Is Breast Cancer Risk Associated with Menopausal Hormone Therapy Modified by Current or Early Adulthood BMI or Age of First Pregnancy?

SIMPLE SUMMARY: Menopausal hormone therapy (MHT) increases risk of developing breast cancer (BC), and women are often advised to avoid its use for this reason. In this analysis we examined the size of this effect using data from a large cohort of women attending breast cancer screening in Manchester, UK. We additionally explored the extent to which risk from MHT might be modified by current BMI, early adulthood body mass index (BMI) (age 20 years), and age of first pregnancy. Identifying modifying effects would help enable better estimation of risk associated with MHT for an individual woman. Results indicated that women using combined oestrogen and progestagen MHT were at greater risk than those receiving oestrogen-only MHT. The Relative risk associated with MHT was less for obese women than non-obese women. After adjustment for current BMI, the effect of MHT did not appear to be substantially modified by early BMI or age of pregnancy. ABSTRACT: Menopausal hormone therapy (MHT) has an attenuated effect on breast cancer (BC) risk amongst heavier women, but there are few data on a potential interaction with early adulthood body mass index (at age 20 years) and age of first pregnancy. We studied 56,489 women recruited to the PROCAS (Predicting Risk of Cancer at Screening) study in Manchester UK, 2009-15. Cox regression models estimated the effect of reported MHT use at entry on breast cancer (BC) risk, and potential interactions with a. self-reported current body mass index (BMI), b. BMI aged 20 and c. First pregnancy >30 years or nulliparity compared with first pregnancy <30 years. Analysis was adjusted for age, height, family history, age of menarche and menopause, menopausal status, oophorectomy, ethnicity, self-reported exercise and alcohol. With median follow up of 8 years, 1663 breast cancers occurred. BC risk was elevated amongst current users of combined MHT compared to never users (Hazard ratioHR 1.64, 95% CI 1.32–2.03), risk was higher than for oestrogen only users (HR 1.03, 95% CI 0.79–1.34). Risk of current MHT was attenuated by current BMI (interaction HR 0.80, 95% CI 0.65–0.99) per 5 unit increase in BMI. There was little evidence of an interaction between MHT use, breast cancer risk and early and current BMI or with age of first pregnancy.