Targeting HER2-low in metastatic breast cancer: an evolving treatment paradigm.

The results of the Phase III DESTINY-Breast04 trial of trastuzumab deruxtecan (T-DXd) are leading to a shift in both the classification and treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. In this trial, T-DXd was associated with a substantial survival benefit among patients with hormone receptor-positive and hormone receptor-negative disease and low expression of HER2, a biomarker previously considered unactionable in this treatment setting. Herein, we discuss the evolving therapeutic pathway for HER2-low disease, ongoing clinical trials, and the potential challenges and evidence gaps arising with treatment of this patient population.

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© The Author(s), 2023.

Déclaration de conflit d'intérêts

CY had no conflicts to disclose. CB-M reports serving in a consultancy or advisory role and receiving honoraria from Amgen, AstraZeneca, BMS, Eli Lilly, Gilead, Knight Therapeutics, Mylan, Novartis, Pfizer, Roche, Seagen, and Taiho and has received research funding from Eli Lilly and AstraZeneca. AAJ has served in a consultancy or advisory role and has received honoraria from AstraZeneca, BMS, Eli Lilly, Gilead, Knight Therapeutics, Mylan, Novartis, Pfizer, Roche, and Teva. SS reports participating in advisory boards and/or receiving speaker fees from AstraZeneca, Gilead, Roche, Novartis, and Merck. SM has been a scientific advisor for AstraZeneca, Daiichi Sankyo, Eli Lilly, Genentech, Gilead, GlaxoSmithKline, Macrogenics, Puma Biotechnology, Seagen, and Zymeworks. SM also reports attending speaking engagements for AstraZeneca, Daiichi Sankyo, Genentech, Novartis, and Seagen and being a primary investigator on trials for AstraZeneca, Daiichi Sankyo, Genentech, and Seagen. CS has served in a consultancy or advisory role and received honoraria from Eli Lilly, Mylan, Pfizer, and Roche, and CS has received research funding from AstraZeneca Global, Knight Therapeutics, Roche, Pfizer, and Viatris. J-WH reports serving in a consultancy or advisory role and receiving honoraria from AstraZeneca, Eli Lilly, Knight Therapeutics, Mylan, Novartis, Pfizer, Roche, and Seagen. J-WH also reports having speaking arrangements with Gilead and receiving research grant support from AstraZeneca, Novartis, and Pfizer.