PIK3CA Mutation as Potential Poor Prognostic Marker in Asian Female Breast Cancer Patients Who Received Adjuvant Chemotherapy

• Published in: Current oncology (Toronto) Vol. 29; no. 5; pp. 2895 - 2908
• Main Authors: Cho, Yoon Ah, Ko, Seung Yeon, Suh, Yong Joon, Kim, Sanghwa, Park, Jung Ho, Park, Hye-Rim, Seo, Jinwon, Choi, Hyo Geun, Kang, Ho Suk, Lim, Hyun, Park, Ha Young, Kwon, Mi Jung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 19-04-2022; MDPI AG
• Subjects: adjuvant chemotherapy; Asian People - genetics; B7-H1 Antigen - metabolism; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - surgery; c-Met; Chemotherapy, Adjuvant; Class I Phosphatidylinositol 3-Kinases - genetics; Female; Humans; invasive ductal carcinoma; Microsatellite Instability; Middle Aged; Mutation; PD-L1; PIK3CA mutation; Prognosis; invasive ductal carcinoma; mismatch repair proteins; adjuvant chemotherapy; microsatellite instability; PIK3CA mutation; PD-L1; breast cancer; c-Met
• ISSN: 1718-7729; 1198-0052; 1718-7729
• DOI: 10.3390/curroncol29050236

Background: The prognostic relevance of the PIK3CA 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 PIK3CA 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 PIK3CA mutation with PD-L1/c-Met/MMR was explored. Results: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA 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 PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-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: PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.