p16 INK4A -deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases

Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16 is deficient in the majority of HER2+ BCBMs. p16 -deficiency as measured by protein immunohistochemistry predicted response to combined tucatini...

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Bibliographic Details
Published in:	Nature communications Vol. 13; no. 1; p. 1473
Main Authors:	Ni, Jing, Kabraji, Sheheryar, Xie, Shaozhen, Wang, Yanzhi, Pan, Peichen, He, Xiaofang, Liu, Zongming, Leone, Jose Palbo, Long, Henry W, Brown, Myles A, Winer, Eric P, Dillon, Deborah A R, Lin, Nancy U, Zhao, Jean J
Format:	Journal Article
Language:	English
Published:	England 18-03-2022
Subjects:	Antineoplastic Agents - therapeutic use Brain Neoplasms - drug therapy Brain Neoplasms - genetics Brain Neoplasms - pathology Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - metabolism Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase Inhibitor p16 - genetics Female Humans Receptor, ErbB-2 - genetics Receptor, ErbB-2 - metabolism
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Summary:	Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16 is deficient in the majority of HER2+ BCBMs. p16 -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.
ISSN:	2041-1723