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Article History

Received: 18 August 2025

Accepted: 2 June 2026

First Online: 27 June 2026

Declarations

Ethics approval and consent to participate: All samples included in this study were voluntarily donated by patients who provided informed consent under an IRB-approved protocol (Dana-Farber/Harvard Cancer Center no. 05–246) and patient consent in accordance with the Helsinki Declaration. The protocol includes permission for sample acquisition, clinical data abstraction, sample analysis and data sharing. Analysis of biospecimens at the Broad Institute was performed under Broad Institute protocol number 15-370B.All mice were maintained in accordance with local guidelines and therapeutic interventions approved by the Animal Care and Use Committees of Dana-Farber Cancer Institute Protocol # 04-111.

Consent for publication: Not applicable.

Competing interests: AN is an AstraZeneca employee; JGTZ reported ownership of stocks in the biotechnology exchange-traded funds CNCR, IDNA, IBB, and XBI; owns stocks in Novo Nordisk and GRAIL; and previously owned stocks in Adaptive Biotechnologies, 2seventy bio, and bluebird bio; NUL has received research support paid to her institution from Genentech, Pfizer, Merck, Seattle Genetics, Zion Pharmaceuticals, Olema Pharmaceuticals, AstraZeneca. She has received honoraria for consulting work from Seattle Genetics, Daichii-Sankyo, AstraZeneca, Olema Pharmaceuticals, Janssen, Blueprint Medicines, Stemline/Menarini, Eisai, Shorla Oncology. She holds stock options in Artera Inc (unrelated to breast cancer or brain metastases research) and receives royalties from UpToDate (book chapter). She receives travel support from Olema, AstraZeneca and Daichii Sankyo; SMT reports consulting or advisory roles for Novartis, Pfizer/SeaGen, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Bristol Myers Squibb/Systimmune, Daiichi Sankyo, Gilead, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Jazz Pharmaceuticals, Natera, Tango Therapeutics, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas, BioNTech, Launch Therapeutics, Zuellig Pharma, Johnson&Johnson/Ambrx, Bicycle Therapeutics, BeiGene Therapeutics, Mersana, Summitt Therapeutics, Avenzo Therapeutics, Aktis Oncology, Celcuity, Boehringer Ingelheim, Samsung Bioepis, Olema; research funding Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, AstraZeneca, NanoString Technologies, Gilead, SeaGen, OncoPep, Daiichi Sankyo, Menarini/Stemline, Jazz Pharmaceuticals; and travel support from Lilly, Gilead, Jazz Pharmaceuticals, Pfizer, Arvinas, Roche; LM reports advisory role for AstraZeneca, Pfizer, Lilly, Novartis, Seagen, Roche and Menarini, fundings from Pfizer, Novartis and travel grants from Pfizer and Gilead; PS has been a consultant at Novartis, Genovis, Guidepoint, The Planning Shop, ORIC Pharmaceuticals, Cedilla Therapeutics, Syros Pharmaceuticals, Blueprint Medicines, Curie Bio, Differentiated Therapeutics, Excientia, Ligature Therapeutics, Merck, Redesign Science, Scorpion Therapeutics, Incyte, Serinus Biosciences, Meliora Therapeutics, Sibylla Biotech, Exo Therapeutics and Astex Pharmaceuticals; KP serves on the Scientific Advisory Board of Ideaya Biosciences, is an adviser to Curie.Bio and Redona Therapeutics, holds equity in Antares Therapeutics and stock options in Ideaya Biosciences, receives sponsored research funding from Novartis, and received honoraria from Astra-Zeneca in the past 12 months; CP is a consultant for XSphera Biosciences and has stock and other ownership interests in XSphera Biosciences. Received honoraria from Thermo Fisher and Agilent and has sponsored research agreements with Daiichi Sankyo, Bicycle Therapeutics, Transcenta, Bicara Therapeutics, AstraZeneca, Janssen Pharmaceuticals, Array Biopharma, Takeda Onkology, Bristol Meyers Squibb, TargImmune, and Mirati Therapeutics; FM is a co-founder of and has equity in Harbinger Health, has equity in Zephyr AI, and serves as a consultant for both companies. She is also on the board of directors of Recursion Pharmaceuticals. She declares that none of these relationships are directly or indirectly related to the content of this manuscript. GG receives research funds from IBM, Pharmacyclics/Abbvie, Bayer, Genentech, Calico, Ultima Genomics, Inocras, Google, Kite, and Novartis and is also an inventor on patent applications filed by the Broad Institute related to MSMuTect, MSMutSig, POLYSOLVER, SignatureAnalyzer-GPU, MSEye, MinimuMM-seq, and DLBclass. He is a founder, consultant, and holds privately held equity in Scorpion Therapeutics; he is also a founder of, and holds privately held equity in, Predicta Biosciences; and holds privately held equity in Antares Therapeutics. RJ reports consulting or advisory role for Eli Lilly, Astra Zeneca, Pfizer, Novartis, Carrick Therapeutics, GE Health, and Luminex and research funding from Pfizer, Eli Lilly, and Novartis.All other authors declare no competing interests.