Estrogen receptor-positive, progesterone receptor-negative breast cancer: Association with growth factor receptor expression and tamoxifen resistance
Estrogen receptor-positive, progesterone receptor-negative breast cancer: Association with growth factor receptor expression and tamoxifen resistance
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DOI：
10.1093/jnci/dji249
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发表时间：
2005-09-07
影响因子：
10.3
通讯作者：
Elledge, RM
中科院分区：
文献类型：
--
作者：
Arpino, G;Weiss, H;Elledge, RM
背景资料：临床数据表明，雌激素受体阳性/孕激素受体阴性（ER+/PR-）乳腺癌对他莫昔芬的敏感性低于ER+/PR+肿瘤。也有报道称，他莫昔芬在过度表达HER-2或HER-1（表皮生长因子受体）的肿瘤中可能不太有效，并且通过这些受体的信号传导降低了实验模型中的PR表达。我们假设ER+/PR-乳腺肿瘤比ER+/PR+乳腺肿瘤更可能具有侵袭性表型，表达HER-1和过表达HER-2，并且不太可能从他莫昔芬辅助治疗中获益。方法：对31415例ER+/PR+肿瘤患者和13404例ER +/PR-肿瘤患者的临床和生物学特征进行比较。在11399例接受他莫昔芬辅助治疗的患者中分析了无病生存期（DFS）与HER-1和HER-2状态之间的关系。使用考克斯回归或Kaplan-Meier分析计算风险比（HR）和95%置信区间（CI），所有统计检验均为双侧检验。结果如下：ER+/PR-肿瘤在老年患者中更常见，体积更大，具有更高的S期分数，并且比ER+/PR+肿瘤更可能是非整倍体。此外，表达HER-1的ER+/PR-肿瘤是ER+/PR+肿瘤的三倍（25%对8%; P
Background: Clinical data indicate that estrogen receptor-positive/progesterone receptor-negative (ER+/PR-) breast cancers are less sensitive to tamoxifen than are ER+/PR+ tumors. It has also been reported that tamoxifen may be less effective in tumors that overexpress either HER-2 or HER-1 (epidermal growth factor receptor) and that signaling through these receptors reduces PR expression in experimental models. We hypothesized that ER+/PR- breast tumors are more likely than ER+/PR+ breast tumors to have an aggressive phenotype, to express HER-1 and overexpress HER-2, and are less likely to benefit from tamoxifen adjuvant therapy. Methods: Clinical and biological features of 31415 patients with ER+/PR+ tumors were compared with those of 13404 patients with ER+/PR- tumors. Association between disease-free survival (DFS) and HER-1 and HER-2 status was analyzed in a subset of 11399 patients receiving adjuvant tamoxifen therapy. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression or Kaplan-Meier analyses, and all statistical tests were two-sided. Results: ER+/PR- tumors were more frequent in older patients, were larger in size, had a higher S-phase fraction, and were more likely to be aneuploid than ER+/PR+ tumors. Furthermore, three times as many ER+/PR- tumors as ER+/PR+ tumors expressed HER-1 (25% versus 8%; P