Estrogen, The Double-Edged Sword In Breast Cancer—A Systematic Review

Background: Estrogen is a crucial hormone in female physiology but plays a paradoxical role in the pathogenesis of breast cancer. While it promotes the proliferation of estrogen receptor–positive tumor cells under specific biological conditions, it may also induce apoptosis and hinder tumour progression-a "double-edged sword." Objectives:The purpose of this systematic review is to determine whether estrogen plays a dual role in breast cancer, examining the tumour-promoting and tumour-suppressive mechanisms of estrogen, as well as discussing the clinical implications of these features regarding HRT and endocrine treatment strategies. Methods: The literature was comprehensively reviewed by searching the databases PubMed, ResearchGate, and ScienceDirect, as well as leading oncology journals, using keywords such as “estrogen,” “breast cancer,” “hormone replacement therapy,” and “postmenopausal women.” Searches were limited to randomised control trials, cohort studies, and observational studies that were published between 2000 and 2018. Five eligible full-text studies were included in the analysis. Results: The findings showed that the influence of estrogen was dependent on time, dose, and hormone context. Combined estrogen–progestin increased breast cancer risk, while long-term estrogen-only therapy had neutral or mildly protective effects in postmenopausal women. Gene-expression assays such as the Breast Cancer Index and Endo Predict enhanced recurrence risk stratification, separating patients who may benefit from prolonged endocrine therapy from those who could safely stop. Conclusion: Estrogen carries both oncogenic and therapeutic properties in breast cancer, and its biological and temporal context lies at the heart of this duality. Understanding this is imperative for optimising endocrine therapy, individualising duration of treatment, and minimising risk. Elucidation of molecular mechanisms and validation of prognostic tools in diverse patient populations could refine clinical decisionmaking in estrogen-related management of breast cancer