Long-term risk of recurrence (RoR) among real-world patients (pts) with hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (EBC) with N1 disease

Abstract

Background: Despite endocrine therapy (ET), RoR remains a concern among pts with HR+/HER2- EBC. The N1 cohort of pts with EBC represents a heterogeneous group at high RoR over time, comprising pts with varying risk factors including age and menopausal status, tumor grades, and anatomical stages. This study assessed cumulative RoR over a 5- and 10-y period for a cohort of pts with HR+/HER2- EBC and N1 disease with differing risk factors. Method(s): Pts with stage II/III HR+/HER2- EBC with N1 (including N1mi) disease, treated with ET, from the Flatiron Health Panoramic BC database were included (initial diagnosis, Jan 1, 2011-Oct 31, 2020). Data cutoff was Oct 31, 2025, ensuring extracted data covered >=5y of potential follow-up. Pts were analyzed as high-risk early recurrence (N1 with T>=5 cm or G3 in stage II/III) or high-risk late recurrence (N1 with T<5 cm and G<3 in stage II/III). Recurrence-free survival (RFS; any locoregional recurrence, distant recurrence, or death) and distant recurrence (any event involving distant recurrence only, excluding mortality) were assessed. Result(s): Of 45,236 pts with N1 disease, 15,971 were high-risk early recurrence vs 29,265 who were high-risk late recurrence: median age, 58y vs 61y; postmenopausal, 65.7% vs 72.3%; stage II, 62.6% vs 100%; and T1, 19.8% vs 46.9%. Median follow-up duration from initial diagnosis to last activity was 6.6y and to the data cutoff was 9.5y. In both the N1 high-risk early and N1 high-risk late recurrence groups, a substantial proportion of pts experienced a distant recurrence event along with a reduced probability of RFS at both 5y and 10y (Table). [Formula presented] Conclusion(s): Despite heterogeneity in disease characteristics, all N1 pts on ET experienced substantial RoR over the short and long term. These data highlight the need to consider RoR beyond 5y and for treatment beyond ET to manage the risk of both early and late recurrences for this pt group. Editorial acknowledgement: Medical editorial assistance with earlier versions of this abstract was provided by Shashank Tandon of Nucleus Global. Legal entity responsible for the study: Novartis Pharmaceuticals Corporation. Funding(s): Novartis Pharmaceuticals Corporation. Disclosure: K. Jhaveri: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, AbbVie, Seattle Genetics, Daiichi Sankyo, Lilly Pharmaceuticals/Loxo Oncology, Gilead, Blueprint Medicines, Biotheranostics, Bicycle Therapeutics, Merck, Olema Pharmaceuticals, Eisai, Rayzebio, Halda Therapeutics, Scorpion Therapeutics, Menarini-Stemline; Financial Interests, Personal, Other, Consultant: Pfizer, Genentech; Financial Interests, Institutional, Invited Speaker: Novartis, Pfizer, AstraZeneca, Lilly Pharmaceuticals, Genentech, Zymeworks, Gilead, Puma Biotechnology, Merck Pharmaceuticals, Blueprint Medicines, Rayzebio, Scorpion Therapeutics, Bicycle Therapeutics; Non-Financial Interests, Other, Steering Committee Member: Genentech. J.A. O'Shaughnessy: Financial Interests, Personal, Advisory Board: Agendia, Amgen, Aptitude Health, AstraZeneca, Eisai, G1 Therapeutics, Lilly, Merck, Novartis, Pfizer, Puma, Roche, Daiichi Sankyo, Gilead Sciences, Pierre Fabre Pharmaceuticals, Sanofi, BioNtech, Dava Oncology, Genentech, Seagen, Stemline Therapeutics, Duality, Bristol Myers Squibb, Ellipses, Exact Science, Guardant Health, Hibercell, Jazz Pharmaceuticals, Johnson and Johnson, Menarini-Stemline, Mersana Therapeutics, Natera, Summit Therapeutics, Tempus, TerSera Therapeutics, AADI Bioscience. K. Kalinsky: Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Eli-Lilly, Pfizer, Novartis, AstraZeneca, Merck, Seattle