ESTROGEN-RECEPTOR MUTATIONS IN BREAST-CANCER
ESTROGEN-RECEPTOR MUTATIONS IN BREAST-CANCER
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DOI：
10.1002/jcb.240510204
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发表时间：
1993-02-01
影响因子：
4
通讯作者：
MCGUIRE, WL
中科院分区：
文献类型：
--
作者：
FUQUA, SAW;CHAMNESS, GC;MCGUIRE, WL
人们普遍认为，雌激素受体（ER）的存在可识别具有较低复发风险和较好总生存期的乳腺癌患者[Clark和McGuire，1988]，ER的测量已成为乳腺癌临床管理中的标准测定。受体状态也为那些可能对激素干预有反应的肿瘤提供了指导[McGuire 1978; Osborne et al.，1980; Rose等人，1985年]。但是，只有大约一半的ER阳性患者会对各种激素治疗产生反应，而那些最初有反应的患者，即使ER通常仍然存在，但在治疗一段时间后，大多数患者最终会发展为无反应性疾病。据估计，在稍后的日期再次活检的最初ER阳性肿瘤的ER损失仅为19% [Gross等人，1984年]。显然，通过配体结合试验对ER存在的简单测量不能为我们提供受体功能状态的充分估计。1985年，Sluyser和Mester假设某些乳腺肿瘤激素依赖性的丧失可能是由于存在突变或截短的类固醇受体，即使在没有激素的情况下也能激活转录[Sluyser和Mester，1985]。基于最近在人乳腺癌细胞系和肿瘤标本中鉴定出的几种ER序列变异，我们现在想提出这些鉴定的突变中的一些在体内受体功能障碍中起作用，并将回顾那些可能被证明在乳腺癌进展中重要的ER突变。
It is fairly well accepted that the presence of estrogen receptor (ER) identifies those breast cancer patients with a lower risk of relapse and better overall survival [Clark and McGuire, 1988], and the measurement of ER has become a standard assay in the clinical management of breast cancer. Receptor status also provides a guideline for those tumors which may be responsive to hormonal intervention [McGuire 1978; Osborne et al., 1980; Rose et al., 1985]. But only about half of ER-positive patients will respond to the various hormonal therapies available, and of those who do initially respond, most will eventually develop hormonally unresponsive disease following a period of treatment even though ER is often still present. Loss of ER from initially ER-positive tumors biopsied again at a later date has been estimated at only 19% [Gross et al., 1984]. Obviously the simple measurement of ER presence by ligand-binding assays does not provide us with an adequate estimate of the functional state of the receptor. In 1985 Sluyser and Mester hypothesized that the loss of hormone dependence of certain breast tumors may be due to the presence of mutated or truncated steroid receptors that activate transcription even in the absence of hormone [Sluyser and Mester, 1985]. Based on the recent identification of several ER sequence variants in human breast cancer cell lines and tumor specimens, we would now like to propose that some of these identified mutations play a role in receptor dysfunction in vivo, and will review those ER mutations which may prove to be important in breast cancer progression.