Prognostic significance of PIK3CA immunoexpression and mutation status in triple-negative breast cancer

Abstract

Aim: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted therapies. This study investigated PIK3CA protein expression in TNBC and, exploratorily, assessed PIK3CA mutations in a subset of tumors with high expression.

Materials and Methods: Sixty-five TNBC cases were retrospectively analyzed. PIK3CA expression was assessed by H-score and grouped for survival analysis as negative versus moderate–high. Six high-expression cases underwent mutation analysis. Associations with clinicopathological parameters, overall and disease-free survival were evaluated using Kaplan–Meier and log-rank tests.

Results: PIK3CA expression was negative in 80.0% (52/65) of cases, while moderate–high expression was observed in 20.0% (13/65). No significant associations were observed between PIK3CA immunohistochemical expression and clinicopathological features (p>0.05). PCR-based mutation analysis was performed on the moderate–high expression subgroup. 33.3% (2/6) of the tested high-expression cases harbored PIK3CA mutations. All deaths occurred in the negative-expression group; overall survival was significantly better in the moderate–high expression group (p = 0.043).  However, no death events were observed in the moderate–high subgroup (n = 13), and this finding should be interpreted cautiously because of the low number of events. No significant difference in disease-free survival was found between groups (p = 0.588).

Conclusion: PIK3CA protein expression was not associated with conventional clinicopathological prognostic parameters in TNBC. Nevertheless, moderate–high PIK3CA expression was associated with better overall survival, indicating a hypothesis-generating rather than an independent prognostic effect. Moreover, despite the absence of significant differences at the immunohistochemical level, PIK3CA mutations were detected by PCR in a limited subset of high-expression cases, highlighting a potential discordance between protein expression and molecular alterations. These findings warrant validation in larger, multicenter studies.