Genetics, Puma, Genentech, Gilead, Menarini, myovant, Takeda, Mersana Therapeutics, proteinqure, biotheranostics, Regor, Relay Therapeutics; Financial Interests, Personal, Stocks/Shares, Employment + Stock = spouse: Grail; Financial Interests, Personal, Stocks/Shares, Spouse: ADC Therapeutics; Financial Interests, Personal and Institutional, Invited Speaker, Consultant: Novartis, Eli-Lilly, AstraZeneca, daicchi sankyo; Financial Interests, Personal and Institutional, Invited Speaker, consultant: Genentech; Financial Interests, Institutional, Invited Speaker, consultant: Pfizer; Financial Interests, Institutional, Invited Speaker: Seattle Genetics, Ascentantage; Financial Interests, Personal, Other, Consultant: Myovant, Takeda, Menarini, Prelude; Financial Interests, Personal, Other, consultant: RayzeBio; Other, Other, Support for attending meetings and/or travel: Eli-Lilly, AstraZeneca, Pfizer; Other, Other, Steering Committee: Immunomedics, AstraZeneca, Ambryx, Genentech. P. Tarantino: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca, Daiichi Sankyo, Genentech, Eli Lilly, Gilead, Novartis; Financial Interests, Institutional, Funding: AstraZeneca. M. De Laurentiis: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Roche, AstraZeneca, Eisai, Eli Lilly, MSD, Pierre Fabre, Exact Science, Daiichi-Sankyo, Gilead, Seagen, Menarini-Stemline, Veracyte, Takeda, Ipsen. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Pfizer, Roche, Gilead, Daiichii Sankyo, MSD, Bicycle Therapeutics, Lilly, Summit Therapeutics, Olema Oncology; Financial Interests, Personal, Invited Speaker: Menarini-Stemline, Gilead, AstraZeneca, Daiichii Sankyo, MSD, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Genentech, Roche. C.H.E. Barrios: Financial Interests, Personal, Advisory Board, CONSULTING SCIENTIFIC PRESENTATIONS: NOVARTIS, PFIZER, ROCHE, MSD, ASTRAZENECA, LILLY; Financial Interests, Personal, Advisory Board, Scientific Presentations Consulting AD Board: Daiichi Sankyio; Financial Interests, Personal, Invited Speaker, Consulting Scientific presentations: GILEAD; Financial Interests, Personal, Advisory Board, Consulting and speaker: ADIUM; Financial Interests, Personal, Ownership Interest, Clinical Research Company: Centro de Pesquisa em Oncologia - CPO; Financial Interests, Personal, Ownership Interest, App: Thummi; Financial Interests, Personal, Stocks/Shares, Clinical research company: Medsir; Financial Interests, Institutional, Research Grant, RESEARCH FUNDING TO THE INSTITUTION: PFIZER, AMGEM, GSK, LILLY, MERCK, BMS, MERCK KGAA, PHARMAMAR; Financial Interests, Institutional, Research Grant, RESEARCH FUNDING TO THE INSTITUTIONSteering Committee: NOVARTIS, ASTRAZENECA, DAIICHI; Financial Interests, Institutional, Research Grant, RESEARCH FUNDING TO THE INSTITUTIONSteering committee: ROCHE; Financial Interests, Institutional, Invited Speaker, Research funding to the institution: Janssen, OBI Pharma, Seagen, Novocure, Aveo Oncology, PPD, Syneos health, Labcorp, IQIVIA, Parexel, Nuvisan, Medplace; Financial Interests, Institutional, Research Grant, Research grant to the institution: Fortrea, Tolmar, Worldwide; Financial Interests, Institutional, Research Grant, Research Grant to the Institution: Dizal Pharma; Financial Interests, Institutional, Research Grant, Research Grant to the institution: Stemline, SAMSUNG, ICON, Biontech, Taiho; Financial Interests, Institutional, Invited Speaker, Research grant to Institution: TRIO; Financial Interests, Institutional, Invited Speaker, Research grant To the institution: BeiGene; Financial Interests, Institutional, Invited Speaker, Research Grant to the Institution: Bicycle Therapeutics, Boehringer Ingelheim, Celltrion, Gilead Sciences, Jazz Pharmaceuticals, Merus, Mirati