It has become increasingly clear that breast cancer is not a single disease entity, but a combination of distinct disease subtypes, with separate clinical outcomes and etiologic risk factors. American women of African ancestry (AA) have a higher mortality from breast cancer at all ages, are diagnosed more frequently at young ages, and have more aggressive tumors than women of European ancestry (EA). The reasons for these racial disparities are unclear, and existing studies of AA women lack the statistical power to investigate risk factors for breast cancer defined by early age at onset and tumor biology. Our ongoing studies have provided intriguing data regarding the relation of parity and lactation to risk of ER-/PR- breast cancer and to basal-like breast cancer. High parity appears to be associated with a strong increased risk of ER- and basal-like breast cancer in young women, with lactation removing most of the excess risk. There is also evidence that oral contraceptive use may be a stronger risk factor for ER- breast cancer than for ER+ cancer. AA women have an earlier age at menarche, are less likely to breastfeed their babies, and more likely to have their babies at a young age than are EA women. We propose to combine data, biospecimens, and expertise from four of the largest studies of breast cancer in AA women: the Black Women's Health Study, the Carolina Breast Cancer Study, the Women's Circle of Health Study, and the Multi-Ethnic Cohort. We will have over 6,671 AA breast cancer cases, with DNA available on 5,534 and tumor blocks on 4475. We will characterize breast tumors by intrinsic subtypes and then assess reproductive and hormonal factors in relation to risk of each subtype, including ER-/PR-, five intrinsic subtypes, and early onset breast cancer (before age 45). Using DNA samples from the four studies, we will genotype tagSNPs in genes in the steroid hormone pathway and assess their association with breast cancer subtypes. We will then assess how these genetic and reproductive factors interact to increase risk of early-onset, ER-, and basal-like breast cancer in AA women. We will also assess interactions with genetic markers found in Projects 1, 3, and 4 and explore the role of immune/inflammatory pathways in early aggressive breast cancer. If we confirm preliminary results that breastfeeding prevents the two-fold increase in risk of basal-like breast cancer in AA women, our results will have immediate public health impact for promotion of breastfeeding among AA women.
This project will assess the relation of reproductive factors such as age at menarche, number of births, and breastfeeding to risk of specific subtypes of breast cancer in women of African ancestry (AA). Genetic factors will also be assessed to explore how genetic susceptibility and reproductive history interact to influence risk of breast cancer subtypes. With our large sample size and ability to determine risk factors for early, aggressive breast cancer, our results may have immediate public health impact, particularly for prevention of basal-like breast cancer by breastfeeding.
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