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.