Co-mutation of TP53 and PIK3CA in residual disease after neoadjuvant chemotherapy is associated with poor survival in breast cancer

Purpose The prevalence and clinical relevance of TP53 and PIK3CA mutations in pretreatment breast cancer have been previously reported. However, little is known regarding these mutations in residual tumor tissues after neoadjuvant chemotherapy. Here, we investigated the association between TP53 and PIK3CA mutations in residual disease and survival of breast cancers. Methods TP53 and PIK3CA somatic mutations were examined in 353 post-neoadjuvant chemotherapy residual tumor tissues by Sanger sequencing. Survival curves of patients with TP53 and PIK3CA mutations were compared using the Kaplan–Meier method. Results Fifty-six (15.9%) of the 353 patients carried a TP53 somatic mutation and 79 patients (22.4%) carried a PIK3CA somatic mutation. A total of 18 patients carried co-mutation of TP53 and PIK3CA . Patients with somatic co-mutation were more likely to have high-grade tumors (35.3% vs. 10.6%, P = 0.010), estrogen receptor-negative tumors (55.6% vs. 26.7%, P = 0.009), progesterone receptor-negative tumors (61.1% vs. 30.5%, P = 0.008) and triple-negative tumors (35.3% vs. 13.3%, P = 0.025) compared with non-carriers. More importantly, co-mutation of TP53 and PIK3CA carriers had a significantly worse disease-free survival (DFS) and distant disease-free survival (DDFS) than non-carriers (5-year DFS: 58.0% vs. 83.2%, P