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Background: The prognostic relevance of the <i>PIK3CA</i> mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy. Methods: We analyzed <i>PIK3CA</i> mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the <i>PIK3CA</i> mutation with PD-L1/c-Met/MMR was explored. Results: The PNA clamp-mediated assay was able to detect the <i>PIK3CA</i> mutation in 1% of the mutant population in the cell line validation. Using this method, the <i>PIK3CA</i> mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The <i>PIK3CA</i> mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the <i>PIK3CA</i>-mutated tumors showed poorer RFS than the <i>PIK3CA</i>-wildtype within the c-Met-positive, MSS, triple-negative, or age onset <50 years subgroups, which showed a similar trend of association in TCGA data. Conclusions: <i>PIK3CA</i> mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.