NPJ Breast CancerPub Date : 2025-05-10DOI: 10.1038/s41523-025-00760-9
Beatrice Taurelli Salimbeni, Fabiola Giudici, Carlo Pescia, Pier Paolo Maria Berton Giachetti, Roberta Scafetta, Paola Zagami, Antonio Marra, Dario Trapani, Angela Esposito, Simone Scagnoli, Bruna Cerbelli, Andrea Botticelli, Elisabetta Munzone, Nicola Fusco, Carmen Criscitiello, Giuseppe Curigliano
{"title":"Prognostic impact of tumor-infiltrating lymphocytes in HER2+ metastatic breast cancer receiving first-line treatment.","authors":"Beatrice Taurelli Salimbeni, Fabiola Giudici, Carlo Pescia, Pier Paolo Maria Berton Giachetti, Roberta Scafetta, Paola Zagami, Antonio Marra, Dario Trapani, Angela Esposito, Simone Scagnoli, Bruna Cerbelli, Andrea Botticelli, Elisabetta Munzone, Nicola Fusco, Carmen Criscitiello, Giuseppe Curigliano","doi":"10.1038/s41523-025-00760-9","DOIUrl":"https://doi.org/10.1038/s41523-025-00760-9","url":null,"abstract":"<p><p>Breast cancer (BC) is a leading cause of death among women, with approximately 30% HER2-positive (HER2+). Although HER2-targeted therapies have improved outcomes for patients with HER2+ metastatic breast cancer (mBC), clinical challenges and prognostic variability remain. Tumor-infiltrating lymphocytes (TILs) have emerged as prognostic and predictive biomarkers in various tumors, including BC, but their role in HER2+ mBC is poorly understood. This multicentric retrospective cohort study evaluated the prognostic significance of TILs in 110 patients with HER2+ mBC treated with pertuzumab, trastuzumab, and taxane-based chemotherapy at two Italian institutes from June 2013 to May 2024. TILs were assessed on metastatic or primary tumor samples. High TILs levels (>5%) were independently associated with longer PFS and OS. TILs levels were higher in primary tumours than in metastases (p = 0.009), with significant variation by metastatic site. These findings underscore the potential of TILs as prognostic biomarkers in HER2+ mBC, necessitating further prospective studies.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"41"},"PeriodicalIF":6.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ Breast CancerPub Date : 2025-05-07DOI: 10.1038/s41523-025-00755-6
Rachel Jaber Chehayeb, Nicole Odzer, Roberta A Albany, Leah Ferrucci, Daniel Sarpong, Rafael Perez-Escamilla, Jessica B Lewis, Amanda I Phipps, Allison Meisner, Lajos Pusztai
{"title":"Breastfeeding attributable fraction of triple negative breast cancer in the US.","authors":"Rachel Jaber Chehayeb, Nicole Odzer, Roberta A Albany, Leah Ferrucci, Daniel Sarpong, Rafael Perez-Escamilla, Jessica B Lewis, Amanda I Phipps, Allison Meisner, Lajos Pusztai","doi":"10.1038/s41523-025-00755-6","DOIUrl":"https://doi.org/10.1038/s41523-025-00755-6","url":null,"abstract":"<p><p>Rates of triple negative breast cancer (TNBC) are higher in Black women than in non-Hispanic White women. Breastfeeding duration and younger age at first birth are known risk factors for TNBC and vary by race. To quantify the contribution of these risk factors to disparities in TNBC, we calculated the population-attributable fraction (PAF). A PubMed search was performed to identify relevant studies and pooled odds ratios for breastfeeding for < 6 months and age at first birth < 25 years were calculated. PAF was calculated using the Levin formula. PAF of breastfeeding for < 6 months was 12% (95% confidence interval (CI) 5-20%) among White women and 15% (95%CI 3-26%) among Black women. We estimate that up to 15% of annual new TNBC in Black women and 12% in White women might be avoided by supporting breastfeeding. Policies supporting breastfeeding could hence reduce TNBC incidence and lessen racial disparities.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"40"},"PeriodicalIF":6.