Molecular breast cancer subtypes in premenopausal and postmenopausal African-American women: Age-specific prevalence and survival
Molecular breast cancer subtypes in premenopausal and postmenopausal African-American women: Age-specific prevalence and survival
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DOI：
10.1016/j.jss.2007.03.085
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发表时间：
2007-11-01
影响因子：
2.2
通讯作者：
Frederick, Wayne A.
中科院分区：
文献类型：
--
作者：
Ihemelandu, Chukwuemeka U.;Leffall, LaSalle D.;Frederick, Wayne A.
背景。乳腺癌目前被视为一种异质性疾病，通过基因表达分析可分为多种分子亚型。这些分子亚型包括：基底细胞样型、人表皮生长因子受体2（Her - 2/neu）型、腔面A型和腔面B型。
目的。分析绝经前和绝经后非洲裔美国女性乳腺癌分子亚型的患病率及其与临床病理的关联。
设计。对1998年至2005年期间所有被诊断患有乳腺癌且雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（Her - 2/neu）状态数据可评估的非洲裔美国女性进行回顾性分析。分子亚型分类是基于从霍华德大学肿瘤登记处获取的每位患者的雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（Her - 2/neu）状态的免疫组化替代指标进行的。分子亚型定义如下：腔面A型（ER + 和/或PR +，HER2 -），腔面B型（ER + 和/或PR +，HER2 +），基底细胞样型（ER -，PR -，HER2 -）以及人表皮生长因子受体2（Her - 2/neu）型（ER -，PR -，且HER2 +）。
结果测量。我们分析了非洲裔美国女性人群中乳腺癌分子亚型的患病率，并确定了它们与患者人口统计学特征以及临床病理变量（淋巴结状态、肿瘤大小、组织学分级、p53突变状态和乳腺癌特异性生存率）的关联。
结果。在我们的研究样本中，腔面A型是最常见的亚型（55.4%），相比之下，腔面B型为（11.8%），基底细胞样型为（21.2%），人表皮生长因子受体2（Her - 2/neu）型为（11.6%）。分子亚型在绝经状态方面没有差异。然而，当按年龄分组时，在＜35岁年龄组中，基底细胞样型（57.1%）是最常见的，而腔面A型、腔面B型和人表皮生长因子受体2（Her - 2/neu）型分别为25.0%、14.3%和3.6%。基底细胞样型还呈现出年龄特异性的双峰分布，在＜35岁和51 - 65岁年龄组出现峰值。与腔面A型相比，基底细胞样型和人表皮生长因子受体2（Her - 2/neu）型与临床病理变量的关联性增加，预示着更具侵袭性的临床病程。在分子亚型中注意到p53和Bcl - 2原癌蛋白的表达之间存在一种矛盾的反向关系。分子亚型之间的乳腺癌特异性生存率存在显著差异（P＜0.04），基底细胞样型和人表皮生长因子受体2（Her - 2/neu）型的预后最差。
结论。在＜35岁的年轻绝经前非洲裔美国女性中基底细胞样型的高患病率可能是该组患者乳腺癌预后较差的一个促成因素。（c）2007爱思唯尔公司。保留所有权利。
Background. Breast cancer is currently regarded as a heterogeneous disease classified into various molecular subtypes using gene expression analysis. These molecular subtypes include: basal cell-like, Her-2/neu, luminal A, and luminal B.Objectives. To analyze the prevalence and clinicopathologic associations for molecular breast cancer subtypes in premenopausal and postmenopausal African-American women.Design. A retrospective analysis of all African-American women diagnosed with breast cancer from 1998 to 2005, who had assessable data for ER, PR, and Her-2/neu status. Molecular subtype classification was done based on immunohistochemical surrogates for ER, PR, and Her-2/neu status obtained from Howard University tumor registry for each patient. The molecular subtypes were defined as: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-), and Her-2/neu (ER-, PR-, and HER2+).Outcome Measures. We analyzed the prevalence of molecular breast cancer subtypes in a population of African-American women and determined their associations with patient demographics and clinicopathologic variables: node status, tumor size, histological grade, p53 mutation status, and breast cancer-specific survival.Results. The luminal A subtype was the most prevalent in our study sample (55.4%) compared with (11.8%) luminal B, (21.2%) basal cell-like and (11.6%) Her-2/ neu subtypes. The molecular subtypes did not differ by menopausal status. However, when stratified into age-specific groups, the basal cell-like subtype (57.1%) was the most prevalent in the age group < 35 y compared with luminal A, luminal B, and Her-2/neu subtypes at 25.0%,14.3%, and 3.6%, respectively. The basal cell-like subtype also showed an age-specific bimodal distribution with a peak in the < 35 y and 51 to 65 y age groups. The basal cell-like and the Her-2/neu subtypes showed an increased association with clinicopathologic variables portending a more aggressive clinical course when compared with luminal A subtype. A paradoxical inverse relationship between the expression of p53 and Bcl-2 protooncoprotein was noted in the molecular subtypes. Breast cancer-specific survival differed significantly among the molecular subtypes (P < 0.04), with the basal cell-like and Her-2/neu subtypes having the poorest outcome.Conclusions. The high prevalence of the basal cell-like subtype in the young premenopausal African-American women aged < 35 y could be a contributory factor to the poorer prognosis of breast cancer observed in this cohort of patients. (c) 2007 Elsevier Inc. All rights reserved.