Abstract Background: Breast cancer is the most commonly diagnosed tumor in women. Women with de novo metastatic breast cancer (dnMBC), as a heterogeneous group, especially in young patients, represent a peculiar population with respect to tumor biology, prognosis, clinical management and survivorship issues. Currently, systemic chemotherapy remains the cornerstone of treatment for this disease. Chemotherapy-related amenorrhea (CRA) is a common complication observed in premenopausal women with breast cancer, and the incidence of CRA ranges from 15% to 94% in patients with breast cancer after receiving chemotherapy. However, up to now, its role in dnMBC remains unknown. Aim: To to investigate the clinical risk factors associated with CRA and to assess its impact on the prognosis of premenopausal women with dnMBC. Settings and design: This study was designed as a retrospective cohort study and was approved by the Ethics Committee of Hebei Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine (NO. 2017-AF29-058). Methods: Using hospital-based database, we identified women with dnMBC diagnosed between March 2010 and December 2017, collected demographic data, tumor characteristics, histopathological reports, treatment types and courses (including records of chemotherapy response and menstrual effects), and survival data. A retrospective analysis was conducted on the associated factors and prognostic effects of CRA in 291 out of 518 premenopausal patients who received continuous adjuvant chemotherapy (ACT regimen) or chemotherapy with AC regimen. Premenopausal status was defined as last normal menses within the 6 weeks preceding initiation of chemotherapy; CRA as cessation of menses for at least 3 months not later than 3 months from the end of chemotherapy. The primary outcome was overall survival (OS). It was estimated by Kaplan-Meier method and log rank test. Univariable and multivariable analyses were performed using the COX proportional hazard model to identify statistically significant prognostic factors. All statistical analyses were performed using Stata 18.0. Results: A total of 291 premenopausal patients with de novo metastatic breast cancer were included in this study. The mean patient age was 45.1 years (SD 7.8). 29.1% of the patients are over 50 years old, and there are 10 patients who are 56 years old. The majority of the patients had histopathological diagnoses of invasive ductal carcinoma (96.7%). The mean age of patients was higher for patients who had clinical amenorrhea compared to those who did not have it: 48.7 (SD 5.1) vs. 36.9 (SD 6.7) years, with a significant statistical difference (Diff:-11.7;95%CI -13.3 to -10.1;p0.001]). Compared with women who had not experienced amenorrhea, the OS of patients with CRA was longer, with a significant statistical difference (hazard ratios: 0.68; 95% CI0.51-0.90;p=0.006). The prognostic value of CRA was independent of age, hormone receptor status, chemotherapy regimen, and chemotherapy cycles. Conclusions: This cohort study indicates that in premenopausal women with dnMBC, the condition of CRA is common, and it has a favorable prognosis compared to patients without amenorrhea. Further large cohort studies are necessary to confirm these results. Citation Format: C. Ren, J. Sun, L. Kong, H. Yu, F. Wang, H. Qi. Prognostic significance of chemotherapy-related amenorrhea in premenopausal women with de novo metastatic breast cancer 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 PS1-09-09.
Ren et al. (Tue,) studied this question.