Does Suppressing Ovarian Estrogen Production Provide Additional Benefit in Young Patients at High Risk of Breast Cancer Recurrence?

According to research newly published in the British medical journal NEJM, suppressing ovarian estrogen production in addition to hormonal treatment after surgery and chemotherapy reduced recurrence risk in a group of breast cancer patients.

Some cancer cells need estrogen to grow. Such breast cancers are called hormone receptor-positive. Hormonal treatment after surgery and chemotherapy has long been fundamental in early-stage hormone receptor-positive breast cancer. Tamoxifen blocks estrogen receptors in breast tissue, thereby preventing cancer spread. Until now, standard treatment in premenopausal women was tamoxifen, which reduced recurrence likelihood by %20-30. Other hormone-suppressing drugs are aromatase inhibitors (anastrozole, letrozole, exemestane), which are not used before menopause. Aromatase is an enzyme enabling estrogen synthesis, and aromatase inhibitors suppress it in fat tissue to prevent estrogen production. Using hormone-suppressing drugs other than tamoxifen before menopause is inappropriate because aromatase inhibitors can increase estrogen when ovarian function remains intact, producing the opposite effect. Premenopausal use is possible only with drugs that stop ovarian function.

Clinical trials to date have not comprehensively compared tamoxifen alone, tamoxifen with ovarian suppression, and aromatase inhibitors with ovarian suppression. This NEJM article compared treatments in premenopausal women: tamoxifen alone, tamoxifen with ovarian suppression, and an aromatase inhibitor (exemestane in this study) with ovarian suppression, forming 3 arms. Ovarian suppression produced a borderline benefit in the group at high risk of breast cancer recurrence.

We currently use tamoxifen with ovarian-suppressing drugs for 2-3 years in high-risk young women. This new study supports their use in this group. However, it provides no direct conclusion about combining aromatase inhibitors with ovarian-suppressing drugs.