Patterns, Predictors, and Prognostic Implication of Treatment-Related Amenorrhea in Patients with Breast Cancer: A retrospective study

Background: Treatment-related amenorrhea (TRA) is a common consequence of systemic therapy in premenopausal women with breast cancer and may affect fertility, quality of life, and reproductive health. However, predictors of persistent TRA and its prognostic relevance remain uncertain. Material and Methods: A retrospective observational study of 200 premenopausal women with histologically confirmed breast cancer treated with systemic therapy at a tertiary cancer centre. Clinical, pathological, and treatment-related variables were extracted from medical records. TRA was assessed longitudinally, with persistent TRA defined as treatment-associated amenorrhea lasting ≥12 consecutive months without documented spontaneous menstrual recovery. Logistic regression was used to identify predictors of TRA and persistent TRA. Disease-free survival (DFS) and overall survival (OS) were evaluated using Cox proportional-hazards models. Results: TRA occurred in 124 (62.0%) patients, including 78 (39.0%) with persistent and 46 (23.0%) with transient TRA. Age ≥40 years was independently associated with TRA (adjusted OR [aOR], 2.82; 95% CI, 1.49–5.34; P=0.002) and persistent TRA (aOR, 3.48; 95% CI, 1.58–7.67; P=0.002). Alkylating-agent exposure independently predicted TRA (aOR, 2.21; 95% CI, 1.07–4.58; P=0.033), while ovarian function suppression was associated with both TRA (aOR, 2.34; 95% CI, 1.06–5.17; P=0.035) and persistent TRA (aOR, 2.71; 95% CI, 1.13–6.51; P=0.026). TRA was not significantly associated with DFS (adjusted HR, 0.71; 95% CI, 0.37–1.36; P=0.304) or OS (adjusted HR, 0.61; 95% CI, 0.25–1.49; P=0.278). Conclusion: TRA is common among premenopausal women receiving breast cancer therapy. Older age is the strongest predictor of persistent amenorrhea, while treatment-related ovarian suppression contributes substantially to menstrual dysfunction. TRA was not independently prognostic for DFS or OS.

Keywords: Breast cancer, treatment-related amenorrhea, chemotherapy-induced amenorrhea, ovarian function, ovarian function suppression, menstrual recovery, fertility preservation, premenopausal women.