Fatal Breast Cancer Risk in Relation to Use of Unopposed Estrogen and Combined Hormone Therapy

Abstract

Purpose: Use of combined menopausal hormone therapy (CHT) is associated with an increased risk of developing breast cancer, but it remains unclear to what degree the increase in incidence translates into an increase in breast cancer mortality. We evaluated fatal breast cancer risk in relation to recency and duration of use of CHT and unopposed estrogen hormone therapy (EHT). Methods: We conducted a large population-based nested case-control study in the Canadian province of Saskatchewan, where a population-based prescription drug database has existed since 1975. Cases (n = 1,288) were women who died of breast cancer in Saskatchewan between 1990-2008 at 50-79 years of age, and were eligible for Saskatchewan Prescription Drug Plan benefits for at least 5 years prior to their first primary breast cancer diagnosis (index date). Controls (n = 12,535) were matched to cases on duration of eligibility for health benefits prior to the index date and year of birth. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. Results: Exclusive use of EHT was not associated with risk of fatal breast cancer, neither overall nor within categories of recency and duration of use (OR for current use versus never use = 1.05; 95% CI: 0.83-1.34). Use of CHT (includes women who had also used EHT) was also not associated with fatal breast cancer risk (OR for current use versus never use = 0.93; 95% CI: 0.67-1.28), except for a suggestion of an increased risk associated with current long-term use. However, the number of women in this category of use was small and the confidence intervals wide. Conclusions: Consistent with several other studies, we observed no association between fatal breast cancer risk and use of EHT. Only a few studies have evaluated the association between fatal breast cancer risk and use of CHT, and collectively the results have been inconsistent. It remains to be seen whether women who take CHT are at an increased risk of dying from breast cancer.