Abstract
PURPOSE: PIK3CA gene mutations have been identified in various malignancies, but the prevalence of specific mutations and their role in breast cancer development remain uncertain. This study aimed to investigate the clinicopathological significance and prognostic impact of PIK3CA mutations in breast cancer. METHODS: Five common PIK3CA mutations (H1047R and H1047L in exon 20, and E542K, E545K, and E545D in exon 9) were identified in breast cancer patients using amplification refractory mutation system (ARMS) allele-specific PCR. The study examined the relationships between these mutations and clinicopathologic factors, such as age, HR status, Her2 status, lymph node involvement, distant metastasis, clinicopathologic stage, and progression-free survival (PFS). RESULTS: A total of 40 female breast cancer patients were included in this study. Twenty mutations were detected, with 12 located in exon 20 and 8 in exon 9. The most frequent mutation was H1047R in exon 20, present in 11 patients (14.8%). PIK3CA mutations were more commonly observed in patients with HR + breast cancer (P < 0.05). No significant correlation was found between PIK3CA mutations and age, Her2 status, lymph node involvement, distant metastasis, clinicopathologic stage, or Ki-67 expression. Database analysis from the cBioPortal online database showed that the median PFS (95%CI) of the PIK3CA unaltered group [22.93 (17.25-48.30) months] was higher than that of the altered group [12.98 (8.18-18.14) months]. In this study, PIK3CA mutant-type group [13.00 (10.56-15.45) months] had lower median PFS than that of the wild-type group [25.00 (13.46-36.55) months] in all breast cancer patients, the difference was significant (P = 0.004). Further, compared with PIK3CA wild-type, mutant-type was associated with poor PFS in HR + and Her2 + breast cancer patients (P < 0.05). In addition, positive H1047R mutation in PIK3CA was associated with poor PFS of breast cancer (P < 0.05). CONCLUSIONS: Our data and public database research show that the PIK3CA mutation is a significant gene change in breast cancer, and the PIK3CA mutation was associated with a shorter PFS in all, HR + and Her2 + breast cancer patients. This research confirmed the important role of PIK3CA in breast cancer.