Evolution of HER2 expression between pre-treatment biopsy and residual disease after neoadjuvant therapy for breast cancer
- PMID: 38368741
- DOI: 10.1016/j.ejca.2024.113920
Evolution of HER2 expression between pre-treatment biopsy and residual disease after neoadjuvant therapy for breast cancer
Abstract
Introduction: We have previously found that HER2 expression is dynamic, and can change from the primary breast tumor to matched recurrences. With this work, we aimed to assess the dynamics of HER2 during neoadjuvant treatment.(NAT).
Methods: We reviewed HER2 expression in pre- and post-treatment samples from consecutive patients with early-stage breast cancer that received NAT and underwent surgery at Dana-Farber Brigham Cancer Center between 01/2016-08/2022. The primary outcome was evolution of HER2 expression from pre- to post-NAT specimens in patients with residual disease.
Results: Among 1613 patients receiving NAT, 1080 had residual disease at surgery. A total of 319 patients (29.5%) experienced a change in HER2 expression (HER2 0 vs. HER2-low vs. HER2-positive) from the pre-treatment sample to residual disease, with roughly equal distribution between decreased (50.5%) and increased HER2 expression (49.5%). Similar rates of change in HER2 expression were observed with anthracycline-based (31.8%) or taxane/platinum-based regimens (32.4%). Patients with HER2-0 or HER2-low tumors at diagnosis were likelier to experience a change in HER2 expression post-NAT compared to HER2-positive (32.3% vs. 21.3%, p < 0.001). Changes in HER2 expression post-NAT were prognostic among patients with HER2-positive tumors at diagnosis (3-year recurrence-free survival for change vs. no change: 71.6% vs. 89.6%, p = 0.006) but not among those with HER2-negative tumors at diagnosis (3-year recurrence-free survival for change vs. no change: 79.3% vs. 81.1%, p = 0.31).
Conclusions: Nearly 30% of patients with early-stage breast cancer showed a change in HER2 expression after NAT. Changes in HER2 expression post-NAT were only prognostic in the setting of HER2-positive tumors becoming HER2-negative at surgery.
Keywords: Breast cancer; HER2 dynamics; HER2-low; Neoadjuvant treatment.
Copyright © 2024 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest PT served as advisor/consultant for AstraZeneca, Daiichi-Sankyo, Gilead, Genentech, Roche, Eli Lilly. TAK reports speaker honoraria and compensated service on the scientific Advisory Board of Exact Sciences. EAM reports compensated service on scientific advisory boards for Astra Zeneca, BioNTech, Exact sciences (formerly Genomic Health), Merck, Moderna, and Roche/Genentech; uncompensated service on steering committees for Bristol Myers Squibb, Lilly, and Roche/Genentech; speakers honoraria and travel support from Merck Sharp & Dohme; and institutional research support from Roche/Genentech (via SU2C grant) and Gilead. EAM also reports research funding from Susan Komen for the Cure, for which she serves as a Scientific Advisor, and uncompensated participation as a member of the American Society of Clinical Oncology Board of Directors. NUL reports consulting honoraria from Puma, Seattle Genetics, Daiichi-Sankyo, AstraZeneca, Olema Pharmaceuticals, Janssen, Blueprint Medicines, Stemline/Menarini, Artera Inc., and Eisai; institutional research funding from Genentech (and Zion Pharmaceutical as part of GNE), Pfizer, Merck, Seattle Genetics (now Pfizer), Olema Pharmaceuticals, and AstraZeneca; royalties from UptoDate (book); and travel support from Olema Pharmaceuticals. SMT has served as an advisor/consultant to Novartis, Pfizer, Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, Seattle Genetics, CytomX Therapeutics, Daiichi-Sankyo, Gilead, OncXerna, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, ARC Therapeutics, Infinity Therapeutics, Suvitovant Biopharma, Zetagen, Umoja Biopharma, Artios Pharma, Menarini/Stemline, Aadi Biopharma, Bayer, Incyte Corp, Jazz Pharmaceuticals, Natera, Tango Therapeutics, Systimmune, eFFECTOR, and Hengrui USA; has received institutional research funding from Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, NanoString Technologies, Seattle Genetics, and OncoPep; and has received travel support from Eli Lilly, Sanofi, Gilead, and Pfizer. GC reports honoraria for speaker's engagements at Roche, Seattle Genetics, Novartis, Lilly, Pfizer, Foundation Medicine, NanoString, Samsung, Celltrion, Bristol Myers Squibb, and MSD; honoraria for providing consultancy to Roche, Seattle Genetics, and NanoString; honoraria for participating on the Advisory Boards of Roche, Lilly, Pfizer, Foundation Medicine, Samsung, Celltrion, and Mylan; honoraria for writing engagements for Novartis and Bristol Myers Squibb; honoraria for participation in the Ellipsis Scientific Affairs Group; and institutional research funding for conducting phase I and II clinical trials for Pfizer, Roche, Novartis, Sanofi, Celgene, Servier, Orion, AstraZeneca, Seattle Genetics, AbbVie, Tesaro, Bristol Myers Squibb, Merck Serono, Merck Sharp Dome, Janssen-Cilag, Philogen, Bayer, Medivation, and Medimmune. ACGC reports research funding (to institution) from AstraZeneca, Daiichi-Sankyo, Merck, Gilead Sciences, and Zenith Epigenetics; and travel accommodations from Roche/Genentech. The remaining authors declare no conflicts of interest.
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