A collaborative study of the etiology of breast cancer subtypes in African American women: the AMBER consortium

Cancer Causes and Control (Impact Factor: 2.96). 12/2013; 25(3). DOI: 10.1007/s10552-013-0332-8
Source: PubMed

ABSTRACT Breast cancer is a heterogeneous disease, with at least five intrinsic subtypes defined by molecular characteristics. Tumors that express the estrogen receptor (ER+) have better outcomes than ER- tumors, due in part to the success of hormonal therapies that target ER+ tumors. The incidence of ER- breast cancer, and the subset of ER- cancers that are basal-like, is about twice as high among African American (AA) women as among US women of European descent (EA). This disparity appears to explain, in part, the disproportionately high mortality from breast cancer that occurs in AA women. Epidemiologic research on breast cancer in AA women lags behind research in EA women. Here, we review differences in the etiology of breast cancer subtypes among AA women and describe a new consortium of ongoing studies of breast cancer in AA women.
We combined samples and data from four large epidemiologic studies of breast cancer in AA women, two cohort and two case-control, creating the African American Breast Cancer Epidemiology and Risk consortium. Tumor tissue is obtained and stored in tissue microarrays, with assays of molecular markers carried out at a pathology core. Genotyping, carried out centrally, includes a whole exome SNP array and over 180,000 custom SNPs for fine-mapping of genome-wide association studies loci and candidate pathways.
To date, questionnaire data from 5,739 breast cancer cases and 14,273 controls have been harmonized. Genotyping of the first 3,200 cases and 3,700 controls is underway, with a total of 6,000 each expected by the end of the study period.
The new consortium will likely have sufficient statistical power to assess potential risk factors, both genetic and non-genetic, in relation to specific subtypes of breast cancer in AA women.

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    ABSTRACT: African American (AA) women are more likely than white women to be obese and to be diagnosed with ER- and triple-negative (TN) breast cancer, but few studies have evaluated the impact of obesity and body fat distribution on breast cancer subtypes in AA women. We evaluated these associations in the AMBER Consortium by pooling data from four large studies. Cases were categorized according to hormone receptor status as ER+, ER-, and TN (ER-, PR-, and HER2-) based on pathology data. A total of 2104 ER+ cases, 1070 ER- cases (including 491 TN cases), and 12,060 controls were included. Odds ratios (OR) and 95 % confidence intervals (CI) were computed using logistic regression, taking into account breast cancer risk factors. In postmenopausal women, higher recent (most proximal value to diagnosis/index date) BMI was associated with increased risk of ER+ cancer (OR 1.31; 95 % CI 1.02-1.67 for BMI ≥35 vs. <25 kg/m(2)) and with decreased risk of TN tumors (OR 0.60; 95 % CI 0.39-0.93 for BMI ≥35 vs. <25). High young adult BMI was associated with decreased premenopausal ER+ cancer and all subtypes of postmenopausal cancer, and high recent waist-to-hip ratio with increased risk of premenopausal ER+ tumors (OR 1.35; 95 % CI 1.01-1.80) and all tumor subtypes combined in postmenopausal women (OR 1.26; 95 % CI 1.02-1.56). The impact of general and central obesity varies by menopausal status and hormone receptor subtype in AA women. Our findings imply different mechanisms for associations of adiposity with TN and ER+ breast cancers.
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