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"MUC1-C dependency in drug resistant HR+/HER2- breast cancer identifies a new target for antibody-drug conjugate treatment.","authors":"Ayako Nakashoji, Atrayee Bhattacharya, Hiroki Ozawa, Naoki Haratake, Keisuke Shigeta, Atsushi Fushimi, Nami Yamashita, Akira Matsui, Shoko Kure, Tomoe Kameyama, Makoto Takeuchi, Kazumasa Fukuda, Takamichi Yokoe, Aiko Nagayama, Tetsu Hayahsida, Yuko Kitagawa, Renyan Liu, Antonio Giordano, Rinath Jeselsohn, Geoffrey I Shapiro, Donald Kufe","doi":"10.1038/s41523-025-00751-w","DOIUrl":"10.1038/s41523-025-00751-w","url":null,"abstract":"<p><p>Treatment of hormone receptor (HR)-positive, HER2-negative breast cancer (HR+/HER2- BC) is limited by resistance to endocrine therapy (ET) and CDK4/6 inhibitors. There is no known common pathway that confers resistance to these agents. We report that (i) the MUC1 gene is upregulated in HR+/HER2- BCs and (ii) the MUC1-C protein regulates estrogen receptor alpha (ER)-driven transcriptomes. Mechanistically, we demonstrate that MUC1-C is necessary for expression of SRC-3 and MED1 coactivators that drive ER-mediated target gene transcription. Cells with ESR1 mutations that confer ET resistance, as well as cells with acquired resistance to the CDK4/6 inhibitor abemaciclib, are dependent on MUC1-C for (i) expression of these coactivators and ER target genes, (ii) survival, and (iii) self-renewal capacity. In support of these results, we show that treatment of HR+/HER2- BC cells with an anti-MUC1-C antibody-drug conjugate (ADC) effectively inhibits survival, self-renewal and tumorgenicity. These findings indicate that MUC1-C is a common effector of drug-resistant HR+/HER2- BC cells and is a potential target for their treatment.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"39"},"PeriodicalIF":7.6,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ Breast CancerPub Date : 2025-04-25DOI: 10.1038/s41523-025-00753-8
Rodrigo Sánchez-Bayona, Olga Martínez-Sáez, Denys Romero-Romero, Elia Seguí, Esther Carcelero, Pablo Tolosa, Jesús Soberino, Manuel Alva, Tomás Pascual, Laura Lema, Isabel Garcia-Fructuoso, Maria Angeles Cobos-Fernandez, Maria Rey, Luis Manso, Angela Aguirre, Ainhoa Madariaga, Valeria Sirenko, Cristina González-Deza, Paula Blasco, Astrid Mayhua, Oleguer Castillo, Patricia Galván, Esther Sanfeliu, Guillermo Villacampa, Wesley Buckingham, Mercedes Marín-Aguilera, Laia Paré, Patricia Villagrasa, Charles M Perou, Julia Maues, Fara Brasó-Maristany, Eva Ciruelos, Aleix Prat
{"title":"HER2DX ERBB2 mRNA score in first-line advanced HER2-positive breast cancer treated with chemotherapy, trastuzumab, and pertuzumab.","authors":"Rodrigo Sánchez-Bayona, Olga Martínez-Sáez, Denys Romero-Romero, Elia Seguí, Esther Carcelero, Pablo Tolosa, Jesús Soberino, Manuel Alva, Tomás Pascual, Laura Lema, Isabel Garcia-Fructuoso, Maria Angeles Cobos-Fernandez, Maria Rey, Luis Manso, Angela Aguirre, Ainhoa Madariaga, Valeria Sirenko, Cristina González-Deza, Paula Blasco, Astrid Mayhua, Oleguer Castillo, Patricia Galván, Esther Sanfeliu, Guillermo Villacampa, Wesley Buckingham, Mercedes Marín-Aguilera, Laia Paré, Patricia Villagrasa, Charles M Perou, Julia Maues, Fara Brasó-Maristany, Eva Ciruelos, Aleix Prat","doi":"10.1038/s41523-025-00753-8","DOIUrl":"https://doi.org/10.1038/s41523-025-00753-8","url":null,"abstract":"<p><p>In advanced HER2-positive breast cancer, the standard taxane-trastuzumab-pertuzumab (THP) regimen faces competition from new therapies, emphasizing the need for biomarkers to guide treatment. This study evaluates the HER2DX ERBB2 mRNA score as a prognostic predictor, aiming to tailor treatment strategies. We retrospectively analyzed 94 patients treated with the THP regimen between 2010 and 2024. The HER2DX ERBB2 mRNA score was categorized as low (n = 14), medium (n = 20), or high (n = 60), and its correlation with progression-free survival (PFS) and overall survival (OS) was assessed using Cox regression models. The median follow-up was 31.5 months. Patients with ERBB2-high scores had significantly better median PFS (33.9 vs. 10.6 months, hazard ratio [HR] = 0.40, 95% CI: 0.24-0.69, p < 0.001) and OS (not reached vs. 30.8 months, HR = 0.26, 95% CI: 0.13-0.49, p < 0.001) compared to ERBB2-low patients. Based on these findings, further validation of this biomarker in tumor samples from the CLEOPATRA phase III trial is ongoing, which could help optimize treatment strategies in this population.