Steroid hormone receptors in breast cancer management
Steroid hormone receptors in breast cancer management
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DOI：
10.1023/a:1006132427948
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发表时间：
1998-01-01
影响因子：
3.8
通讯作者：
Osborne, CK
中科院分区：
文献类型：
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作者：
Osborne, CK
雌激素和孕激素受体（ER和PR）在乳腺癌临床研究已有20多年。阳性受体状态与良好的预后特征相关，包括较低的细胞增殖率和肿瘤分化的组织学证据。在诊断后的最初几年，er阳性肿瘤患者的复发率往往较低；然而，这与随后几年较高的复发率相平衡，因此受体状态的总体预后意义不大。ER和PR在预测对激素治疗的反应方面具有最大的效用，无论是在辅助治疗环境中还是在晚期疾病中。如果检测方法正确，并且通过对接受内分泌治疗的患者的临床研究确定了er阴性和阳性的临界值，受体状态对于确定不太可能从激素治疗中获益的患者群体非常有帮助。同时表达ER和PR的肿瘤从激素治疗中获益最大，但仅表达ER或PR的肿瘤仍有显著的应答。现在已经确定了两种雌激素受体，ER α和ER β。尽管这些受体形式之间存在相当大的同源性，但它们似乎具有重要的结构和功能差异，这可能对组织和启动子特异性基因表达的调节很重要。这些受体形式，以及内质网变异和突变，也可能有助于激素敏感性和抗性。PR也以PRA和PRE两种形式存在。PRA似乎对PRE和ER α都有抑制作用，临床乳腺肿瘤中PRA与PRE的比例是否与临床相关还有待研究。受体相互作用蛋白的表达也可以调节内质网的转录活性，这些也需要进一步的研究来确定它们是激素敏感性还是抗性的标志。总之，ER和PR状态是帮助医生个体化治疗的重要生物标志物。
Estrogen and progesterone receptors (ER and PR) have now been studied in clinical breast cancer for more than 20 years. Positive receptor status correlates with favorable prognostic features including a lower rate of cell proliferation and histologic evidence of tumor differentiation. During the first several years after diagnosis, patients with ER-positive tumors tend to have a lower recurrence rate; however, this is balanced by a higher recurrence rate in subsequent years so that the overall prognostic significance of receptor status is modest. ER and PR have their greatest utility in predicting response to hormonal therapy, both in the adjuvant setting and for advanced disease. When the assay is done properly and cut-offs for ER-negativity and positivity are defined by clinical studies of patients treated with endocrine therapy, receptor status is very helpful in identifying groups of patients who are very unlikely to benefit from hormonal therapy. Tumors that express both ER and PR have the greatest benefit from hormonal therapy, but those containing only ER or only PR still have significant responses.Two types of estrogen receptors, ER alpha and ER beta, have now been identified. Although there is considerable homology between these receptor forms, they appear to have important structural and functional differences that may be important for tissue and promoter-specific regulation of gene expression. These receptor forms, as well as ER variants and mutants, may also contribute to hormonal sensitivity and resistance. PR also exists in two forms, PRA and PRE. PRA appears to have repressor functions on both PRE and ER alpha, and the ratio of PRA to PRE in clinical breast tumors needs to be studied for its possible clinical relevance. Expression of receptor-interacting proteins can also modulate ER transcriptional activity, and these too need additional study to determine if they are markers of hormonal sensitivity or resistance. In summary, ER and PR status are important biomarkers that help physicians individualize therapy.