<p>Patients with metastatic HER2-positive (HER2+) breast cancer will frequently develop brain metastases (BCBMs). Here, we report that p16INK4A, a tumor suppressor, is deficient in the majority of HER2+ BCBMs. Furthermore, p16INK4A deficiency, as measured by protein immunohistochemistry, can be a predictive marker associated with response to combined treatment with tucatinib and abemaciclib in our orthotopic patient-derived xenografts (PDXs) models of HER2+ BCBMs. Our findings provide the rationale for a biomarker-driven clinical trial of combined treatment with CDK4/6- and HER2-targeted agents for patients with HER2+ BCBM.  </p>

Combined Targeting of CDK4/6 and HER2 Signaling in Orthotopic    Patient-Derived Xenografts of HER2-Positive Breast Cancer Brain    Metastases

Variables — phs002482 — Combined Targeting of CDK4/6 and HER2 Signaling in Orthotopic    Patient-Derived Xenografts of HER2-Positive Breast Cancer Brain    Metastases

Combined Targeting of CDK4/6 and HER2 Signaling in Orthotopic Patient-Derived Xenografts of HER2-Positive Breast Cancer Brain Metastases

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