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"37"},"PeriodicalIF":6.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Body composition metrics as a determinant of trastuzumab deruxtecan related toxicity and response.","authors":"Shiran Yaacobi Peretz, Rivka Kessner, Yael Bar, Amir Sonnenblick, Shir Lerner, Ariella Deutsch-Lukatsky, Karteek Popuri, Mirza Faisal Beg, Shlomit Strulov Shachar","doi":"10.1038/s41523-025-00754-7","DOIUrl":"https://doi.org/10.1038/s41523-025-00754-7","url":null,"abstract":"<p><p>Body composition is an important predictor in cancer patients, with skeletal muscle loss and high adiposity associated with poorer prognosis. This study evaluated how body composition affects treatment efficacy in 48 women with metastatic breast cancer receiving trastuzumab deruxtecan. Using computed tomography, skeletal muscle, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed within 60 days before initiating treatment. High SAT and VAT areas were significantly associated with a higher likelihood of dose reductions (Odds Ratio [OR] = 5.34, p = .032 and OR = 5.52, p = 0.032, respectively). Higher SAT areas correlated with a lower objective response rate (OR = 0.22, p = 0.047). Medium SAT and low/medium VAT densities increased the risk of dose reductions. A body mass index over 25 kg/m<sup>2</sup> was linked to higher dose reductions (OR = 4.97, p = 0.016). These findings emphasize the need for personalized treatment strategies based on body composition.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"38"},"PeriodicalIF":6.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ Breast CancerPub Date : 2025-04-22DOI: 10.1038/s41523-025-00752-9
Valentina Cutano, Ming Li Chia, Eleanor M Wigmore, Lorna Hopcroft, Stuart C Williamson, Amanda L Christie, Brandon Willis, James Kerr, Jenny Ashforth, Rhys Fox, Sophie D'Arcy, Lauren Bradshaw, Catherine Blaker, Cath Eberlein, Lambert Montava-Garriga, Elza C de Bruin, Susan E Critchlow, Kevin M Brindle, Simon T Barry, Susana Ros
{"title":"The interplay between FOXO3 and FOXM1 influences sensitivity to AKT inhibition in PIK3CA and PIK3CA/PTEN altered estrogen receptor positive breast cancer.","authors":"Valentina Cutano, Ming Li Chia, Eleanor M Wigmore, Lorna Hopcroft, Stuart C Williamson, Amanda L Christie, Brandon Willis, James Kerr, Jenny Ashforth, Rhys Fox, Sophie D'Arcy, Lauren Bradshaw, Catherine Blaker, Cath Eberlein, Lambert Montava-Garriga, Elza C de Bruin, Susan E Critchlow, Kevin M Brindle, Simon T Barry, Susana Ros","doi":"10.1038/s41523-025-00752-9","DOIUrl":"https://doi.org/10.1038/s41523-025-00752-9","url":null,"abstract":"<p><p>Loss of PTEN expression, via homozygous or hemizygous deletion, is common in PIK3CA mutant ER + BC tumors. We assessed reduction of PTEN protein expression on AKT inhibitor capivasertib efficacy in PIK3CA altered tumors. In PIK3CA altered, PTEN protein high models, PI3Kα and AKT inhibition was effective, however ablation and partial PTEN expression reduction attenuated PI3Kαi but not AKTi efficacy, alone or combined with fulvestrant. Efficacy was FOXO3 dependent and associated with FOXM1 downregulation. FOXO3A deletion reduced response to capivasertib, and increased FOXM1 expression. Long term capivasertib exposure of ER+ BC cells upregulated FOXM1 expression. Downregulating FOXM1 expression reversed resistance to capivasertib, while FOXM1 overexpression reduced capivasertib efficacy. Collectively this suggests the AKT-FOXO3-FOXM1 axis plays a pivotal role in response to AKTi in ER+ breast cancer with PIK3CA mutations with and without expression of PTEN, that FOXO3 expression loss can mediate resistance, and that FOXM1 downregulation is a potential biomarker of response.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"36"},"PeriodicalIF":6.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ Breast CancerPub Date : 2025-04-18DOI: 10.1038/s41523-025-00750-x
