Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA

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Abstract
Background Breast cancers with a triple negative tumor (TNT) subtype (as defined by lacking protein expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)) preclude the use of available targeted therapies and may contribute to poor outcome and to the historically poorest survival observed among African–American (AA) women. This study examines association of the ER/PR/HER2 subtypes with race and breast cancer survival. Methods Breast tumors from a population-based cohort of 116 AA and 360 white Atlanta women aged 20–54, diagnosed from 1990 to 1992 were centrally reviewed and tested by immunohistochemistry. Multivariate survival analyses within subtypes (TNT, ER−PR−HER2+, ER+/PR+HER2+, ER+/PR+HER2−) were conducted using weighted Cox regression and included socio-demographic, prognostic, and treatment factors. Results TNTs were more prevalent among young women and particularly among AA women (Odds Ratio [OR] = 1.9, 95% Confidence Interval [CI] 1.2–2.9), adjusting for age, stage, grade, and poverty index. Overall mortality was higher for AA women (Hazard Ratio [HR] = 1.9, 95% CI, 1.5–2.5) and differed by subtypes (P < 0.001). Within the TNT subtype, racial differences in survival persisted, after additional adjustment for treatment and comorbidities (HR = 2.0, 95% CI 1.0–3.7). TNTs were uniquely associated with high expression of p16, p53, and Cyclin E; and low Bcl-2 and Cyclin D1 expression. Conclusions The high prevalence of TNTs among younger women and particularly younger AA women, along with unique protein expression patterns and poorer survival, suggests varying gene–environment etiologies with respect to age and race/ethnicity and a need for effective therapies.