Ovarian Function Suppression in Premenopausal Hormone Receptor-Positive Early Breast Cancer: A Comprehensive Review.

Abstract

Hormone receptor-positive (HR+) breast cancer in premenopausal women presents unique therapeutic challenges owing to persistent ovarian estrogen production and aggressive biological features. Although tamoxifen has long been the standard of care, the integration of ovarian function suppression (OFS) has transformed adjuvant management. This review synthesizes landmark clinical trial data, biological rationales, and emerging evidence to guide personalized treatment strategies. The hypothalamic-pituitary-ovarian axis remains the primary source of estrogen in premenopausal women and drives tumor proliferation. Landmark trials, including Suppression of Ovarian Function Trial, Tamoxifen and Exemestane Trial, Addition of Ovarian Suppression to Tamoxifen in Young Women with Hormone-Sensitive Breast Cancer who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy, and Hormonal Bone Effects, have established the superiority of OFS combined with aromatase inhibitors or tamoxifen over tamoxifen monotherapy in high-risk populations. However, the benefits must be weighed against toxicities such as bone loss, menopausal symptoms, and sexual dysfunction. Special subgroups, including young women, patients with invasive lobular carcinoma, and BRCA mutation carriers, derive distinct benefits from OFS. The phenomenon of ovarian escape and the potential of OFS to facilitate chemotherapy de-escalation are emerging as critical considerations. Suppression of ovarian function is the cornerstone of adjuvant therapy for high-risk premenopausal HR+ breast cancers. Optimal management requires a nuanced, risk-stratified approach that balances oncologic efficacy with long-term survivorship, integrating genomic tools and individualized duration strategies.