Adult weight gain, fat distribution and mammographic density in Spanish pre- and post-menopausal women (DDM-Spain)

Abstract

High mammographic density (MD) is a phenotype risk marker for breast cancer. Body mass index (BMI) is inversely associated with MD, with the breast being a fat storage site. We investigated the influence of abdominal fat distribution and adult weight gain on MD, taking age, BMI and other confounders into account. Because visceral adiposity and BMI are associated with breast cancer only after menopause, differences in pre- and post-menopausal women were also explored. We recruited 3,584 women aged 45–68 years within the Spanish breast cancer screening network. Demographic, reproductive, family and personal history data were collected by purpose-trained staff, who measured current weight, height, waist and hip circumferences under the same protocol and with the same tools. MD was assessed in the left craniocaudal view using Boyd’s Semiquantitative Scale. Association between waist-to-hip ratio, adult weight gain (difference between current weight and self-reported weight at 18 years) and MD was quantified by ordinal logistic regression, with random center-specific intercepts. Models were adjusted for age, BMI, breast size, time since menopause, parity, family history of breast cancer and hormonal replacement therapy use. Natural splines were used to describe the shape of the relationship between these two variables and MD. Waist-to-hip ratio was inversely associated with MD, and the effect was more pronounced in pre-menopausal (OR = 0.53 per 0.1 units; 95 % CI = 0.42–0.66) than in post-menopausal women (OR = 0.73; 95 % CI = 0.65–0.82) (P of heterogeneity = 0.010). In contrast, adult weight gain displayed a positive association with MD, which was similar in both groups (OR = 1.17 per 6 kg; 95 % CI = 1.11–1.23). Women who had gained more than 24 kg displayed higher MD (OR = 2.05; 95 % CI = 1.53–2.73). MD was also evaluated using Wolfe’s and Tabár’s classifications, with similar results being obtained. Once BMI, fat distribution and other confounders were considered, our results showed a clear dose–response gradient between the number of kg gained during adulthood and the proportion of dense tissue in the breast.

Anthropometric factors, adult weight gain, and mammographic features

“…The negative association we observed between anthropometric factors and percent density or dense area is consistent with the literature [21][22][23][24][25][26][27][28][29][30], although more conflicting results are reported for dense area [21,[24][25][26][27][28][29][30], possibly due to important variation in the adjustments performed in the analyses. Interestingly, this inconsistency is also illustrated in our results by the inversion of the correlations between adiposity and dense area after adjustment for non-dense area.…”

“…BMI, waist circumference, or WHR has been shown to be negatively associated with percent density [21][22][23][24][25][26][27][28][29][30] or absolute dense area [24-26, 29, 30], although not consistently for the latter [21,27,28], while positively associated with absolute non-dense area [21,[24][25][26][27][28][29][30]. Meanwhile, the association between weight gain during adulthood and breast density was seldom studied and led to inconsistent results [21][22][23].…”

“…Meanwhile, the association between weight gain during adulthood and breast density was seldom studied and led to inconsistent results [21][22][23]. The apparent paradox is that absolute nondense area seems negatively associated with breast cancer risk but is positively associated with factors reflecting total or abdominal body fatness that are risk factors for breast cancer.…”

Genome wide association study identifies a novel putative mammographic density locus at 1q12‐q21

“…In fact, BMI, a measurement closely related with height, is also associated with MD. 26,27 Another study 28 found that rs11205277 was associated with two stages of height growth, the peak height velocities in infancy (PHV1) and the puberty (PHV2). Moreover Lei et al 29 confirmed the association of this SNP with stature.…”

“…While visual reading evaluates the image as a whole and may overestimate MD, semi-automatic methods compute the percentage of dense tissue taking the whole area limited by the skin into account, including the subcutaneous fat tissue that is not part of the mammary gland. 26,27 This, in turn, may imply a greater agreement between visual assessment and the absolute dense area that is not influenced by the amount of subcutaneous fat.…”