Abstract PS3-08-30: Evaluation of Late Recurrence Risk in Premenopausal N0-N1 Breast Cancer Using the CTS5 Score

Abstract Background: Estrogen receptor (ER)-positive, HER2-negative breast cancer has a prolonged risk of recurrence extending up to 20 years after surgery. Extended endocrine therapy can reduce late recurrence; however, optimal selection and treatment duration remain unclear. The Clinical Treatment Score post-5 years (CTS5) is a simple tool using clinicopathological factors to estimate late recurrence risk, and this score stratifies late recurrence risk into low (<3.13), intermediate (3.13-3.86), and high (>3.86) groups. Although validated primarily in postmenopausal patients, CTS5’s utility in premenopausal, N0-N1 patients has not been established. This study retrospectively assessed late recurrence risk by CTS5 and evaluated the impact of extended endocrine therapy in this lower-risk population. Methods: We analyzed ER-positive, HER2-negative, non-metastatic breast cancer patients with pathological N0-1 disease treated with curative surgery between 2003-2017, excluding those with early recurrence or insufficient follow-up. CTS5 scores were calculated and categorized into risk groups, and the duration of endocrine therapy was classified as standard (7 years) or extended (≥7 years). Distant recurrence-free survival was assessed using Kaplan-Meier and Cox regression analyses to identify prognostic factors. Results: A total of 879 patients were included in this study. Median age was 45 years; 75.9% had node-negative disease and 58.5% had pathologic stage I. Adjuvant chemotherapy was administered in 30.3%, and ovarian function suppression in 27.3%. SERM was used in 76.7% of patients. The mean CTS5 score was 2.73, with 70.3% low-risk, 22.4% intermediate, and 7.1% high risk. Extended endocrine therapy ≥7 years was given to 37.7% of patients.Over a median follow-up of 8.9 years, 31 distant recurrences occurred. Eight-year distant recurrence-free survival was 99.1% (95% CI 98.2-99.9) in the low-risk group, 95.5% (92.3-98.9) in the intermediate, and 93.7% (87.1-100.0) in the high CTS5 groups (log-rank p<0.001). In multivariable analysis adjusting for age, adjuvant chemotherapy, ovarian suppression, and extended endocrine therapy, intermediate (HR 4.73, 95% CI 2.02—11.05, p<0.001) and high CTS5 groups (HR 5.44, 95% CI 1.29-22.92, p=0.021) were significantly associated with increased risk of distant recurrence. Extended endocrine therapy ≥7 years was associated with a trend toward reduced recurrence risk (HR 0.14, 95% CI 0.02-1.09, p=0.06). Conclusion: In this premenopausal N0-N1 cohort, CTS5 effectively stratified late recurrence risk despite the generally lower-risk population. While patients with intermediate or high CTS5 scores had significantly higher recurrence and are likely to benefit from extended endocrine therapy, patients in the low-risk group may avoid prolonged treatment, potentially sparing adverse effects and preserving quality of life. Citation Format: A. Saito, T. Shimoi, T. Murata, M. Onshi, M. Yoshida, A. Ogawa, A. Nakashoji, H. Maeda, C. Watase, S. Takayama, K. Yonemori. Evaluation of Late Recurrence Risk in Premenopausal N0-N1 Breast Cancer Using the CTS5 Score [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-08-30.