Associations of early life body size and pubertal timing with breast density and postmenopausal breast cancer risk: A mediation analysis

PURPOSE: Whether breast density mediates associations between early life body size and pubertal timing with postmenopausal breast cancer is underexplored.

METHODS: We studied 33,939 Danish women attending the Capital Mammography Screening Program at ages 50-69 years. Early life anthropometry and pubertal timing information came from the Copenhagen School Health Records Register. Postmenopausal breast cancer information came from the Danish Breast Cancer Group database (n = 833). Breast density (BI-RADS) was categorized as low (n = 25,464; 75 %) or high. Risk ratios (RR) and hazard ratios (HR) were estimated using generalized linear regression and Cox proportional hazards analyses. Counterfactual mediation analyses were conducted.

RESULTS: Evidence was limited for associations between birthweight and pubertal timing with breast density or breast cancer. Childhood BMI was inversely associated with high breast density (age 13y, RR=0.77 [0.72-0.81] for a z-score of 0.6 versus 0) and breast cancer (HR=0.90 [0.83-0.96] per z-score). Breast density mediated 37 % (17-170 %) of this association. Although childhood height was associated with breast density and breast cancer, there were few indications of mediation by breast density.

CONCLUSIONS: Breast density may partially explain the inverse association between childhood BMI and postmenopausal breast cancer, but not the positive association between childhood height and postmenopausal breast cancer.