Reassessing Safety of Vaginal Estrogen in Women with Breast Cancer

Women with breast cancer prescribed adjuvant endocrine therapy often experience side effects such as arthralgias, hot flashes, urinary symptoms, and vaginal symptoms including dryness and dyspareunia. Because adjuvant therapy is prescribed for 5 years or more, compliance and adherence are major issues, and these side effects often contribute to discontinuation. Efforts to mitigate side effects are important, but use of hormones to offset them raises concern about possible increased risk of breast cancer recurrence.

Using a national prescription database and the Danish Breast Cancer Group clinical database, investigators evaluated the use of vaginal estrogen therapy (VET) and menopausal hormone therapy (MHT) in a cohort of postmenopausal women diagnosed with early-stage, hormone receptor–positive breast cancer from 1997 to 2004 who received either 5 years of adjuvant endocrine therapy or no such therapy.

A total of 8461 patients were identified who had not received VET or MHT prior to diagnosis, and of these, 1957 used VET and 133 used MHT after diagnosis. Users were defined as those who filled at least two prescriptions after diagnosis. Median patient age was 61 years, 77% had invasive ductal carcinoma, and 57% were node negative.

Adherence to adjuvant endocrine therapy was 88% in users of VET and 90% in never-users. Median follow-up was nearly 10 years for recurrence and 15 years for overall survival. Use of VET or MHT was not associated with an increased risk for either recurrence or mortality in the overall population. However, there was an increased risk for recurrence in the subgroup of patients (n=822) receiving VET with adjuvant aromatase inhibitors (adjusted hazard ratio, 1.39); no increased risk was observed among women taking tamoxifen.