High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients
High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients
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DOI：
10.1158/1078-0432.ccr-06-0248
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发表时间：
2006-08-01
影响因子：
11.5
通讯作者：
Jirstrom, Karin
中科院分区：
文献类型：
--
作者：
Stendahl, Maria;Ryden, Lisa;Jirstrom, Karin
目的：他莫昔芬长期以来一直是类固醇激素受体阳性乳腺癌辅助内分泌治疗的首选药物，由于其良好的有益作用，它仍然很重要。激素受体状态通常报告为“阳性”或“阴性”，使用10%阳性细胞核作为截止值。在这项研究中，我们的目的是评估是否进一步的激素受体状态的亚分类可以提高治疗predictedvalues.Experimental设计：雌激素受体（ER）和孕激素受体（PR）的免疫组化表达进行了定量的组织微阵列与肿瘤从500绝经前乳腺癌患者先前纳入一项随机试验的辅助他莫昔芬与未经治疗的对照组相比。我们的研究结果表明，在ER阳性细胞核>10%的肿瘤中，他莫昔芬的作用逐渐增强。然而，当根据不同PR分数分析他莫昔芬反应时，我们发现主要是PR阳性细胞核>75%的肿瘤患者对他莫昔芬治疗有反应，无复发率提高[相对风险，0.42（0.25-0.70）; P = 0.001]以及总体生存率[相对危险度，0.49（0.28-0.84）; P = 0.010]。结论：对于肿瘤显示> 75%PR阳性核的绝经前患者，辅助性他莫昔芬可改善无复发和总体生存率。在PR阳性细胞核较少的肿瘤中没有效果。PR是比ER更强的治疗反应预测因子。基于这些发现，我们建议在临床实践中实施一个分数，而不是二分法的激素受体免疫组化评价，可能更强调PR比ER。
Purpose: Tamoxifen has long been the drug of choice in adjuvant endocrine therapy of steroid hormone receptor - positive breast cancer, and it still remains important due to its well-documented beneficial effect. Hormone receptor status is often reported as "positive" or "negative" using 10% positive nuclei as a cutoff. In this study, we aimed to assess whether a further subclassification of hormone receptor status could enhance the treatment predictive value.Experimental Design: The immunohistochemical expression of estrogen receptor (ER) and progesterone receptor (PR) was quantified in tissue microarrays with tumors from 500 premenopausal breast cancer patients previously included in a randomized trial of adjuvant tamoxifen compared with an untreated control group.Results: Our findings show a gradually increasing tamoxifen effect in tumors with >10% ER-positive nuclei. However, when analyzing tamoxifen response according to various PR fractions, we found that it was primarily patients with tumors showing >75% PR-positive nuclei that responded to tamoxifen treatment, with an improved recurrence-free [relative risk, 0.42 (0.25-0.70); P = 0.001] as well as overall [relative risk, 0.49 (0.28-0.84); P = 0.010] survival.Conclusions: Adjuvant tamoxifen improved recurrence-free and overall survival for premenopausal patients with tumors showing >75% PR-positive nuclei. No effect could be shown in tumors with fewer PR-positive nuclei. The PR was a stronger predictor of treatment response than the ER. Based on these findings, we suggest the implementation of a fractioned rather than dichotomized immunohistochemical evaluation of hormone receptors in clinical practice, possibly with greater emphasis on the PR than the ER.