Santhosh Kumar Karthikeyan, Darshan S Chandrashekar, Snigdha Sahai, Sadeep Shrestha, Ritu Aneja, Rajesh Singh, Celina G Kleer, Sidharth Kumar, Zhaohui S Qin, Harikrishna Nakshatri, Upender Manne, Chad J Creighton, Sooryanarayana Varambally
{"title":"MammOnc-DB, an integrative breast cancer data analysis platform for target discovery.","authors":"Santhosh Kumar Karthikeyan, Darshan S Chandrashekar, Snigdha Sahai, Sadeep Shrestha, Ritu Aneja, Rajesh Singh, Celina G Kleer, Sidharth Kumar, Zhaohui S Qin, Harikrishna Nakshatri, Upender Manne, Chad J Creighton, Sooryanarayana Varambally","doi":"10.1038/s41523-025-00750-x","DOIUrl":"https://doi.org/10.1038/s41523-025-00750-x","url":null,"abstract":"<p><p>Breast cancer (BCa), a leading malignancy among women, is characterized by morphological and molecular heterogeneity. While early-stage, hormone receptor, and HER2-positive BCa are treatable, triple-negative BCa and metastatic BCa remains largely untreatable. Advances in sequencing and proteomic technologies have improved our understanding of the molecular alterations that occur during BCa initiation and progression and enabled identification of subclass-specific biomarkers and therapeutic targets. Despite the availability of abundant omics data in public repositories, user-friendly tools for multi-omics data analysis and integration are scarce. To address this, we developed a comprehensive BCa data analysis platform called MammOnc-DB ( http://resource.path.uab.edu/MammOnc-Home.html ), comprising data from more than 20,000 BCa samples. MammOnc-DB facilitates hypothesis generation and testing, biomarker discovery, and therapeutic targets identification. The platform also includes pre- and post-treatment data, which can help users identify treatment resistance markers and support combination therapy strategies, offering researchers and clinicians a comprehensive tool for BCa data analysis and visualization.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"35"},"PeriodicalIF":6.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ Breast CancerPub Date : 2025-04-15DOI: 10.1038/s41523-025-00748-5
Laura A Huppert, Reshma Mahtani, Samantha Fisch, Naomi Dempsey, Sarah Premji, Angelina Raimonde, Saya Jacob, Laura Quintal, Michelle Melisko, Jo Chien, Ana Sandoval, Lauren Carcas, Manmeet Ahluwalia, Natasha Harpalani, Jenna Hoppenworth, Anne Blaes, Kelly Blum, Mi-Ok Kim, Dame Idossa, Ruta Rao, Karthik V Giridhar, Hope S Rugo
{"title":"Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC).","authors":"Laura A Huppert, Reshma Mahtani, Samantha Fisch, Naomi Dempsey, Sarah Premji, Angelina Raimonde, Saya Jacob, Laura Quintal, Michelle Melisko, Jo Chien, Ana Sandoval, Lauren Carcas, Manmeet Ahluwalia, Natasha Harpalani, Jenna Hoppenworth, Anne Blaes, Kelly Blum, Mi-Ok Kim, Dame Idossa, Ruta Rao, Karthik V Giridhar, Hope S Rugo","doi":"10.1038/s41523-025-00748-5","DOIUrl":"https://doi.org/10.1038/s41523-025-00748-5","url":null,"abstract":"<p><p>Antibody drug conjugates (ADCs) have improved outcomes for patients with metastatic breast cancer (MBC), but there is little data about the sequential use of these agents. In this multicenter retrospective cohort study, we identified 84 patients with HER2-low MBC treated sequentially with trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in either order at 5 institutions between 2020-2024. We evaluated clinical parameters associated with time to treatment failure (TTF) and real-world overall survival (rwOS). Median TTF was longer for ADC1 than ADC2, irrespective of HR-status, ADC sequence order, age ≤65 or >65 years, presence of visceral disease, or use of an intervening therapy. Younger age, longer time from MBC diagnosis to start of ADC1, and receipt of SG as ADC1 were associated with longer rwOS from start of ADC1. This cohort represents one of the first multicenter retrospective series of patients treated with sequential ADCs for HER2-low MBC, which may inform clinical practice.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"34"},"PeriodicalIF":6.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ Breast CancerPub Date : 2025-04-02DOI: 10.1038/s41523-025-00747-6
