The Prospective Association between Early Life Growth and Breast Density in Young Adult Women

Simple Summary Breast cancer is the most common cancer worldwide and a leading cause of cancer-related deaths in women. Mammographic breast density, the relative amount of fibroglandular tissue as seen on a mammogram, is one of the strongest predictors of breast cancer risk, with higher breast density associated with greater risk. Breasts undergo extensive fibroglandular tissue proliferation in early life, making this a potential window of vulnerability for carcinogen exposures. Early-life growth (e.g., height and weight) is also associated with breast cancer risk. Research into the 'developmental origins of health and disease' paradigms investigate the pathways of risk for disease in later life from early-life exposures across developmental phases. However, little is known about the association between early-life growth and breast density. Further investigation into these risk pathways could increase knowledge of disease etiology and help identify women at increased risk at an earlier age and inform potential mediation of breast cancer risk.Abstract Breast density is a strong intermediate endpoint to investigate the association between early-life exposures and breast cancer risk. This study investigates the association between early-life growth and breast density in young adult women measured using Optical Breast Spectroscopy (OBS) and Dual X-ray Absorptiometry (DXA). OBS measurements were obtained for 536 female Raine Cohort Study participants at ages 27-28, with 268 completing DXA measurements. Participants with three or more height and weight measurements from ages 8 to 22 were used to generate linear growth curves for height, weight and body mass index (BMI) using SITAR modelling. Three growth parameters (size, velocity and timing) were examined for association with breast density measures, adjusting for potential confounders. Women who reached their peak height rapidly (velocity) and later in adolescence (timing) had lower OBS-breast density. Overall, women who were taller (size) had higher OBS-breast density. For weight, women who grew quickly (velocity) and later in adolescence (timing) had higher absolute DXA-breast density. Overall, weight (size) was also inversely associated with absolute DXA-breast density, as was BMI. These findings provide new evidence that adolescent growth is associated with breast density measures in young adult women, suggesting potential mediation pathways for breast cancer risk in later life.