Terapeutic, Sandoz, Servier, Shangai Henlius, Intrails, Regeneron, MSD; Financial Interests, Institutional, Invited Speaker, Research grant to the institution: Cellcuity; Financial Interests, Institutional, Invited Speaker, Research Grant to the institution: Genmab, mAbxience Research; Non-Financial Interests, Leadership Role, Latin American Cooperative Oncology Group: LACOG; Non-Financial Interests, Other, Past Chair, International Educational Steering Group: ASCO; Non-Financial Interests, Advisory Role, Member Compliance Committee: ESMO. F. Cardoso: Financial Interests, Personal, Other, Consultancy: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, GSK, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, Prime Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva; Financial Interests, Personal, Advisory Board: Gilead, Iqvia, Touchime; Financial Interests, Personal, Advisory Board, Advisory Boards: Bayer; Financial Interests, Institutional, Invited Speaker: Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers-Squibb, Bayer, Daiichi, Eisai, Fresenius GmbH, Genentech, GSK, Ipsen, Incyte, Nektar Therapeutics, Nerviano, Novartis, Macrogenics, Medigene, MedImmune, Merck, Millenium, Pfizer, Pierre-Fabre, Roche, Sanofi-Aventis, Sonus, Taiho Oncology, Tesaro, Tigris, Wilex, Wyeth, Gilead; Financial Interests, Institutional, Invited Speaker, PI in clinical trials: Bayer; Financial Interests, Institutional, Invited Speaker, Local PI or investigator in clinical trials: Seagen; Non-Financial Interests, Leadership Role, President: ABC Global Alliance and ABC Consensus Conference and Guidelines; Non-Financial Interests, Member: ESMO, ESO, EORTC, BCG, IBCSG, SOLTI, ASCO, AACR, EACR, SIS, ASPIC, European Cancer Organisation, AORTIC, UICC, Portuguese Society of Medical Oncology (SPO); Non-Financial Interests, Other, Fellow of the European Academy of Cancer Sciences: European Academy of Cancer Sciences; Non-Financial Interests, Advisory Role: EVITA. J. Kim: Financial Interests, Personal, Full or part-time Employment: Genesis Research Group. J. Collins: Financial Interests, Personal, Full or part-time Employment: Novartis. V. Ganapathy: Financial Interests, Personal, Full or part-time Employment: Novartis. F. Ye: Financial Interests, Personal, Full or part-time Employment: Novartis. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Lilly, Mersana, Stemline Therapeutics, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Other, Consulting: Accutar Biotechnology, Entos, Gilead Sciences, Jazz Pharmaceuticals, Jefferies LLC, Medical Pharma Services, Tempus Labs, Zentalis Pharmaceuticals, Arvinas, BeiGene, Circle Pharma, Incyclix Bio, IQVIA, Janssen, Johnson and Johnson, Pyxis Oncology, Samsung Bioepis, Shorla Pharma, Halda Therapeutics, Novartis, Pfizer; Financial Interests, Institutional, Invited Speaker: Genentech/Roche, Zymeworks, Rgenix, Novartis, FujiFilm, Taiho, SeaGen, Compugen, Lilly, Pfizer, H3 Biomedicine, Regeneron, Arvinas, Verastem, InventisBio, Mersana, AbbVie, Orinove, AstraZeneca, Tesaro, Daiichi Sankyo, Sutro, Olema, Immunogen, Shattuck Labs, Atlas MedX, Ellipses Pharma, Jacobio, Mabspace Biosciences, Pionyr Immunotherapeutics, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Cullinan, Dantari, Duality Biologics, Elucida Oncology, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Gilead Sciences, Inspirna, Stemline Therapeutics, Bicycle Therapeutics, Biohaven Pharmaceuticals, BioNTech, Day One Biopharmaceuticals, Exelixis, Genmab, Iambic Therapeutics, Jazz Pharmaceuticals, Mabwell Bioscience, Marengo Therapeutics, MediLink Therapeutics, Merck, Simcha Therapeutics, Systimmune, TheRas, Xadcera Biopharmaceutical. All other authors have declared no conflicts of interest. Copyright © 2026