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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

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p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases.

Ni Jing J Kabraji Sheheryar S Xie Shaozhen S Wang Yanzhi Y Pan Peichen P He Xiaofang X Liu Zongming Z Leone Jose Palbo JP Long Henry W HW Brown Myles A MA Winer Eric P EP Dillon Deborah A R DAR Lin Nancy U NU Zhao Jean J JJ

Nature communications 20220318 1

Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16INK4A is deficient in the majority of HER2+ BCBMs. p16INK4A-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 ...[more]

PMID: 35304445

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