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Are Vaginal Estrogen and Menopausal Hormonal Therapies Linked to an Increased Risk of Breast Cancer Recurrence?

By: Anna Fanelli
Posted: Tuesday, September 6, 2022

Patients treated for early-stage estrogen receptor–positive breast cancer may experience genitourinary syndrome of menopause. The symptoms of this syndrome are often treated with vaginal estrogen therapy or menopausal hormone therapy. Given the concerns regarding the risks of breast cancer recurrence and death following these treatments, Søren Cold, MD, of Odense University Hospital, Denmark, and colleagues conducted an observational cohort study. The findings of this study, which were reported in the Journal of the National Cancer Institute, suggested that neither of these therapies was associated with an increased risk of recurrence or mortality. However, a subgroup analysis showed an increased risk of recurrence—but not mortality—in those who received adjuvant aromatase inhibitors.

“This large cohort study helps to inform the nuanced discussions between clinicians and breast cancer survivors about the safety of vaginal estrogen therapy,” said Elizabeth J. Cathcart-Rake, MD, of the Mayo Clinic, Rochester, Minnesota, who coauthored an editorial to accompany this article in the Journal of the National Cancer Institute.

In this trial, the authors included data from a national cohort of postmenopausal women with early-stage invasive estrogen receptor–positive nonmetastatic breast cancer. Among 8,461 women who had not received vaginal estrogen therapy or menopausal hormone therapy before their breast cancer diagnosis, 1,957 and 133 patients used vaginal estrogen therapy and menopausal hormone therapy after diagnosis. The median follow-up was 9.8 years for recurrence and 15.2 years for mortality.

The adjusted relative risk of recurrence was 1.08 (95% confidence interval [CI] = 0.89–1.32) for vaginal estrogen therapy and 1.05 (95% CI = 0.62–1.78) for menopausal hormone therapy. The adjusted relative risk of recurrence in the subgroup receiving adjuvant aromatase inhibitors was 1.39 (95% CI = 1.04–1.85) with vaginal estrogen therapy. As for the adjusted hazard ratios for overall mortality, they were 0.78 (95% CI = 0.71–0.87) and 0.94 (95% CI = 0.70–1.26) with vaginal estrogen and menopausal hormone therapies, respectively.

Disclosure: For full disclosures of the study authors, visit

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