Menopausal hormone therapy and breast cancer risk: effect modification by body mass through life

Abstract

It is not known whether increased breast cancer risk caused by menopausal hormone therapy (HT) depends on body mass patterns through life. In a prospective study of 483,241 Norwegian women aged 50-69 years at baseline, 7656 women developed breast cancer during follow-up (2006-2013). We combined baseline information on recalled body mass in childhood/adolescence and current (baseline) body mass index (BMI) to construct mutually exclusive life-course body mass patterns. We assessed associations of current HT use with breast cancer risk according to baseline BMI and life-course patterns of body mass, and estimated relative excess risk due to interaction (RERI). Within all levels of baseline BMI, HT use was associated with increased risk. Considering life-course body mass patterns as a single exposure, we used women who "remained at normal weight" through life as the reference, and found that being "overweight as young" was associated with lower risk (hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.76-0.94), whereas women who "gained weight" had higher risk (HR 1.20, 95% CI 1.12-1.28). Compared to never users of HT who were "overweight as young", HT users who either "remained at normal weight" or "gained weight" in adulthood were at higher risk than expected when adding the separate risks (RERI 0.52, 95% CI 0.09-0.95, and RERI 0.37, 95% CI - 0.07-0.80), suggesting effect modification. Thus, we found that women who remain at normal weight or gain weight in adulthood may be more susceptible to the risk increasing effect of HT compared to women who were overweight as young.

Can breast cancer be stopped? Modifiable risk factors of breast cancer among women with a prior benign or premalignant lesion

“…31 Overweight after menopause is associated with increased risk of breast cancer, while overweight before menopause decreases risk. 18 In our study, exclusion of self-reported premenopausal women did not change our results. Women with dense breasts and atypia or a carcinoma in situ lesion may be of higher risk of subsequent breast cancer.…”

“…44 Self-reported HT use in BreastScreen Norway correspond well to dispensed prescription data. 18 Nonsystematic measurement errors in the covariates are associated with effect estimates biased toward a null result.…”

“…The associations between known risk factors and breast cancer among women participating in the population-based mammographic screening program BreastScreen Norway have been reported in several articles. [13][14][15][16][17][18][19] Participants with a false-positive screening examination and those diagnosed with a premalignant lesion had an increased long-term risk of invasive breast cancer compared to women screened negative (2-fold relative risk after additional imaging or a biopsy with benign results, 3-fold after detection of hyperplasia with atypia, 4-fold after a carcinoma in situ diagnosis). 20 Genetic and environmental risk factors for carcinoma in situ are similar to those for invasive breast cancer.…”

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

“…The study reported that current users of MHT who reported being overweight at the ages of 7 and 15 (self-identified as being heavier than their peers) were at higher risk (HR 1.68, 95% CI 1.32–2.14) compared to never users of MHT who were overweight as young. However, risks were higher amongst current MHT users who remained at normal weight throughout adult life (HR 2.25, 95% CI 1.93–2.62) or who had gained weight (HR 2.28, 95% CI 1.94–2.67) [ 35 ]. The authors reported these risks were higher than expected when adding the separate risks of BMI and MHT with respective relative excess risk due to the interaction scores of 0.52 (95% CI 0.09–0.95) and 0.37 (95% CI -0.07 – +0.08).…”

Validating Breast Cancer Risk Prediction Models in the Korean Cancer Prevention Study-II Biobank

“…Model fit might also be improved by tailoring categories for available data to the Korean population, for example, using Asian-specific WHO cutoffs for overweight and obesity (41). The relative risk models also do not include interactions among the risk factors, for example between body mass index and hormone therapy (9,(42)(43)(44). Further research should consider more comprehensive models including history of breastfeeding and other risk factors, such as breast density, bone mineral density, and genetic and biomarkers.…”