Navigating uncertainties and evidence gaps in adjuvant therapy for premenopausal women with HR+/HER2- breast cancer

Premenopausal women with hormone receptor–positive (HR+)/HER2-negative early breast cancer represent a clinically distinct population, characterized by more aggressive tumor biology, unique survivorship concerns, and complex treatment decision-making. Although evidence from dedicated trials and subgroup analyses is available, management remains challenging because data are heterogeneous, evolving, and often extrapolated from broader populations that include predominantly postmenopausal women. Adjuvant endocrine therapy, with the addition of CDK4/6 inhibitors in selected higher-risk patients, remains the cornerstone of treatment; however major uncertainties persist regarding the optimal use of ovarian function suppression, the interpretation of genomic assays to inform chemotherapy decisions, the selection of candidates for extended endocrine therapy, and the management of adherence, treatment-related toxicities, pregnancy-related issues, and survivorship concerns. Here, we synthesize current evidence across these domains and propose a pragmatic clinical framework to support individualized treatment strategies and optimize care for this population in the contemporary therapeutic landscape.