Growth Trajectories, Breast Size, and Breast-Tissue Composition in a British Prebirth Cohort of Young Women

Abstract

Mammographic percent density, the proportion of fibroglandular tissue in the breast, is a strong risk factor for breast cancer, but its determinants in young women are unknown. We examined associations of magnetic resonance imaging (MRI) breast-tissue composition at age 21 years with prospectively collected measurements of body size and composition from birth to early adulthood and markers of puberty (all standardized) in a sample of 500 nulliparous women from a prebirth cohort of children born in Avon, United Kingdom, in 1991-1992 and followed up to 2011-2014. Linear models were fitted to estimate relative change in MRI percent water, which is equivalent to mammographic percent density, associated with a 1-standard-deviation increase in the exposure of interest. In mutually adjusted analyses, MRI percent water was positively associated with birth weight (relative change (RC) = 1.03, 95% confidence interval (CI): 1.00, 1.06) and pubertal height growth (RC = 1.07, 95% CI: 1.02, 1.13) but inversely associated with pubertal weight growth (RC = 0.86, 95% CI: 0.84, 0.89) and changes in dual-energy x-ray absorptiometry percent body fat mass (e.g., for change between ages 11 years and 13.5 years, RC = 0.96, 95% CI: 0.93, 0.99). Ages at thelarche and menarche were positively associated with MRI percent water, but these associations did not persist upon adjustment for height and weight growth. These findings support the hypothesis that growth trajectories influence breast-tissue composition in young women, whereas puberty plays no independent role.

Circulating Growth and Sex Hormone Levels and Breast Tissue Composition in Young Nulliparous Women

“…A positive GH-percent-water association was reported by another study on the determinants of MRI breast tissue composition in young women (16) although, in contrast to our study, it found no evidence of an association with IGF-I. Our findings are also consistent with previously reported positive associations of childhood growth and adult height with breast cancer risk (36) and breast density, as ascertained by percent mammographic density (37,38) or MRI percent-water (16), including with our previous findings from the ALSPAC cohort showing strong associations between childhood growth and MRI percent-water (39).…”

Do Birth Weight and Weight Gain During Infancy and Early Childhood Explain Variation in Mammographic Density in Women in Midlife? Results From Cohort and Sibling Analyses

“…BMI and % body fat were also negatively associated with % fibroglandular volume as assessed by dual-energy x-ray absorptiometry in a study of 113 girls ages 10-16 years from Kaiser Permanente Hawaii (68). Even though other studies of MD have not looked at infant growth, a recent study examining growth trajectories from birth through adolescence and breast tissue composition as assessed by MRI in women at age 21 years observed a positive association between birth weight and MRI % water and inverse associations between pubertal weight growth and % body fat mass in adolescence and MRI % water (69). This analysis supported an association for later childhood and adolescent growth and MRI density measures but was consistent with our findings before adjusting for these later-life measures (70).…”

Constitutional BRCA1 Methylation and Risk of Incident Triple-Negative Breast Cancer and High-grade Serous Ovarian Cancer

“…Prenatal events have been assoc iated w ith risk of breast c ancer, as well as other cancers. [39][40][41] Thus, this study's findings should trigger further research assessing the potential association of constitutional methylation of other genes with the risk of other cancer types and research into the cause(s) of constitutional normal tissue methylation of tumor suppressor genes.…”