We previously reported a high population-based prevalence of triple negative (TN) breast tumors among younger black women (46.7%) compared to white women (21.7%) diagnosed with primary unilateral invasive breast cancer. TN tumors do not express estrogen receptor (ER), progesterone receptor (PR), or Human Epidermal Growth Factor Receptor 2 (HER2). This lack of viable therapeutic targets for TN tumors (ER-PR-HER2-) may contribute to poor outcome for all women and to the inferior survival rates observed for black women. This study extends our prior findings to assess the association of race and triple subtypes with breast cancer survival; adjusting for socio-demographic, prognostic, and treatment factors (surgery, chemotherapy, radiotherapy, hormonal therapy, and delay). >Methods >Breast tumors from a population-based cohort of 117 black and 362 white Atlanta women aged 20-54, diagnosed from 1990 to 1992 were centrally reviewed and immuno-histochemically analyzed for ER, PR, and HER2; then sub grouped (TN, ER-PR-HER2+, ER+/PR+HER2+, ER/PR+HER2-). Other prognostic and treatment factors and vital status through 1/1/03 were obtained from medical records, the Atlanta cancer registry, and interviews. Survival analyses, overall and within triple subgroups, were conducted using Weighted Cox regression. >Results >TN tumors remained more prevalent among black women than white women, after adjustment for age, stage, grade, and poverty index (Odds Ratio [OR] =1.9, 95%Confidence Interval [CI] 1.2-2.9). Mortality was higher for black women overall (Hazard Ratio [HR] =1.9, 95% CI, 1.5-2.5) and differed by triple sub-groups (p<0.001), with survival poorest for TN and ER-PR-HER2+ sub-groups. Adjustment for triple subgroup, as well as age, stage, grade, poverty index, and treatment factors attenuated the racial difference in mortality (HR=0.9, 95% CI 0.6-1.2). However, within the TN subgroup, racial differences in survival persisted, after adjustment (HR=2.1, 95% CI 1.1-3.9). Survival disparity was diminished and no longer statistically significant for the remaining subgroups. The TN subgroup was also uniquely associated with high tumor grade, mitotic index, p16, and p53; low expression of Bcl-2 and Cyclin D1, and was rare in tumors < 1.0 cm. >Conclusions >The high prevalence of triple negative tumors among younger women and particularly younger black women, along with the poorer survival noted with these breast cancers, suggests different gene-environment etiologies with an inextricable connection to prognosis. Poverty, tumor biology, and treatment impact overall survival, but do not explain the poorer survival experienced by black women with the TN subtype. The increased risk of death from TN breast cancers, and two-fold increased risk of death for black women with TN tumors, emphasizes the need for better characterization of TN signatures in order to inform etiology and prognosis and perhaps identify targeted therapies to improve outcome.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA