Self-Study 2025 Release II: Updates in the Treatment of Hormone Receptor-Positive (HR+) Metastatic Breast Cancer

Hormone receptor (HR)-positive breast cancer is the most common breast cancer subtype. Endocrine therapy (ET), usually with a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i), remains the mainstay of first-line treatment in the metastatic setting. Endocrine resistance invariably manifests through intrinsic or acquired resistance mechanisms. Strategies to overcome endocrine resistance include targeting the altered estrogen receptor (ER)-dependent pathway with novel oral selective estrogen receptor degrader (SERDs) such as elacestrant and imlunestrant or inhibiting the phosphatidylinositol 3-kinase (PI3K) / protein kinase B (AKT) / mammalian target of rapamycin (mTOR) pathway with agents such as alpelisib, capivasertib, or inavolisib. The treatment paradigm for patients with endocrine-resistant disease has shifted from single-agent chemotherapy, which confers marginal benefit, to antibody-drug conjugates (ADCs) such as HER2-targeted ADC trastuzumab deruxtecan and trophoblast cell surface antigen 2 (TROP2)-directed ADCs sacituzumab govitecan or datopotamab deruxtecan. In this module, participants will evaluate the recent data behind imlunestrant, inavolisib, trastuzumab deruxtecan, and datopotamab deruxtecan and explore the clinical situations in which the utilization of these agents would be appropriate.