Adiposity Change Over the Life Course and Mammographic Breast Density in Postmenopausal Women

Abstract

◥Mammographic breast density is a strong risk factor for breast cancer. We comprehensively investigated the associations of body mass index (BMI) change from ages 10, 18, and 30 to age at mammogram with mammographic breast density in postmenopausal women. We used multivariable linear regression models, adjusted for confounders, to investigate the associations of BMI change with volumetric percent density, dense volume, and nondense volume, assessed using Volpara in 367 women. At the time of mammogram, the mean age was 57.9 years. Compared with women who had a BMI gain of 0.1-5 kg/m 2 from age 10, women who had a BMI gain of 5.1-10 kg/m 2 had a 24.4% decrease [95% confidence interval (CI), 6.0%-39.2%] in volumetric percent density; women who had a BMI gain of 10.1-15 kg/m 2 had a 46.1% decrease (95% CI, 33.0%-56.7%) in volumetric percent density; and women who had a BMI gain of >15 kg/m 2 had a 56.5% decrease (95% CI, 46.0%-65.0%) in volumetric percent density. Similar, but slightly attenuated associations were observed for BMI gain from ages 18 and 30 to age at mammogram and volumetric percent density. BMI gain over the life course was positively associated with nondense volume, but not dense volume. We observed strong associations between BMI change over the life course and mammographic breast density. The inverse associations between early-life adiposity change and volumetric percent density suggest that childhood adiposity may confer long-term protection against postmenopausal breast cancer via its effect of mammographic breast density.

Deciphering how early life adiposity influences breast cancer risk using Mendelian randomization

“…Moreover, higher adiposity in childhood and adolescence has been associated with lower MD throughout adulthood [24]. In light of several recent studies [64], [65] suggesting a plausible role of MD in the mediation of the protective effect of childhood body size on breast cancer risk, applying our MR framework to these datasets is an important aim for the future. We were also unable to perform the full analysis on breast size data.…”

Changes in adiposity over the life course and gene expression in postmenopausal women

“… 7 The exclusion criteria were (a) any cancer history, including breast cancer; (b) history of breast implants, augmentation, or reduction; and (c) use of selective estrogen receptor modulators (SERM) or denosumab in the previous 6 months. 7 …”

“…On the day of the appointment, each study participant completed a blood draw by trained phlebotomists and filled in breast cancer risk factor questionnaires. 7 We excluded 16 women with missing gene expression data and 12 women with missing BMI or body shape at age 10; thus, we had 372 postmenopausal women in our final analysis. This study obtained institutional review board (IRB) approval from Washington University School of Medicine, and documented consent was obtained from all participants.…”

“…28 Then, we estimated BMI at age 10 using the Growing Up Today Study. 7 , 29 Since the 9‐level figure somatotype pictogram for girls in the Growing Up Today Study ranged from 1 to 7, we did not compute BMI at age 10 for women whose body shape at age 10 was larger than 7. We calculated BMI at ages 18, 30, and at the time of mammogram by dividing weight in kilograms at each age with height in meters squared.…”

“… 6 Furthermore, we and others have demonstrated that early life adiposity and long‐term adiposity gains from ages 10 and 18 are associated with breast cancer and mammographic breast density among postmenopausal women. 7 , 8 , 9 , 10 , 11 However, the underlying biological mechanisms driving the associations of early life adiposity with mammographic breast density and breast cancer are largely unknown.…”