Unraveling Vulnerabilities in Endocrine Therapy-Resistant HER2+/ER+ Breast Cancer

Breast tumors overexpressing human epidermal growth factor receptor (HER2) confer intrinsic resistance to endocrine therapy (ET), and patients with HER2/ estrogen receptor-positive (HER2+/HR+) breast cancer (BCa) are less responsive to ET than HER2+/ER-. However, real-world evidence reveals that a large subset of HER2+/ER+ patients receive ET as monotherapy, signifying this treatment pattern as a clinical challenge. In the present study, we developed and characterized two distinct in vitro models of ET-resistant (ETR) HER2+/ER+ BCa to identify possible therapeutic liabilities.