Systemic or Vaginal Hormone Therapy After Early Breast Cancer: A Danish Observational Cohort Study

Abstract

Background Women treated for breast cancer (BC) often suffer genitourinary syndrome of menopause. These symptoms may be alleviated by vaginal estrogen therapy (VET) or menopausal hormone therapy (MHT). However, there are concerns of risks of recurrence of BC and death following treatment. Methods Our study included longitudinal data from a national cohort of postmenopausal women, diagnosed 1997-2004 with early-stage invasive estrogen receptor–positive nonmetastatic BC, who received no treatment or 5 years of adjuvant endocrine therapy. We ascertained prescription data on hormone therapy, VET or MHT, from a national prescription registry. We evaluated mortality and risk of recurrence associated with use of VET and MHT vs non-use using multivariable models adjusted for potential confounders. Results Among 8461 women who had not received VET or MHT before BC diagnosis, 1957 and 133 used VET and MHT, respectively, after diagnosis. 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 to 1.32) for VET (1.39 [95% CI = 1.04 to 1.85 in the subgroup receiving adjuvant aromatase inhibitors]) and 1.05 (95% CI = 0.62 to 1.78) for MHT. The adjusted hazard ratios for overall mortality were 0.78 (95% CI = 0.71 to 0.87) and 0.94 (95% CI = 0.70 to 1.26) for VET and MHT, respectively. Conclusions In postmenopausal women treated for early-stage estrogen receptor–positive BC, neither VET nor MHT was associated with increased risk of recurrence or mortality. A subgroup analysis revealed an increased risk of recurrence, but not mortality, in patients receiving VET with adjuvant aromatase inhibitors.

Safety of Vaginal Estrogen Therapy for Genitourinary Syndrome of Menopause in Women With a History of Breast Cancer

“…20 A recent Danish cohort study of 8,461 women described no increased risk of recurrence or mortality in postmenopausal women with a history of early-stage breast cancer after treatment with vaginal estrogen therapy or menopausal hormone therapy. 13 Similar to the Danish study, we observed a significantly increased risk of breast cancer recurrence among those with concurrent vaginal estrogen and aromatase inhibitor prescriptions. 13 It is possible that this increased risk may be multifactorial, including the characteristic of breast cancer, the dosage of vaginal estrogen and aromatase inhibitors, and the temporal relationship of breast cancer diagnosis to vaginal estrogen therapy initiation for genitourinary syndrome of menopause, but data are limited.…”

“…13 Similar to the Danish study, we observed a significantly increased risk of breast cancer recurrence among those with concurrent vaginal estrogen and aromatase inhibitor prescriptions. 13 It is possible that this increased risk may be multifactorial, including the characteristic of breast cancer, the dosage of vaginal estrogen and aromatase inhibitors, and the temporal relationship of breast cancer diagnosis to vaginal estrogen therapy initiation for genitourinary syndrome of menopause, but data are limited. It is important to note that we did not observe an increased risk of breast cancer recurrence when controlling for total number of individual anastrozole, letrozole, and exemestane prescriptions between the cohorts; the risk was seen only with concurrent prescriptions, although our study was likely underpowered to detect those risk differences.…”

“…Consistent with previous studies, an increased risk of breast cancer recurrence was seen with concurrent aromatase inhibitor and vaginal estrogen use, with the greatest risk in the first year after therapy initiation for genitourinary syndrome of menopause diagnosis. 13 As seen in other studies, our results suggest that vaginal estrogen may be underprescribed in this population, with only about 5% of patients receiving three or more vaginal estrogen prescriptions. 7 Furthermore, only 4% of patients with a history of estrogen receptor–positive breast cancer received vaginal estrogen after a genitourinary syndrome of menopause diagnosis.…”

Therapeutic Choices for Genitourinary Syndrome of Menopause (GSM) in Breast Cancer Survivors: A Systematic Review and Update

“…The authors concluded that in postmenopausal BCS, neither VET nor MHT was associated with an increased risk of recurrence or mortality. A subgroup analysis revealed an increased risk of recurrence, but not mortality, in patients receiving VET with adjuvant aromatase inhibitors [52].…”

A systematic review of randomised clinical trials – The safety of vaginal hormones and selective estrogen receptor modulators for the treatment of genitourinary menopausal symptoms in breast cancer survivors

“…14 Studies determining this risk of cancer recurrence following vaginal estrogen therapy amongst breast cancer survivors however remain conflicting. 15,16…”