P16^INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases.

ABSTRACT: Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16^INK4A is deficient in the majority of HER2+ BCBMs. p16^INK4A-deficiency as measured by protein immunohistochemistry predicted response to combined tucatinib and abemaciclib in orthotopic patient-derived xenografts (PDXs) of HER2 + BCBMs. Our findings establish the rationale for a biomarker-driven clinical trial of combined CDK4/6- and HER2-targeted agents for patients with HER2 + BCBM.

SUBMITTER: Ni J 

PROVIDER: S-EPMC8933392 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature