Safety of vaginal estrogen in breast cancer survivors: Current evidence on systemic absorption and oncologic outcomes

Abstract

Vaginal estrogen is widely used to manage the genitourinary syndrome of menopause. However, its use by breast cancer survivors remains controversial, since some labeling indicates that it may increase the risk of recurrence, based on the known risks of systemic hormone therapy. This review synthesizes current evidence on breast cancer incidence and the use of vaginal estrogen in postmenopausal women, and its systemic absorption, as well as recurrence, mortality, and comparative data among vaginal estrogen formulations in breast cancer survivors, including those receiving aromatase inhibitors. Our findings show that vaginal estrogen results in minimal systemic absorption, and no demonstrated increase in the incidence of breast cancer, its recurrence, or mortality from breast cancer. In breast cancer survivors treated with aromatase inhibitors, vaginal estrogen has not been associated with increased mortality, although evidence on its effect on recurrence remains controversial and the issue warrants further investigation. The absence of head-to-head comparisons of different formulations of vaginal estrogen in breast cancer survivors emphasizes the need for comparative studies to guide individualized treatment strategies. Recent updates from the US Food and Drug Administration, which removed boxed warnings related to breast cancer and acknowledged that vaginal estrogens have a safety profile that is distinct from that of systemic hormone therapy, reinforce our findings and represent an important step toward evidence-based regulation. Building on these regulatory advances, the increasing diagnosis of breast cancer in younger women and the prolonged burden of genitourinary syndrome of menopause underscore the need to translate this evidence into clinical practice by strengthening clinical confidence and supporting individualized, patient-centered decision-making for breast cancer survivors.

Keywords: Breast cancer mortality; Breast cancer recurrence; Breast cancer survivors; Drug safety; Genitourinary syndrome of menopause; Vaginal estrogen therapy.