Background: The V measure captures grayscale intensity variation on a mammogram and is positively associated with breast cancer risk, independent of percent mammographic density (PMD), an established marker of breast cancer risk. We examined whether anthropometrics are associated with V, independent of PMD. Methods: The analysis included 1,700 premenopausal and 1,947 postmenopausal women without breast cancer within the Nurses Health Study (NHS) and NHSII. Participants recalled their body fatness at ages 5, 10, and 20 years using a 9-level pictogram (level 1: most lean) and reported weight at age 18 years, current adult weight, and adult height. V was estimated by calculating standard deviation of pixels on screening mammograms. Linear mixed models were used to estimate beta coefficients ( ) and 95% confidence intervals (CI) for the relationships between anthropometric measures and V, adjusting for confounders and PMD. Results: V and PMD were positively correlated (Spearman r 1/4 0.60). Higher average body fatness at ages 5 to 10 years (level 4.5 vs. 1) was significantly associated with lower V in premenopausal (-0.32; 95% CI, -0.48 to -0.16) and postmenopausal (-0.24; 95% CI, -0.37 to -0.10) women, independent of current body mass index (BMI) and PMD. Similar inverse associations were observed with average body fatness at ages 10 to 20 years and BMI at age 18 years. Current BMI was inversely associated with V, but the associations were largely attenuated after adjustment for PMD. Height was not associated with V. Conclusions: Our data suggest that early-life body fatness may reflect lifelong impact on breast tissue architecture beyond breast density. However, further studies are needed to confirm the results. Impact: This study highlights strong inverse associations of early-life adiposity with mammographic image intensity variation.
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