Pattern of Somatic Mutations in the PIK3CA Oncogene and Their Role as a Potential Prognostic Biomarker in Breast...

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit-alpha (PIK3CA) oncogene is one of the most frequently mutated oncogenes in breast cancer, with mutations influencing prognosis and therapeutic response. This study aimed to determine the pattern of hotspot PIK3CA mutations and assess their association with clinicopathological parameters and relapse-free survival (RFS) among Sri Lankan breast cancer patients.

A qPCR-based genetic analysis was performed on DNA from formalin-fixed, paraffin-embedded (FFPE) tissue samples of 63 clinically diagnosed female Sri Lankan breast cancer patients, using the QClamp® PIK3CA Mutation Detection Test to detect hotspot mutations in PIK3CA (i.e., H1047R, E545K, E542K), followed by statistical analysis. Patient samples and clinical data were fully anonymized, with no identifying information available to the authors at any point during the study.

Somatic missense PIK3CA mutations H1047R and E542K were detected in 17.46% of the cohort. The E545K mutation was not detected. The observed mutations were associated with an increased risk of lymph node (LN) metastasis (p=0.036, OR 9.60) and reduced recurrence-free survival (RFS) (p<0.001, HR 26.19). Patients with a high Ki67 index (p=0.029, HR 79.69) and LN-positive status (p=0.026, HR 123.94) also showed worse outcomes. In addition, the combination of all three factors- presence of a PIK3CA mutation, LN metastasis, and a high Ki67 index- was associated with reduced RFS (p<0.001).

Despite being a pilot study, the findings indicate that PIK3CA mutations are associated with adverse prognostic outcomes in Sri Lankan breast cancer patients. These results demonstrate the potential utility of PIK3CA testing and PI3K-targeted therapy in clinical management in Sri Lankan, pending validation in larger cohorts.