Molecular differences between the triple negative tumors of African-American women and white women.

Abstract

Abstract Abstract #2087 Purpose. We recently reported associations between triple negative tumors (TNTs) and several key cell-cycle proteins. TNTs have also been associated with: 1) younger age and African-American (AA) race, 2) a relative lack of therapeutic targets, and 3) higher recurrence and poorer survival relative to other tumor subtypes. Furthermore, AA women diagnosed with TNTs experience worse outcomes than white women. TNTs are a mixed group of tumors that includes both basal and non-basal types. Markers that could help differentiate tumors with the poorest outcome would be of great use in determing how to effectively treat women with TNT. This study examines whether there are racial differences in key cell-cycle and apoptotic proteins among women with TNTs and could help to identify potential molecular mechanisms underlying racial disparities in these aggressive tumors.
 Methods. Invasive TNTs from a population-based cohort of 136 Atlanta women (56 AA and 79 white) aged 20–54, diagnosed between 1990 and 1992, were centrally reviewed and immuno-histochemically analyzed for ER, PR, HER2, Bcl2, Cyclins D1 and E, pRb, p16, p21, p27, p53, p130, Ki67, and apoptotic index (AI). Weighted frequency distributions, Chi-square tests, and logistic regression were used to assess racial differences. Age and stage-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated.
 Results. Among the 136 women diagnosed with TNTs, AA women were significantly more likely than white women to present at a later stage, with larger tumors, and increased grade, mitotic activity, tumor necrosis, and apoptotic index. AA women were also significantly younger, poorer, and obese. Cell cycle protein differences between AA and white women diagnosed with TNTs included higher expression of Cyclin E [OR = 4.0 (95% CI=1.9, 8.5)], pRB [OR = 2.8 (95% CI=1.6, 4.9)], p16 [OR = 2.2 (95% CI=1.3,3.8)], p21 [OR = 2.0 (95% CI=1.1, 3.5)], AI [OR = 2.1 (95% CI=1.3, 3.9)], and lower expression of p130 [OR = 0.6 (95% CI=0.3, 1.0)].
 Conclusions. Exclusively among triple negative tumors, we identified racial differences in expression levels of several key cell-cycle and apoptotic related proteins. Combined with other poor prognostic factors, these differences may account for racial disparities in outcome. Future etiologic studies and clinical trials dedicated to TNTs should consider underlying molecular differences. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2087.