[PIK3CA gene mutations in Chinese women with HR+/HER2- breast cancer].

Objective: To investigate the spectrum of PIK3CA gene mutations in Chinese women with hormone receptor positive and HER2 negative (HR+/HER2-) breast cancer, to provide the genetic evidence for identifying potential beneficiaries from specific PI3K isoform inhibitors in Chinese women with breast cancer and to develop detection strategies. Methods: A total of 365 breast cancer specimens archived at the Peking Union Medical College Hospital, Beijing, China from January 2017 to October 2017 were screened. Among these patients, 186 HR+/HER2- women with invasive breast cancer were collected. PIK3CA gene mutations were detected using next generation sequencing technology. The gene variant features were then analyzed and compared with reported data. Results: Among the 186 HR+/HER2- breast cancer cases, 40 (21.5%,40/186) cases harbored PIK3CA gene mutations. Exons 9 and 20 of PIK3CA mutations occurred in 92.5%(37/40)of the tumors, which included E545K, E545G, Q546K, E542K, Q546R, P539R, E547D, H1047R, H1047L, H1047Q and N1044Y. Only one case harbored the exon 7 C420R mutation. Additionally, exons 1 (F83C) and 5 (G364R) uncommon mutations were discovered respectively in 2 cases. Based on the finding, 85.0% (34/40) of cases with known mutations could be detected using companion diagnostic methods. Moreover, 25.0% (10/40) of patients had two or three variants, which were composed of E726K/N345K, H1047Q/N345K, H1047R/G364R, H1047R/E453K, E545G/E726K, E542K/E726K, E542K/H1047R, E545K/H1047R/H1047L and E545K/E547D. The lymph node positive rate in these patients with PIK3CA mutation was remarkably higher than those without (i.e., wild type, P<0.05). Conclusions: In this group of HR+/HER2- breast cancer patients, common PIK3CA gene mutations account for the vast majority of the mutations. New rare variants in PIK3CA are also identified while their clinical significance needs to be further studied in a large cohort and/or multi-center study.目的： 探讨激素受体阳性/HER2阴性浸润性乳腺癌PIK3CA基因突变谱，为筛选潜在获益于靶向PI3K亚基特异性抑制剂的中国目标人群和制定检测策略提供参考。 方法： 收集2017年1月至10月存档于北京协和医院的乳腺癌手术标本365例，从中选取186例激素受体阳性/HER2阴性浸润性乳腺癌，以二代测序技术检测其PIK3CA基因突变，对比分析与已有报道变异类型之间的差异。 结果： 从186例激素受体阳性/HER2阴性乳腺癌中检出PIK3CA基因突变40例（21.5%，40/186）。其中位于第9号外显子和第20号外显子的突变占92.5%（37/40），包括E545K、E545G、Q546K、E542K、Q546R、P539R、E547D、H1047R、H1047L、H1047Q和N1044Y，仅有1例标本含有第7号外显子的C420R突变。另外，还发现2例涉及第1号外显子和第5号外显子罕见位点突变的标本，突变分别是F83C和G364R。研究共发现18种变异，根据数据，以伴随诊断方法可检出含已知突变的标本占比为85.0%（34/40）。在队列中，25.0%（10/40）的患者同时具有2种或3种突变，涉及的位点包括E726K/N345K、H1047Q/N345K、H1047R/G364R、H1047R/E453K、E545G/E726K、E542K/E726K、E542K/H1047R、E545K/H1047R/H1047L和E545K/E547D。PIK3CA突变型患者的淋巴结转移发生率明显高于PIK3CA野生型患者（P<0.05）。 结论： 标本中除了常见位点占PIK3CA基因突变的绝大多数外，还有新的罕见位点突变，其临床意义尚待扩大样本量、开展多中心及临床疗效相关性等研究以进一步确认。.