Breast Cancer Population Attributable Risk Proportions Associated with Body Mass Index and Breast Density by Race/Ethnicity and Menopausal Status.

BACKGROUND: Overweight/obesity and dense breasts are strong breast cancer risk factors whose prevalences vary by race/ethnicity. The breast cancer population attributable risk proportions (PARP) explained by these factors across racial/ethnic groups are unknown. METHODS: We analyzed data collected from 3,786,802 mammography examinations (1,071,653 women) in the Breast Cancer Surveillance Consortium, associated with 21,253 invasive breast cancers during a median of 5.2 years follow-up. HRs for body mass index (BMI) and breast density, adjusted for age and registry were estimated using separate Cox regression models by race/ethnicity (White, Black, Hispanic, Asian) and menopausal status. HRs were combined with observed risk-factor proportions to calculate PARPs for shifting overweight/obese to normal BMI and shifting heterogeneously/extremely dense to scattered fibroglandular densities. RESULTS: The prevalences and HRs for overweight/obesity and heterogeneously/extremely dense breasts varied across races/ethnicities and menopausal status. BMI PARPs were larger for postmenopausal versus premenopausal women (12.0%-28.3% vs. 1.0%-9.9%) and nearly double among postmenopausal Black women (28.3%) than other races/ethnicities (12.0%-15.4%). Breast density PARPs were larger for premenopausal versus postmenopausal women (23.9%-35.0% vs. 13.0%-16.7%) and lower among premenopausal Black women (23.9%) than other races/ethnicities (30.4%-35.0%). Postmenopausal density PARPs were similar across races/ethnicities (13.0%-16.7%). CONCLUSIONS: Overweight/obesity and dense breasts account for large proportions of breast cancers in White, Black, Hispanic, and Asian women despite large differences in risk-factor distributions. IMPACT: Risk prediction models should consider how race/ethnicity interacts with BMI and breast density. Efforts to reduce BMI could have a large impact on breast cancer risk reduction, particularly among postmenopausal Black women.

Estrogen receptor alpha haplotypes and breast cancer risk in older Caucasian women.

Life-long exposure to estrogen is an established risk factor for breast cancer development. The underlying mechanism has been suggested to be the binding of estrogen-to-estrogen receptors in mammary tissue, which in turn promotes the proliferation and differentiation of breast tissue. Polymorphisms and haplotypes in estrogen receptor alpha (ESR1) have been reportedly associated with breast cancer risk; however, the results are not fully consistent. In this study, we investigated breast cancer risk associated with genotypes and haplotypes resulting from four ESR1 single nucleotide polymorphisms (SNPs), rs746432, rs2234693, rs9340799, and rs1801132. Genotyping has been performed on 393 breast cancer cases and 790 randomly selected controls in 1,183 Caucasian women over age 65 from the Study of Osteoporotic Fractures (SOF). We observed an allelic protective effect for SNP rs9340799 with an estimated odds ratio (OR) of 0.82 (95% CI = 0.68-1.00; P = 0.04) after adjustment for age, BMI and hip BMD. A protective effect of this SNP has been reported before in several different studies. We did not replicate the previously reported C-C-A-G haplotype association to breast cancer-the C-C-A-G haplotype from these SNPs was rare in this study (estimated frequency below 0.001% in cases and controls). No other statistically significant associations were observed between ESR1 haplotypes from the same four SNPs and the risk of breast cancer in older Caucasian women.