Predictive markers for efficacy of everolimus plus exemestane in patients with luminal HER2-negative metastatic breast cancer
Predictive markers for efficacy of everolimus plus exemestane in patients with luminal HER2-negative metastatic breast cancer
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DOI：
10.1007/s12032-018-1112-9
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发表时间：
2018-04-01
期刊：
影响因子：
3.4
通讯作者：
Saito, Mitsue
中科院分区：
文献类型：
--
作者：
Okazaki, Misato;Horimoto, Yoshiya;Saito, Mitsue
转移性乳腺癌（MBC）基本上是不可治愈的，尽管最近在全身治疗的改善。我们经常遇到困难，在选择最合适的治疗，最佳时机，为个别病人。依维莫司是mTOR抑制剂之一，通常与MBC的内分泌治疗一起使用。基于依维莫司的治疗的预测标志物的鉴定仍然是一个主要问题，但迄今为止，尚未建立预测标志物。我们回顾性研究了ER阳性和HER 2阴性乳腺癌患者接受依维莫司联合阿司美坦治疗的预测标志物。18例局部晚期疾病或MBC患者接受依维莫司加阿司美坦治疗，其临床病理学特征与治疗效果相关。此外，对所有ER阳性和HER 2阴性的原发性乳腺癌标本进行磷酸-S6（pS 6）和PTEN的化学分析，以评估mTOR和PIK 3CA/Akt途径。那些表现出良好的临床反应有一个显着较低的Ki 67标记指数比反应差。在pS 6水平中观察到类似的趋势，但没有统计学意义。有趣的是，Ki 67标记指数和pS 6之间没有相关性，当两个指数都低时，良好的临床反应率高。Ki 67标记指数低的患者的中位无进展生存期（109周）长于Ki 67标记指数高的患者（19周）。PTEN表达与治疗效果之间没有趋势。我们的研究结果表明，原发性肿瘤的管腔HER 2阴性乳腺癌患者与低Ki 67标记指数和pS 6水平有可能对依维莫司加阿司美坦反应良好。
Metastatic breast cancer (MBC) is essentially incurable despite recent improvements in systemic therapies. We often encounter difficulties in choosing the most appropriate treatments, with optimal timing, for individual patients. Everolimus, one of the mTOR inhibitors, is usually used with endocrine therapy for MBC. Identification of predictive markers for everolimus-based treatment remains a major issue, but to date, no predictive markers have been established. We retrospectively investigated predictive markers for treatments with everolimus plus exemestane in patients with ER-positive and HER2-negative breast cancer. Clinicopathological features of 18 patients, with locally advanced disease or MBC given everolimus plus exemestane treatments, were examined in relation to treatment effects. Also, primary breast cancer specimens, all ER positive and HER2 negative, were immunohistochemically investigated for phospho-S6 (pS6) and PTEN, to evaluate the mTOR and PIK3CA/Akt pathways. Those showing a good clinical response had a significantly lower Ki67 labeling index than the poor responders. A similar trend was observed in pS6 level but without statistical significance. Interestingly, there was no correlation between the Ki67 labeling index and pS6, and when both indexes were low, the good clinical response rate was high. The median progression-free survival was longer in the group showing a low Ki67 labeling index (109 weeks) than in that with high Ki67 (19 weeks). There was no trend between PTEN expression and treatment effects. Our results suggest that the primary tumor in luminal HER2-negative breast cancer patients with a low Ki67 labeling index and pS6 level has the potential to respond well to everolimus plus exemestane.