Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort

Agnès Fournier, Sylvie Mesrine, Laure Dossus, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Nathalie Chabbert-Buffet

Questions remain on how the excess risk of breast cancer associated with menopausal hormone therapy (MHT) evolves after treatment stops. We investigated that issue in the E3N cohort, with 3,678 invasive breast cancers identified between 1992 and 2008 among 78,353 women (881,290 person-years of postmenopausal follow-up). Exposure to MHT was assessed through biennial self-administered questionnaires and classified by type of progestagen component (progesterone or dydrogesterone; other progestagen), duration (short-term ≤5 years; long-term >5 years) and time since last use (current, 3 months-5 years, 5-10 years, 10+ years). Hazard ratios (HR) and confidence intervals (CI) were estimated with Cox models. Among short-term users, only those currently using estrogens associated with a progestagen other than progesterone/dydrogesterone had a significantly elevated breast cancer risk (HR 1.70, 95 % CI 1.50-1.91, compared with never users). Long-term use of this type of MHT was associated with a HR of 2.02 (1.81-2.26) when current and of 1.36 (1.13-1.64), 1.34 (1.04-1.73), and 1.52 (0.87-2.63) when stopped ≤5, 5-10, and 10+ years earlier, respectively. Our results suggest residual increases in breast cancer risk several years after MHT cessation, which are restricted to long-term treatments. Whether increases persist more than 10 years after cessation deserves continuing investigation.