Adjuvant endocrine therapy in high-risk HR-positive and HER2-negative early breast cancer

Hormone receptor-positive (HR+) and HER2-negative (HER2−) early breast cancer (EBC) accounts for more than 70% of breast cancer diagnoses. Prognostic assessment is traditionally based on clinical and histological criteria, including tumor size, nodal involvement, histologic grade, and measures of tumor proliferation. Multigene expression assays and composite clinicopathological models further refine risk stratification in selected patients, particularly in those with intermediate-risk features, guiding adjuvant therapeutic choices. Adjuvant endocrine therapy (ET), typically with aromatase inhibitors in postmenopausal women or with ovarian suppression combined with either an aromatase inhibitor or tamoxifen in high-risk premenopausal patients, substantially reduces recurrence risk. Nevertheless, 15–30% of patients ultimately relapse, highlighting the need for improved risk stratification and treatment optimization. While extended ET beyond 5 years provides modest additional benefit in selected patients, this strategy must be carefully weighed against toxicity and quality-of-life considerations. The integration of targeted agents, including CDK4/6 inhibitors, into adjuvant ET expands therapeutic options for high-risk HR+/HER2− EBC, illustrating the ongoing treatment personalization. Emerging endocrine agents, such as oral selective estrogen receptor degraders (SERDs) and other next-generation estrogen receptor–targeted agents, aim to overcome endocrine resistance while improving tolerability and long-term adherence. In parallel, adaptive strategies integrating dynamic biomarkers, including genomic profiling and circulating tumor DNA (ctDNA) monitoring, are under active investigation to refine risk stratification and guide response-adapted interventions. Collectively, these advances support a biologically guided, response-adapted approach to optimize long-term outcomes while minimizing overtreatment, reflecting the ongoing shift toward precision oncology in HR+/HER2− EBC.