CLINICAL QUESTION

Is the use of vaginal estrogen in breast cancer survivors associated with increased recurrence or mortality?

BOTTOM LINE

The meta-analysis of observational studies of female breast cancer survivors showed no increase in the incidence of breast cancer recurrence, breast cancer–specific mortality, or overall mortality with the use of topical vaginal estrogen compared with nonuse. The use of topical vaginal estrogen was associated with better outcomes for breast cancer recurrence and overall mortality. Caution should be used in interpreting these results because of a potential healthy volunteer effect among estrogen users. (Level of Evidence = 2a−)

SYNOPSIS

The authors conducted a systematic review and meta-analysis of eight observational studies that compared outcomes with and without the use of vaginal estrogen in female breast cancer survivors. They assessed outcomes of breast cancer recurrence (local, contralateral breast, or metastasis), breast cancer–specific mortality, and all-cause mortality. The authors were unable to identify any randomized controlled trials on this topic. Included studies showed low risk of bias and were heterogeneous based on differences in regimens and duration. They excluded studies that used systemic hormone regimens. There were too few studies to assess publication bias. They found that there was no association with increased incidence for any of the outcomes in breast cancer survivors who used topical vaginal estrogen: recurrence (520 in 4,494 [11.6%] users vs 3,086 in 19,566 [15.8%] nonusers; odds ratio = 0.48; 95% CI, 0.23–0.98; P = .04), breast cancer–specific mortality (23.4% vs 11.8%), and all-cause mortality (17.2% vs 23.4%). The authors caution that women who used topical estrogen were likely healthier overall, which can make their outcomes more favorable—the heathy volunteer effect seen in early observational studies of hormone therapy.