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Article History

Received: 9 March 2026

Accepted: 5 May 2026

First Online: 8 June 2026

Competing interests

: F.-C.B. reports research funding from GE Healthcare, Menarini Silicon Biosystems, Merck KGaA, MSD, Natera, Novartis, Personalis, Pfizer, Prolynx, Roche, SAGA Dx, and Tempus; advisory board participation with AstraZeneca, Carrick, Daiichi-Sankyo, Hengrui, Inatherys, Eli Lilly, Menarini Silicon Biosystems, Novartis, Pfizer, Relay Therapeutics, Roche, and Tempus; speaker honoraria from AstraZeneca, Daiichi-Sankyo, Eli Lilly, Novartis, and Roche; and travel support from AstraZeneca, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, and Roche. C.B. reports institutional research funding from multiple industry partners including Amgen, AstraZeneca, BioNTech, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Gilead Sciences, GlaxoSmithKline, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Regeneron, Roche/Genentech, Seagen, Servier, and Taiho, as well as academic research projects with CPO, PUCRS, LACOG, and GBECAM; consulting or advisory roles, travel support and presentation honoraria from Adium, Novartis, Pfizer, Roche/Genentech, MSD, AstraZeneca, Eli Lilly, Daiichi Sankyo, and Gilead; and stock ownership in Thummi, MEDSir, and CPO. G.B. reports personal fees for consultancy, advisory boards, lectures or travel support from AstraZeneca, Daiichi Sankyo, Eli Lilly, Novartis, Pfizer, Roche, MSD, Gilead, Menarini, Exact Sciences, Seagen, Helsinn, Takeda, and Tethis; institutional research grants from Gilead; and membership of the SERENA-6 Steering Committee. A.M.B. reports consulting roles with AstraZeneca, Pfizer, Novartis, Eli Lilly, Genentech/Roche, Daiichi Sankyo, Merck, Agendia, Puma Biotechnology, Gilead, BriaCell, and Celcuity; research support from Agendia; and stock options in Celcuity and Ataraxis. S.C. reports honoraria for lectures from Novartis, Hoffmann-La Roche, Pfizer, Eli Lilly, AstraZeneca, Gilead, Merck, Daiichi Sankyo, and Exact Sciences; and institutional research grants to BC Cancer from Novartis, Hoffmann-La Roche, Pfizer, Exact Sciences, AstraZeneca, Genentech, Merck, Sanofi, LOXO Oncology, Eli Lilly, Daiichi Sankyo, and Gilead.J.C. reports consulting or advisory roles for Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Eli Lilly, Merck Sharp & Dohme, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Scorpion Therapeutics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, AbbVie, BridgeBio, BioNTech, Biocon, Circle Pharma, Delcath Systems, Hexagon Bio, Bliss Biopharmaceutical, and Relay Therapeutics; honoraria from Roche, Novartis, Eisai, Pfizer, Eli Lilly, Merck Sharp & Dohme, Daiichi Sankyo, AstraZeneca, Gilead, Stemline Therapeutics, and Zuellig Pharma; institutional research funding from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GmbH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffmann-La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, IQVIA, and Queen Mary University of London; stock ownership in MAJ3 Capital, and Leuko (relative); and patents issued and licensed as previously described. M.C. reports consulting fees from AstraZeneca, Celcuity, Menarini-Stemline, Repare Therapeutics, Olaris, BriaCell, Datar Cancer Genetics, and Eli Lilly; honoraria from Pfizer, AstraZeneca, Merck, Iylon, and Menarini-Silicon Biosystems; and research funding from AstraZeneca and Celcuity. G.C. reports consulting fees from Bristol Myers Squibb, Roche, Pfizer, Novartis, Eli Lilly, AstraZeneca, Daiichi Sankyo, Merck, Seagen, Ellipsis, Gilead, and Menarini; honoraria for lectures or presentations from