Abstract PR-4: Increased odds of family history for triple negative breast cancer in Mexican American but not African American women

Recently Hines et al. reported differences in the association between breast cancer tumor markers and family history according to ethnicity (CEBP 2008 Oct;17(10):2700–6). Family history was significantly associated with estrogen receptor (ER)-negative tumors among Hispanic women with no similar relationship for non-Hispanic whites. Hines et al. argue for ethnic-specific predisposing genetic risk factors that may influence the pattern of disease within a group. Using data on Mexican American (MA) women from the Ella Binational Breast Cancer Study (N=260) and equivalent data on African American (AA) women (N=206), we assessed the association between family history and tumor subtype within each ethnic group. Family history was defined as self-reported history of breast or ovarian cancer in a relative under age 50. Medical record abstraction yielded tumor marker data for ER, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). Cut points for ER and PR negativity were set at ≥5%, and tumors negative for all three markers were considered to be triple negative breast cancer (TNBC). Using a case-only analysis, we found a significantly increased odds of family history for those with TNBC compared to non-TNBC among MA women (OR, 2.2; 95% CI, 1.1–4.6), adjusting for age at diagnosis. In contrast, no significant relation between family history and TNBC was observed for AA women (OR, 0.9; 95% CI, 0.4–2.1). Furthermore, we observed a difference in the association between age at diagnosis and TNBC between these two ethnic groups. MA women with TNBC were diagnosed at a significantly younger age than non-TNBC cases (OR, 6.1; 95% CI, 1.8–24.1), while there was no such association among AA cases (OR, 1.5; 95% CI, 0.5–4.5). In light of these findings, we suspect that there is a strong inherited component of risk for TNBC among MA but not AA women. These results support the observation of Hines et al. that ethnicity may modify the relationship between family history and tumor subtype-specific risk. The strong association between family history and TNBCs, which are enriched for basal-like tumors, in MA cases is most consistent with a higher burden of BRCA1 mutation carriers in the MA case-series than the AA cases. This observation is supported by the findings of Weitzel et al. (CEBP 2007 Aug;16(8):1615–20) that suggest that the presence of BRCA mutations may account for a higher proportion of breast cancers in young MA women, similar to that of women of Ashkenazi ancestry, compared to non-Hispanic white and AA women. These data strengthen the arguments to investigate the relative contribution of BRCA-specific mutations in breast cancers arising among MA women and to improve their resources for testing, counseling, and risk prevention. Given the recognized differences in responsiveness to chemotherapy among germline BRCA1 carriers, which are important in treatment planning, future research efforts should include cost-effective mutation analyses and genetic test result delivery in this population, especially in women with TNBC diagnosed before age 50.