Differential prognostic impact of clinicopathologic factors for late recurrence in ER-positive breast cancer according to menopausal status

초록

Purpose: Identifying high-risk patients for late recurrence is crucial for optimizing extended endocrine therapy (EET). This study investigated how clinicopathologic predictors of late recurrence diverge according to menopausal status in estrogen receptor (ER)-positive breast cancer patients who completed 5-year endocrine therapy. Methods: We retrospectively analyzed 1549 patients with stage I-III ER-positive breast cancer who completed 5 years of endocrine therapy and remained recurrence-free during that period. Median follow-up was 14.7 years. Outcomes included distant metastasis-free survival (DMFS) and overall survival (OS). Analyses were stratified by menopausal status to identify status-specific risk factors. Results: During the follow-up period, 208 patients (13.4 %) experienced late recurrence, with distant metastasis (6.3 %) being the most frequent event. Kaplan-Meier analyses demonstrated that tumor size >2 cm and higher nodal stage were significantly associated with inferior DMFS and OS in both subgroups (all P < .05). However, multivariable analysis revealed distinct prognostic patterns according to menopausal status. In premenopausal women, nodal involvement was the most potent driver of late recurrence; N1 stage significantly increased the risk of poor DMFS (HR 3.14, 95 % CI 1.54-6.40; P = .002) and OS (HR 3.39, 95 % CI 1.45-7.93; P = .005). Furthermore, age at diagnosis showed a significant inverse association with distant metastasis risk, with each one-year decrease in age increasing the risk by 6 % (HR 0.94; P = .019). In contrast, for postmenopausal patients, tumor size (>2 cm) emerged as the predominant predictor for both DMFS (HR 2.70; P = .006) and OS (HR 2.26; P = .039), whereas the prognostic impact of nodal stage was notably diminished (N1: P = .374 for DMFS; P = .999 for OS). In this group, older age was independently associated with worse OS (HR 1.13; P < .001) but did not significantly impact DMFS. Conclusion: Predictors for late recurrence are different depending on menopausal status: nodal burden and young age dominate in premenopausal patients, whereas tumor size is more critical in postmenopausal patients. These findings suggest that menopausal status must be a primary consideration in risk-stratification models for EET and long-term surveillance.

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