Race and the poor prognosis basal breast tumor (BBT) phenotype in the population-based Carolina Breast Cancer Study (CBCS)

Abstract

9510 Background: Gene expression arrays reveal several breast cancer (BrCa) subtypes, with the basal-like subtype (BBT) carrying a poor prognosis (Sorlie T, PNAS 2003). Multiple BrCa microarray datasets (Sorlie et al PNAS 2003; van't Veer et al, Nature 2002; Sotiriou et al, PNAS 2003) suggest that 90% of BBT are ER-negative, PR-negative, and HER-2 nonamplified (Perou C, unpublished). Thus, this “triple negative” phenotype may be used to identify and determine the frequency of BBT. Methods: Data were obtained from the CBCS, a population-based case-control study of BrCa causation among African-American (AA) and non-African American (nonAA) women. The CBCS oversampled AA and women under the age of 50. HER-2 was determined by UNC Lineberger Immunohistochemistry (IHC) Core. We determined the proportion of triple negative BrCa by race (AA vs. non-AA) and by stage, mitotic index (>10 vs. ≤10) nuclear grade and histologic grade (grade 3 vs. 1–2). Results: 657 incident BrCa were evaluated from Phase I of the CBCS, including 260 AA and 397 nonAA women. 26.2% of all BrCa were triple negative, however this phenotype was significantly more frequent in AA (33.9% vs. 21.2%, p=0.0003), premenopausal women (30.3% vs. 21.9%, p=0.02), mitotic index > 10 (45.8% vs. 11.3%, p<0.0001), and nuclear or histologic grade 3 tumors (p=0.0001). The highest prevalence of triple negative BrCa occurred among premenopausal AA women (44.3%) compared with postmenopausal AA women (24.6%) (p=0.0008). In multivariate models combining all factors, the significant predictors of the triple negative phenotype were high mitotic index (p<0.0001), high nuclear or histologic grade (p<0.0001 both), and race (p=0.03). Conclusions: The poor-prognosis BBT subtype is strongly associated with high proliferative capacity (mitotic index > 10) and nuclear pleomorphism. In a large population-based study, the triple negative phenotype characteristic of BBT is markedly more common in AA women, particularly premenopausal AA women. The high proportion of BBT likely plays a role in the poor prognosis experienced by AA women with BrCa. (supported by NCI (SPORE CA58223), NIH (GCRC MO1RR00046). No significant financial relationships to disclose.