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    Research Grants Awarded

    Comparison of the IGF and Breast Density Association by Race

    Study Section:
    RISK and Prevention, Epidemiology

    Scientific Abstract:
    Background: Insulin-like growth factor (IGF)-I is a recognized mitogen for breast tissue. IGF binding protein-3 (IGFBP-3) binds IGF-I and regulates its biological activity. Among premenopausal Caucasian women, high levels of IGF-I are associated with higher breast density and breast cancer risk. One small study showed IGF-I to be related to breast cancer risk in postmenopausal African-American women. Having high breast density is associated increases breast cancer risk four to six-fold and is one of the strongest predictors of premenopausal and postmenopausal breast cancer. Even though premenopausal breast cancer rates are higher in African-American than Caucasian women the association between IGF-I, IGFBP-3 and breast density has not been studied in African-Americans. Since circulating IGF-I influences body fat distribution, and body mass index (BMI) is strongly associated with breast density, studies of breast density must take BMI into consideration. Including BMI is most important in a comparison of associations by race because the prevalence of being overweight and obese is higher among African-Americans than other ethnic groups in the US . Hypotheses: We hypothesize that increased breast density will be positively associated with IGF-1, and inversely associated with obesity and IGFBP-3 among all African-American but only premenopausal Caucasian women. Specific Aims: We will measure plasma IGF-I and IGFBP-3 in all study participants and compare this with measured breast density to determine the proportion of the variance in breast density among African-Americans and Caucasians women explained by body mass index, IGF-1 and IGFBP-3 by menopause status. Through statistical modeling we will also determine how variation in prevalence of these factors by race and menopause status could explain the differences in incident rates of breast cancer. Design: We will analyze blood samples that have already been collected from a cross-sectional study of 1152 women having mammograms in a large urban breast health center. Statistical analyses by race and menopausal status that control for important covariates will allow us to address these issues. Outcome: Our comparison of the associations between IGF-I, IGFBP-3, obesity and breast density among premenopausal and postmenopausal African-American and Caucasian women will help elucidate why the incident rates of breast cancer differ by race in the United States , and suggest pathways for prevention efforts.

    Lay Abstract:
    Background: Insulin-like growth factor (IGF)-I is involved in normal cellular replication processes and its biological activity is regulated in large part by IGF binding protein-3 (IGFBP-3). Previous studies have linked high levels of circulating IGF-I with high mammographic breast density and increased risk of breast cancer in premenopausal Caucasian women. IGF-I also influences weight gain, a factor known to be associated with breast cancer risk. Breast density is one of the strongest predictors of both premenopausal and postmenopausal breast cancer risk. Although African-American women are known to have higher rates of premenopausal breast cancer, higher rates of obesity, and higher levels of IGF-I, none of the studies linking all of these factors with breast density have been conducted among African-Americans. Hypotheses: We hypothesize that increased breast density will be associated with high levels of circulating IGF-1, and low levels of IGFBP-3 among all African-American but only premenopausal Caucasian women. Specific Aims: We will measure plasma IGF-I and IGFBP-3 levels in all study participants and compare these levels with measured breast density. Our analyses will determine how much of the differences in levels of breast density among African-Americans and Caucasians women can be explained by different distributions of body size, IGF-1 and IGFBP-3 by menopause status. We will develop statistical estimates to predict how variation in how common these factors are by race and menopause status could explain the known differences in breast cancer rates. Design: We will analyze blood samples that have already been collected, stored and frozen from a study of 1152 women having mammograms in a large urban breast health center. Statistical analyses by race and menopausal status that control for other important factors will allow us to address these issues. Outcome: Our comparison of the associations between IGF-I, IGFBP-3, obesity and breast density among premenopausal and postmenopausal African-American and Caucasian women will help explain why the rates of breast cancer differ by race in the United States , and suggest pathways for prevention efforts.