Lund Mary Jo, Trivers Katrina F, Porter Peggy L, Coates Ralph J, Leyland-Jones Brian, Brawley Otis W, Flagg Elaine W, O'Regan Ruth M, Gabram Sheryl G A, Eley J William
Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road, NE, Atlanta, GA 30322, USA.
Breast Cancer Res Treat. 2009 Jan;113(2):357-70. doi: 10.1007/s10549-008-9926-3. Epub 2008 Mar 7.
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.
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.
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.
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.
三阴性肿瘤（TNT）亚型的乳腺癌（定义为缺乏雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）的蛋白表达）无法使用现有的靶向治疗方法，这可能导致预后不良，也是非裔美国（AA）女性中观察到的历来最差生存率的原因之一。本研究探讨ER/PR/HER2亚型与种族及乳腺癌生存率之间的关联。
对1990年至1992年间诊断的、年龄在20至54岁之间的116名AA女性和360名白人亚特兰大女性的基于人群队列中的乳腺肿瘤进行集中回顾，并通过免疫组织化学进行检测。在各亚型（TNT、ER-PR-HER2+、ER+/PR+HER2+、ER+/PR+HER2-）内进行多变量生存分析，采用加权Cox回归，纳入社会人口统计学、预后和治疗因素。
在调整年龄、分期、分级和贫困指数后，TNT在年轻女性中更为普遍，尤其是在AA女性中（优势比[OR]=1.9，95%置信区间[CI]1.2-2.9）。AA女性的总体死亡率更高（风险比[HR]=1.9，95%CI，1.5-2.5），且各亚型有所不同（P<0.001）。在TNT亚型中，在进一步调整治疗和合并症后，生存的种族差异仍然存在（HR=2.0，95%CI 1.0-3.7）。TNT与p16、p53和细胞周期蛋白E的高表达以及Bcl-2和细胞周期蛋白D1的低表达独特相关。
TNT在年轻女性尤其是年轻AA女性中的高患病率，以及独特的蛋白表达模式和较差的生存率，提示在年龄和种族/民族方面存在不同的基因-环境病因，并且需要有效的治疗方法。
