Quantitative association between, HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer
Quantitative association between, HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer
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DOI：
10.1093/jnci/95.2.142
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发表时间：
2003-01-15
期刊：
影响因子：
--
通讯作者：
Slamon, DJ
中科院分区：
文献类型：
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作者：
Konecny, G;Pauletti, G;Slamon, DJ
背景：HER-2/neu编码一种受体酪氨酸激酶，在20%-25%的人乳腺癌中扩增并过表达。这种肿瘤通常对激素治疗有抵抗力。尽管HER-2/neu扩增/过表达与雌激素受体（ER）和/或孕激素受体（PR）表达之间存在一般的负相关性，但一部分患者同时为HER-2/neu和激素受体（HR）阳性。激素治疗在这一群体中的有效性目前是一个有争议的问题。为了更好地理解HER-2/neu阳性和HR表达之间的关系，我们分析了HER-2/neu、ER和PR作为乳腺癌细胞系和两组原发性乳腺癌患者的连续变量。研究方法：用酶联免疫吸附试验（ELISA）和酶免疫分析（EIA）分别检测了14株转染HER-2/neu基因的人乳腺癌细胞系HER-2/neu和ER/PR的表达。对于临床研究人群，通过ELISA评估HER-2/neu蛋白水平（队列A，n = 665），并使用荧光原位杂交测定HER-2/neu基因拷贝数（队列B，n = 894）。通过EIA（队列A）或放射性配体结合（队列B）分析ER/PR表达。使用斯皮尔曼rho相关和卡方检验分析HER-2/neu和ER/PR表达之间的关联，使用Mann-Whitney U检验比较绝对水平。所有统计学检验均为双侧检验。结果如下：HER-2/neu基因转染的HR阳性人乳腺癌细胞系表达的ER和PR水平在统计学上显著低于亲本细胞系。在临床队列中，HER-2/neu过表达和基因扩增水平与ER/PR水平呈负相关（队列A [n = 112]：ER，r =-0.34，P
Background: HER-2/neu, which encodes a receptor tyrosine kinase, is amplified and overexpressed in 20%-25% of human breast cancers. Such tumors are often resistant to hormone therapy. Despite a general inverse association between HER-2/neu amplification/overexpression and estrogen receptor (ER) and/or progesterone receptor (PR) expression, a fraction of patients are both HER-2/neu- and hormone receptor (HR)-positive. The efficacy of hormone therapy in this group is currently a matter of debate. To better understand the relationship between HER-2/neu positivity and HR expression, we analyzed HER-2/neu, ER, and PR as continuous variables in breast cancer cell lines and two cohorts of primary breast cancer patients. Methods: HER-2/neu and ER/PR expression was analyzed by enzyme-linked immunosorbent assay (ELISA) and enzyme immunoassay (EIA), respectively, in 14 human breast cancer cell lines, some of which had been transfected with the HER-2/neu gene. For the clinical study population, HER-2/neu protein levels were assessed by ELISA (cohort A, n = 665), and HER-2/neu gene copy number was determined using fluorescence in situ hybridization (cohort B, n = 894). ER/PR expression was analyzed by EIA (cohort A) or radioligand binding (cohort B). Associations between HER-2/neu and ER/PR expression were analyzed using Spearman's rho correlation and the chi-square test, and absolute levels were compared using the Mann-Whitney U test. All statistical tests were two-sided. Results: HR-positive human breast cancer cell lines transfected with the HER-2/neu gene expressed statistically significantly lower levels of ER and PR than parental lines. In the clinical cohorts, levels of HER-2/neu overexpression and gene amplification were inversely correlated with ER/PR levels (Cohort A [n = 112]: for ER, r = -0.34, P