10549-026-07957-x","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate alcohol intake trends and identify demographic, clinical, lifestyle, and socioeconomic factors associated with alcohol consumption in late survivorship among breast cancer survivors.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing and Mendelian randomization identify context-dependent LIPA-associated classical monocyte states in sepsis and breast cancer.","authors":"Wenjing Wang, Mengting Liu, Xiang Li","doi":"10.1007/s10549-026-07965-x","DOIUrl":"https://doi.org/10.1007/s10549-026-07965-x","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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.","authors":"Kelsey E Maslana, Ryan D Burns, Yang Bai, Mary C Playdon, Paul A Estabrooks, Carson Saviers-Steiger, Emily R Dunston, Patrick Galyean, Elisabeth R Kimball, Susan L Zickmund, Pamela A Hansen, Cornelia M Ulrich, Paul C LaStayo, David Steinberg, Christopher S Noren, A 'Lisha Finch, Leanne Seckinger, Sonal Oza, Kirstyn E Brownson, Adriana M Coletta","doi":"10.1007/s10549-026-07973-x","DOIUrl":"https://doi.org/10.1007/s10549-026-07973-x","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>CORE program participation was not associated with reduced SB. Strategies to reduce SB should be incorporated within programs aimed at increasing physical activity engagement.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"External validation of PREDICT Breast v3.1 for overall survival in international cohorts, including young and invasive lobular subgroups.","authors":"Elfi M Verheul, Frank Doornkamp, Iurii Petrov, Sabine Siesling, Hester F Lingsma, Linetta B Koppert, Lara W A Vreven, Adri C Voogd, Maria Margarete Karsten, Lea Doppelbauer, Pimrapat Gebert, Narsis Kiani, Simona Borstnar, Paul D P Pharoah, Elham Hedayati, Ewout W Steyerberg, David van Klaveren","doi":"10.1007/s10549-026-07958-w","DOIUrl":"10.1007/s10549-026-07958-w","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Black and White disparity in U.S. female breast cancer mortality: a nationwide analysis, 1999-2023.","authors":"Hang Yi, Yifei Zhong, Daiwen Xing, Yan Wang, Shiman Xie, Yinyan Gao, Feng Mao, Xuefei Wang","doi":"10.1007/s10549-026-07959-9","DOIUrl":"https://doi.org/10.1007/s10549-026-07959-9","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topoisomerase I inhibitor antibody-drug conjugates in breast cancer: the relevance of the DNA damage response to resistance, response, and combination treatment strategies.","authors":"Dayle K Wang, Julia A Steele, Susan R Opalenik, Justin M Balko","doi":"10.1007/s10549-026-07964-y","DOIUrl":"https://doi.org/10.1007/s10549-026-07964-y","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant twelve weekly paclitaxel-carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer.","authors":"Yasmin Leshem, Inbal Golomb, Asia Zubkov, Yael Bar, Shlomit Strulov Shachar, Shir Lerner, Noa Keren-Khadmy, Amir Sonnenblick","doi":"10.1007/s10549-026-07942-4","DOIUrl":"10.1007/s10549-026-07942-4","url":null,"abstract":"<p><strong>Purpose: </strong>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).</p><p><strong>Methods: </strong>We conducted a retrospective analysis of patients with HER2-positive breast cancer treated with neoadjuvant 12wTCHP in a single tertiary medical center.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13068743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}