Eli Lilly, Pfizer, Relay Therapeutics, Gilead and Novartis; travel support from Daiichi Sankyo; and research grants from Merck. S.D. reports honoraria from AstraZeneca, Eli Lilly, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Firebird, NewBridge Pharmaceuticals, AbbVie, and Astellas. P.A.F. reports consulting or advisory roles with AstraZeneca, Novartis, Pfizer, Roche, Daiichi Sankyo, Eli Lilly, Amgen, Boehringer Ingelheim, Celgene, Eisai, MSD, Nanostring, Pierre Fabre, Puma Biotechnology, Seattle Genetics, Tesaro, and Genentech; and institutional research support from several of these companies. L.G. reports consulting and advisory roles for AstraZeneca, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Incyte, Novartis, Pfizer, Merck Sharp & Dohme, Menarini Stemline, AbbVie, and Gilead; research funding from the Gilead Foundation, Guardant Health, and AstraZeneca; and travel support from Menarini Stemline, Novartis, Gilead, and Roche. A.G. reports advisory board roles for Pfizer, Eli Lilly, Novartis, Guardant Health, and Araris; and travel support from Totus Medicine and Pfizer. M.I. reports consulting roles for Seattle Genetics, Daiichi Sankyo, AstraZeneca, Menarini Stemline, Gilead Sciences, Novartis, Pfizer, and Rejuveron Senescence Therapeutics; institutional research support from Roche, Inivata Inc., and Natera Inc., unrelated to the present work; and uncompensated roles with the European Organisation for Research and Treatment of Cancer (EORTC). H.I. reports institutional grants or contracts from Chugai, Daiichi Sankyo, AstraZeneca, MSD, and Novartis; consulting fees from Daiichi Sankyo, Chugai, AstraZeneca, Eli Lilly, MSD, Pfizer, Gilead, and CMIC; and honoraria for lectures or presentations from Chugai, AstraZeneca, Eli Lilly, MSD, Pfizer, Gilead, and Myriad Genetics. W.J. reports research grants and honoraria from AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, GlaxoSmithKline, Guardant Health, Janssen, Eli Lilly, Menarini Stemline, Merck Sharp & Dohme, NeoGenomics, Novartis, Pfizer, Roche, Sanofi-Aventis, and Seagen. E.L. reports institutional advisory board roles for AstraZeneca, Gilead, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, and Roche; institutional research funding from Novartis, Pfizer, and Ellipses; steering committee roles for AstraZeneca, Eli Lilly, Novartis, and Roche (no financial interest); royalties related to venetoclax from the Walter and Eliza Hall Institute; and leadership roles with Breast Cancer Trials Australia, Garvan Institute of Medical Research, St Vincent’s Hospital Sydney, and the University of New South Wales. K.K. reports advisory board roles for Genentech/Roche, Gilead, Seattle Genetics, AstraZeneca, Daiichi Sankyo, Puma Biotechnology, Mersana, Menarini Silicon Biosystems, Myovant Sciences, Merck, Eli Lilly, Pfizer, Novartis, ProteinQure, bioTheranostics, Regor, Relay Therapeutics, Bicycle Therapeutics, RayzeBio, and Jazz Pharmaceuticals; and spouse employment with EQRx (prior employee) and ADC Therapeutics. C.X.M. reports consulting fees from Puma Biotechnology, Pathlight, Genentech, Biovica, AstraZeneca, Tempus, Bayer, FoRx Therapeutics, Delphi Diagnostics, Eli Lilly, Novartis, Stemline, and Pfizer; and research funding from Pfizer. E.L.M. reports consulting roles with AstraZeneca, Genentech, Novartis, Eli Lilly, and Aktis. A.J.M. reports consulting roles with BostonGene, GE HealthCare, AstraZeneca, Aptitude Health, PreludeDX, Community Health Media, Agendia, and Stemline; research support from Bristol Myers Squibb, Summit Therapeutics, and Eli Lilly; honoraria from Novartis, Puma Biotechnology, Gilead, Pfizer, OMNI Health, DAVA