Local estrogen therapy and risk of breast cancer recurrence among hormone-treated patients: a nested case–control study

Abstract

Women with estrogen-positive breast cancers receive endocrine treatment such as tamoxifen and aromatase inhibitors (AI) for 5-10 years. An important side effect of these drugs is vaginal dryness for which local hormonal therapy (LHT) represents the most effective treatment but is theoretically contraindicated. This study aimed to assess whether the use of LHT increases the risk of breast cancer recurrence among women receiving endocrine treatment. We conducted a cohort study with nested case-control analysis using the United Kingdom General Practice Research Database (GPRD). The cohort included female patients at least 18 years of age, newly diagnosed with breast cancer who received at least one AI or tamoxifen prescription between January 1, 1998 and June 30, 2008. Cases, who were patients experiencing a breast cancer recurrence during follow-up, were each matched with up to 10 controls based on age, date of cohort entry, type of endocrine treatment received, and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RR), and 95 % confidence intervals. A total of 13,479 women were included in the study, of which 2,673 received AIs, 10,806 received tamoxifen, and 271 received LHT. Mean (SD) age at cohort entry was 63.7 (14.1) years, and mean follow-up was 3.5 (2.6) years. The crude recurrence rate 25.9 per 1,000 per year. Overall, the use of LHT was not associated with an increased risk of recurrence (RR: 0.78, 95 % CI 0.48-1.25) compared with non-use. In stratified analyses, LHT did not increase the risk of recurrence among tamoxifen-treated patients (RR: 0.83, 95 % CI 0.51-1.34), while the risk was not estimable among AI-treated patients since no patients receiving LHT experienced a recurrence. The use of LHT is not associated with an increase in breast cancer recurrence among women receiving a hormone therapy.

Vaginal estrogen use for genitourinary symptoms in women with a history of uterine, cervical, or ovarian carcinoma

“…Compared with previously published data for the general population, the overall incidence of adverse outcomes associated with vaginal estrogen use was low 13 14 17 34. Prior studies have not demonstrated that local vaginal estrogen increases the incidence of embolic events 13–19. Similarly, in this series, the incidence of deep venous thromboembolism and pulmonary embolism is low at 1.6%.…”

“…In the general population, vaginal estrogen has been proven safe and efficacious 15 17. Furthermore, in women with breast cancer, including estrogen receptor-positive tumors, vaginal estrogen use does not increase risk of recurrence 18 19. To date, use of vaginal estrogen in women with a history of gynecologic cancer has not been studied.…”

Vaginal estrogen deficiency

“…Data regarding the safety of vaginal estrogen therapy in breast cancer survivors are limited. A case–control study of 271 women with breast cancer on tamoxifen or aromatase inhibitors concluded that there is no increased risk of recurrence in women on vaginal estrogen therapy, with a mean follow‐up of 3.5 years . In a retrospective cohort study, 60 women with early‐stage breast cancer were treated with an estradiol tablet or estriol cream for a median of 1 year.…”

Survivorship, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

“…128 However, evidence suggests that local estrogen does not increase the risk of breast cancer recurrence. 129 Vaginal estrogen preparations include rings, suppositories, and creams, and they have been shown to be effective for managing symptoms of vaginal dryness in menopausal women. 127,130 Limited data in breast cancer survivors suggest minimal systemic absorption with rings and suppositories and are therefore preferred for survivors with hormone-sensitive tumors if estrogen-based treatment is warranted.…”