Abstract

Abstract A86 Obesity and weight gain during adulthood are associated with breast cancer risk. Recent studies suggest that body fatness at younger ages may be related to risk of breast cancer independently of adult adiposity, but this needs to be examined in further detail. We conducted a prospective analysis of body fatness during childhood and adolescence and risk of breast cancer in two established cohort studies, the Nurses’ Health Study (NHS) and the Nurses’ Health Study II (NHS II). Participants were 188,860 women who recalled their body fatness at ages 5, 10, and 20 using a validated 9-level pictogram, where level 1 represents the most lean and level 9 represents the most overweight. A total of 7582 cases of breast cancer were documented among these women during the follow-up period (1988-2004 for the NHS and 1989-2005 for the NHS II). Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for body fatness at each age and for average body fatness during childhood (ages 5-10) and adolescence (ages 10-20), adjusting for breast cancer risk factors. Initial analyses were conducted separately in the NHS and the NHS II; however, because none of the associations for body fatness at young ages differed significantly by cohort (P > 0.10 for all tests of heterogeneity), the data were combined. Body fatness at each age was inversely associated with risk of both premenopausal and postmenopausal breast cancer, and there were no significant interactions with menopausal status (P > 0.10). The multivariate RR for average adolescent body fatness ≥ level 5.5 compared to level 1 was 0.54 (95% CI: 0.37-0.78, P trend < 0.0001) for premenopausal breast cancer, and the comparable RR for postmenopausal breast cancer was 0.66 (95% CI: 0.53-0.82, P trend < 0.0001). When current body mass index (BMI) was included in the multivariate models, the associations for premenopausal breast cancer were slightly attenuated (RR for average adolescent body fatness ≥ level 5.5 compared to level 1 = 0.59, 95% CI: 0.41-0.86), whereas the associations for postmenopausal breast cancer became stronger (comparable RR = 0.60, 95% CI: 0.48-0.74). Among all women, adjusting for menopausal status as well as other risk factors, the multivariate RR for adolescent body fatness ≥ level 6.5 compared to level 1 was 0.57 (95% CI: 0.37-0.87, P trend < 0.0001). The inverse association for average adolescent body fatness was stronger for women who weighed less than 8.5 pounds at birth (multivariate RR for ≥ level 4.5 compared to level 1 = 0.64, 95% CI: 0.56-0.73, P trend < 0.0001) than for those who weighed 8.5 pounds or more (comparable RR = 0.89, 95% CI: 0.63-1.26, P trend = 0.05), and this interaction was statistically significant (P = 0.04). In addition, the inverse association for average adolescent body fatness was somewhat stronger for estrogen receptor negative (ER-) than for ER positive (ER+) tumors; the multivariate RR for ≥ level 4.5 compared to level was 0.56 (95% CI: 0.42-0.76) for ER- and 0.72 (95% CI: 0.63-0.83) for ER+ tumors (P for heterogeneity = 0.03), although both trends were highly significant (P < 0.0001). These findings confirm previous studies indicating that body fatness at young ages has a strong inverse association with risk of breast cancer throughout life, and they suggest that body fatness at young ages acts through a different biologic pathway than adult BMI. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A86.

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