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.

Figure 1.

Use of menopausal hormone therapy (MHT) or vaginal estrogen therapy (VET) in a cohort of Danish women treated for early-stage breast cancer (BC) according to adjuvant endocrine therapy. Use of MHT, VET, or no hormonal treatment (none) among patients with early-stage BC 1997-2004 according to use of adjuvant endocrine treatment.

Figure 2.

Cumulative incidence of recurrence of breast cancer according to use of menopausal hormone therapy (MHT) or vaginal estrogen therapy (VET). Cumulative incidence of breast cancer recurrence following treatment among patients with early-stage breast cancer 1997-2004 according to use of MHT, VET, or no hormonal treatment (none). Numbers indicate numbers at risk from baseline and after 2, 4, 6, 8, and 10 years; the numbers diminish as patients shift to another group, have an event, or are censored for other reason.

Figure 3.

Overall survival (OS) according to use of menopausal hormone therapy (MHT) or vaginal estrogen therapy (VET). OS among patients with early-stage breast cancer 1997-2004 according to use of MHT, VET, or no hormonal treatment (none). Numbers indicate numbers at risk from baseline and after 5, 10, and 15 years, the numbers diminish as patients shift to another group, have an event, or are censored for other reason.