Influence of high-dose estrogen exposure during adolescence on mammographic density for age in adulthood

High-dose estrogen exposure during adolescence has been hypothesized to increase a woman's breast cancer risk, possibly mediated through an increase in mammographic density, a well-established breast cancer risk factor. In 2006 to 2007, we conducted a retrospective study of women assessed for tall stature as an adolescent between 1959 and 1993. Eligible participants were ages ¡Ý40 years and treated during adolescence with 3 mg diethylstilbestrol or 150 ¦Ìg ethinyl estradiol daily or untreated. Mammograms from 167 treated and 142 untreated women were digitized. Total breast area, dense area, nondense area, and percent density were measured using a computer thresholding technique. Data on potential determinants were collected from medical records and telephone interview. Treated women had, on average, 17% lower dense area (P = 0.032). Means (95% confidence intervals) adjusted for age and body mass index for treated and untreated women were 24.5 cm2 (21.8-27.2) and 29.1 cm2 (26.0-32.4), respectively. There was no difference in adjusted means (95% confidence intervals) between treated and untreated women for nondense area [71.7 cm2 (66.2-77.7) versus 70.5 cm2 (64.7-76.9); P = 0.78], percent dense area [24.8% (22.4-27.4) versus 27.7% (24.8-30.7); P = 0.16], or total area [105.6 cm2 (100.1-111.4) versus 109.3 cm2 (103.1-115.8); P = 0.41], respectively. High-dose estrogen exposure during adolescence appears to curtail growth of mammographically dense tissue and therefore is unlikely to increase breast cancer risk through mechanisms related to mammographic density.