Vaginal Estrogen Therapy Use and Survival in Females With Breast Cancer

Abstract

ImportanceGenitourinary syndrome of menopause can be treated with vaginal estrogen therapy. However, there are concerns about the safety of vaginal estrogen therapy in patients with breast cancer.ObjectiveTo determine whether the risk of breast cancer–specific mortality was higher in females with breast cancer who used vaginal estrogen therapy vs females with breast cancer who did not use hormone replacement therapy (HRT).Design, Setting, and ParticipantsThis cohort study analyzed 2 large cohorts, one each in Scotland and Wales, of females aged 40 to 79 years with newly diagnosed breast cancer. These population-based cohorts were identified from national cancer registry records from 2010 to 2017 in Scotland and from 2000 to 2016 in Wales and were followed up for breast cancer–specific mortality until 2020. Females were excluded if they had a previous cancer diagnosis (except nonmelanoma skin cancer). Data analysis was performed between August 2022 and August 2023.ExposureUse of vaginal estrogen therapy, including vaginal tablets and creams, was ascertained from pharmacy dispensing records of the Prescribing Information System for the Scotland cohort and from general practice prescription records for the Wales cohort.Main Outcomes and MeasuresThe primary outcome was time to breast cancer–specific mortality, which was obtained from national mortality records. Time-dependent Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for breast cancer–specific mortality, comparing vaginal estrogen therapy users with HRT nonusers and adjusting for confounders, including cancer stage and grade.ResultsThe 2 cohorts comprised 49 237 females with breast cancer (between 40 and 79 years of age) and 5795 breast cancer–specific deaths. Five percent of patients with breast cancer used vaginal estrogen therapy after breast cancer diagnosis. In vaginal estrogen therapy users compared with HRT nonusers, there was no evidence of a higher risk of breast cancer–specific mortality in the pooled fully adjusted model (HR, 0.77; 95% CI, 0.63-0.94).Conclusions and RelevanceResults of this study showed no evidence of increased early breast cancer–specific mortality in patients who used vaginal estrogen therapy compared with patients who did not use HRT. This finding may provide some reassurance to prescribing clinicians and support the guidelines suggesting that vaginal estrogen therapy can be considered in patients with breast cancer and genitourinary symptoms.

Safety of vaginal oestrogens for genitourinary symptoms in women with breast cancer

“…Another cohort study from the UK with 49,237 females with breast cancer and a median duration of follow up of eight years reported no evidence of higher breast cancer-specific mortality in those who used vaginal oestrogen therapy after breast cancer diagnosis (n=2551, 5%) compared with those who did not, including women taking aromatase inhibitors. 25 Similarly, a Swedish case-control study showed no increase in breast cancer-specific mortality in patients with breast cancer who used oestrogen concurrent with tamoxifen and aromatase inhibitors. 26 Although reassuring, neither study reported on breast cancer recurrences and the follow-up times were short to report on early breast cancer mortality.…”

Managing sexual health challenges in breast cancer survivors: A comprehensive review

“…More recently, a large cohort study has evaluated a total of 49,237 early BC patients, of which 5 % received VaHT and about 1 % received SyHT. In this study, the use of VaHT was not associated with an increased risk of BC-associated mortality (HR 0.57; 95 % CI 0-34-0.96), irrespective of the duration of the exposure or the dosage of estrogens contained in the preparations [ 45 ]. Thereby, the consideration of employing low-dose vaginal estrogens to alleviate GSM in early BC patients could be contemplated, particularly given their proven clinical benefits after unsuccessful non-hormonal strategies.…”

The association of breast cancer patients survival and prior menopausal hormone therapy in women with type 2 diabetes

“…Local MHT is used for vulvovaginal and genitourinary symptoms. Although not as potent as systemic MHT, it improves the quality of life in a substantial proportion of patients and may also be used also in patients with breast cancer history with certain limitations 7 , 8 .While increased breast cancer risk with menopausal hormone therapy (MHT) is well known 9 , there is some evidence of a reduction in overall mortality among MHT-users 10 . The association between prediagnostic MHT use and cancer-specific and all-cause mortality among breast cancer patients has been found to be favorable compared to non-MHT users in most cohort studies, although results have been variable 11 – 18 .…”