Concomitant PIK3CA and TP53 Mutations in Breast Cancer: An Analysis of Clinicopathologic and Mutational Features, Neoadjuvant Therapeutic Response, and Prognosis

Purpose: PIK3CA and TP53 are the most prevalently mutated genes in breast cancer (BC). Previous studies have indicated an association between concomitant PIK3CA/ TP53 mutations and shorter disease-free survival. As its clinical utility remains largely unknown, we aimed to analyze the prognostic and predictive roles of this co-mutation. Methods: We retrospectively analyzed patients who were diagnosed with BC at Guangdong Provincial People's Hospital (GDPH) who underwent next-generation sequencing. The correlation of concomitant PIK3CA/ TP53 mutations with clinicopathological and mutational characteristics, and neoadjuvant systemic therapy (NST) responses was analyzed. The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was used to verify associations between concurrent mutations and survival outcomes. Results: In the GDPH cohort, concomitant PIK3CA/ TP53 mutations were associated with more aggressive phenotypes, including human epidermal growth factor receptor 2 positive status, hormone receptor negative status, high Ki-67 expression, high histological grade, advanced TNM stage, and additional genetic alterations. Co-mutations also portended a worse response to NST, especially taxane-containing regimens, when compared with the TP53 mutant alone (odds ratio, 3.767; 95% confidence interval, 1.205-13.087; p = 0.028). A significant association was observed between concomitant PIK3CA/ TP53 mutations and poor survival outcomes in the METABRIC cohort. Conclusion: Concomitant PIK3CA/ TP53 mutations not only suggested unfavorable features and poor prognosis in BC but also conferred less benefit to NST than TP53 mutations alone.