Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA
Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA
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DOI：
10.1007/s10549-008-9926-3
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发表时间：
2009-01-01
影响因子：
3.8
通讯作者：
Eley, J. William
中科院分区：
文献类型：
--
作者：
Lund, Mary Jo;Trivers, Katrina F.;Eley, J. William
背景：三阴性肿瘤（TNT）亚型乳腺癌（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）排除了现有靶向治疗的使用，可能导致预后不佳，并导致非裔美国人（AA）女性中历史上最低的生存率。本研究探讨了ER/PR/HER2亚型与种族和乳腺癌生存的关系。方法对1990 ~ 1992年诊断的116例AA和360例20 ~ 54岁亚特兰大白人女性的乳腺肿瘤进行集中分析和免疫组化检测。采用加权Cox回归对不同亚型（TNT、ER-PR-HER2+、ER+/PR+HER2+、ER+/PR+HER2-）进行多因素生存分析，包括社会人口学、预后和治疗因素。结果经年龄、分期、年级和贫困指数调整后，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%可信区间[CI] 1.2-2.9）。AA女性的总死亡率更高（危险比[HR] = 1.9, 95% CI, 1.5-2.5），且因亚型而异（P < 0.001）。在TNT亚型中，在对治疗和合并症进行额外调整后，生存率的种族差异仍然存在（HR = 2.0, 95% CI 1.0-3.7）。tnt与p16、p53和Cyclin E的高表达相关；低Bcl-2和Cyclin D1表达。结论：年轻女性，尤其是年轻AA女性中TNTs的高患病率，以及独特的蛋白表达模式和较差的生存率，表明不同年龄和种族/民族的基因环境病因不同，需要有效的治疗。
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.