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Breast cancer, HER2-overexpressing and HER2-low mBC, cancer mortalityAlthough T-DXd, tumor
DISEASE PROGRESSION, BREAST CANCER, TUMOR
Breast cancer is the fifth leading cause of cancer mortalityAlthough T-DXd provides some clinical benefit in patients with HER2-overexpressing and HER2-low mBC, most of them will ultimately experience disease progression and die. Although the overall structure of T-DXd is well defined, several questions remain regarding its mechanisms of action and resistance. These include the impact of HER2 expression and its spatial distribution on drug efficacy; the distribution of T-DXd in the tumor; the potential impact on the tumor microenvironment; and the molecular mechanisms of resistance. Understanding these mechanisms of action and resistance could lead to improved treatment selection for patients and the potential development of more effective combinatorial treatment strategies. To address these questions, we designed DAISY, a phase 2 trial that evaluated T-DXd efficacy in patients with mBC according to HER2 expression levels and explored treatment response and resistance through biomarker analyses of tumor samples at different timepoints.