Soong June Bae, Sohyun Moon, Yoonwon Kook, Seung Ho Baek, Minji Lee, Jee Hung Kim, Sung Gwe Ahn, Joon Jeong
{"title":"Clinical relevance of clinical treatment score post-5 years (CTS5) in HR-positive, HER2-positive breast cancer.","authors":"Soong June Bae, Sohyun Moon, Yoonwon Kook, Seung Ho Baek, Minji Lee, Jee Hung Kim, Sung Gwe Ahn, Joon Jeong","doi":"10.1038/s41523-025-00747-6","DOIUrl":"10.1038/s41523-025-00747-6","url":null,"abstract":"<p><p>There is currently no reliable predictive tool for late recurrence in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study aimed to explore the potential of the clinical treatment score post-5l̥years (CTS5) as a predictive tool for long-term survival beyond 5 years in patients with specifically HR-positive, HER2-positive breast cancer. We collected patient-level data from the HERceptin Adjuvant (HERA) (BIG1-01; ClinicalTrials.gov identifier: NCT00045032) trial. Our investigation focused on assessing the risk of late distant recurrence (DR) and overall survival (OS) according to the CTS5 risk score as continuous value and CTS5 stratification risk groups. A total of 1,818 patients with HR-positive, HER2-positive breast cancer were included in this analysis. The CTS5 score, as a continuous variable, emerged as an independent prognostic factor for both late DR (adjusted HR, 2.05; 95% CI, 1.63-2.58; P < 0.001) and OS (adjusted HR, 2.02; 95% CI, 1.58-2.58; P < 0.001), respectively. In addition, multivariable analysis showed a significant association between the high-risk group and adverse outcomes in late DR (adjusted HR, 2.76; 95% CI, 1.84-4.13; P < 0.001) and OS (adjusted HR, 2.44; 95% CI, 1.59-3.73; P < 0.001) compared to low/intermediate group. Consistent results were observed, regardless of age or administration of HER2-targeted therapy. CTS5 is a useful prognostic tool for predicting late DR and OS in HR-positive, HER2-positive breast cancer patients. Extension of endocrine therapy should be actively considered in patients with CTS5 high-risk group.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"33"},"PeriodicalIF":6.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11965345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NPJ Breast CancerPub Date : 2025-03-30DOI: 10.1038/s41523-025-00744-9
Alan D McCrorie, Hilary Stobart, David Dodwell, Stuart A McIntosh, Shelley Potter
{"title":"Mapping the current landscape of locoregional therapy de-escalation trials in early breast cancer: a systematic review.","authors":"Alan D McCrorie, Hilary Stobart, David Dodwell, Stuart A McIntosh, Shelley Potter","doi":"10.1038/s41523-025-00744-9","DOIUrl":"10.1038/s41523-025-00744-9","url":null,"abstract":"<p><p>A systematic review undertaken to map the current landscape of locoregional de-escalation trials to inform future research. Online databases and trial registries were searched to identify ongoing, recently completed or published studies de-escalating surgery or radiotherapy in patients with early breast cancer. 97 trials evaluated de-escalation of surgery or radiotherapy in up to 94,866 participants. Surgery studies more commonly evaluated treatment omission/reduction after neoadjuvant systemic therapy (NST) and de-escalation of nodal treatment. Radiotherapy studies were more frequently biomarker stratified. Patients were rarely involved in study design. Research questions focused on response-adjusted treatment after NST and omission/reduction of locoregional therapy in patients with low- or intermediate-risk disease. Significant duplication was identified with multiple studies addressing similar questions. This systematic review demonstrates that the current de-escalation portfolio is inefficient, lacks patient focus and needs improvement. An internationally collaborative approach using innovative study designs and patient partnership will be essential to address this.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"32"},"PeriodicalIF":6.5,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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