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

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.