Oncology, MJH, and Roundtable Oncology; steering committee participation with AstraZeneca and Novartis; and service as Scientific Advisory Board Chair of the Lobular Breast Cancer Alliance. J.O. reports honoraria for consulting or advisory board participation from Aadi Bioscience, Agendia, Amgen, Aptitude Health, AstraZeneca, BioNTech, Bristol Myers Squibb, Daiichi Sankyo, Duality, Eisai, Eli Lilly, Ellipses, Exact Sciences, G1 Therapeutics, Genentech, Gilead Sciences, Guardant Health, Hibercell, Jazz Pharmaceuticals, Johnson & Johnson, Menarini Stemline, Merck, Mersana, Natera, Novartis, Pfizer, Pierre Fabre Pharmaceuticals, Puma Biotechnology, RayzeBio, Roche, Sanofi, Seagen, Stemline Therapeutics, Summit Therapeutics, Tempus, and TerSera Therapeutics. Y.H.P. reports research funding from MSD, AstraZeneca, Pfizer, Gencurix, Roche, Inocras, and Novartis; consulting or advisory roles with AstraZeneca, MSD, Pfizer, Eisai, Eli Lilly, Roche, Gilead, Daiichi Sankyo, Menarini, Everest Medicines, and Novartis; speaker honoraria from AstraZeneca, MSD, Pfizer, Roche, Eli Lilly, Daiichi Sankyo, Novartis, Gilead, and Helsinn; travel support from Gilead, AstraZeneca, and Pfizer; advisory board participation with AstraZeneca, Menarini, Pfizer, Novartis, Roche, Daiichi Sankyo, and Helsinn; and receipt of materials or other services from Dong-A ST, Sanofi, Roche, and Pfizer. J.P. reports research grants to IBIMA from AstraZeneca and Roche; personal fees for advisory board or speaker roles from AstraZeneca, Gilead, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, and Stemline Therapeutics; and travel support from AstraZeneca, Gilead, Novartis, and Pfizer. P.R. reports institutional research funding from Grail, Novartis, AstraZeneca, Invitae, bioTheranostics, Tempus, NeoGenomics, Guardant Health, Personalis, Myriad Genetics, Foresight Diagnostics, Natera, Biodesix, SAGA Diagnostics, SOPHiA Genetics, Haystack, and Roche; and consulting or advisory board roles and honoraria from Novartis, AstraZeneca, Eli Lilly/Loxo Oncology, Stemline Therapeutics, Prelude Therapeutics, NeoGenomics, Regor Pharmaceuticals, SAGA Diagnostics, SOPHiA Genetics, Tempus, Myriad Genetics, Foresight Diagnostics, Natera, Pathos AI, and BioNTech. S.S. reports research funding from Alterome, Iambic, Ensem, Loxo Oncology, Seagen, Relay Therapeutics, Sermonix, Eli Lilly, AstraZeneca, DSI, and Stemline/Menarini; and consulting or advisory board roles for Eli Lilly, AstraZeneca, Gilead, Sermonix, Seagen, Pfizer, Novartis, and Daiichi Sankyo. P.T. reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eli Lilly, Gilead, Genentech/Roche, Novartis, Menarini/Stemline, Merck, and Sanofi. S.A.W. reports consulting and advisory board roles with Foundation Medicine, Veracyte, Hologic, Eli Lilly, Biovica, Pfizer, Arvinas, Puma Biotechnology, Novartis, AstraZeneca, Genentech, Regor Therapeutics, Stemline/Menarini, Gilead, Celcuity, Precede Biosciences, Halda Therapeutics, and Boundless Bio; educational or speaking activities for Eli Lilly, Guardant Health, and 2ndMD; and institutional research support from Genentech, Eli Lilly, Pfizer, Arvinas, Nuvation Bio, Regor Therapeutics, Sermonix, Puma Biotechnology, Stemline/Menarini, and Phoenix Molecular Designs. G.W. reports research funding from Astellas Pharma, AstraZeneca, Bayer, GlaxoSmithKline, Merck & Co., Novartis, Pfizer, Roche, Takeda Pharmaceutical, Janssen, and Libbs; consulting or advisory roles for AstraZeneca, Merck & Co., Novartis, Daiichi Sankyo, and Roche; and honoraria for lectures from AstraZeneca, Merck & Co., Novartis, Pfizer, Roche, and Daiichi Sankyo. L.S. and J.L.S. declare no competing interests.