Impact of extended endocrine therapy for patients with risk factors for late recurrence in estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer after 5 years of endocrine therapy

Abstract Purpose Extended endocrine therapy shows promise for reducing the recurrence of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, its benefits for patients with high-risk factors for late recurrence remain unclear, particularly for premenopausal patients. This study aimed to explore the impact of extended endocrine therapy on patients with risk factors for late recurrence of postmenopausal and premenopausal ER-positive, HER2-negative breast cancer. Methods We retrospectively analyzed data from patients with ER-positive, HER2-negative breast cancer at Tohoku Kosai Hospital who were disease-free after 5 years of adjuvant endocrine therapy. The patients were classified as high risk based on lymph node positivity, tumor size > 2 cm, or high tumor grade. The high-risk group was further divided into the extended and stop therapy groups. Propensity score matching was applied to balance the baseline characteristics. Disease-free survival (DFS) was the primary endpoint. Results Among the 1,474 eligible patients, 224 received extended endocrine therapy and 1,250 stopped the therapy. After propensity score matching, the high-risk group comprised 348 patients (174 patients in each group). The extended therapy group had significantly higher 10-year DFS and distant DFS rates than did the stop group. The multivariate Cox model indicated a 69% reduction in recurrence risk for the extended therapy group. Conclusions Extended endocrine therapy significantly improves DFS in patients with high-risk ER-positive, HER2-negative breast cancer, especially in those with large tumors, lymph node involvement, and high tumor grade. These findings support personalized treatment strategies for enhancing long-term outcomes.