[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.