Hormone Receptor–Positive/Human Epidermal Growth Receptor 2–Negative Metastatic Breast Cancer in Young Women: Emerging Data in the Era of Molecularly Targeted Agents

Breast cancer is the most common malignancy in young women worldwide, accounting for an estimated 30% of new cancer diagnoses and 25% of cancer deaths. Approximately two thirds of young women with breast cancer have hormone receptor–positive (HR+)/human epidermal growth receptor 2–negative (HER2−) tumors. Numerous studies, primarily in early-stage breast cancer, have demonstrated that young age is an independent risk factor for more aggressive disease and worse outcomes. Although more limited data are available regarding outcomes in young patients with advanced disease, these age-related disparities suggest that breast cancer in premenopausal women has distinct clinicopathologic and molecular features that can impact treatment outcomes. Until recently, limited data were available on the intrinsic molecular subtypes and genetics of young patients with HR+/HER2− metastatic breast cancer (mBC). In this review, we explore insights into the clinical and pathologic features of HR+/HER2− mBC in younger women derived from recent clinical trials of the cyclin-dependent kinase 4/6 inhibitors palbociclib (PALOMA-3), ribociclib (MONALEESA-7), and abemaciclib (MONARCH 2) and the implications of these findings for clinical practice, guideline development, and future research. Implications for Practice: This review provides clinicians with an overview of emerging data on the unique clinicopathologic and molecular features of hormone receptor–positive/human epidermal growth receptor 2–negative metastatic breast cancer (mBC) in premenopausal women, summarizes findings from the most recent clinical trials of endocrine-based treatment in this patient population, and explores the implications of these findings for clinical practice, guideline development, and future research. Improved understanding of the key factors influencing disease course and treatment response in premenopausal patients with mBC may lead to more timely incorporation of evidence-based treatment approaches, thereby improving patient care and outcomes.