Xinyi Chen1, Yonghai Guo1, Tao Ouyang1, Jinfeng Li1, Tianfeng Wang1, Zhaoqing Fan1, Tie Fan1, Benyao Lin1, Ye Xu2, Yuntao Xie3. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Beijing Cancer Hospital and Institute, Peking University Cancer Hospital, Beijing, 100142, People's Republic of China. 2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Beijing Cancer Hospital and Institute, Peking University Cancer Hospital, Beijing, 100142, People's Republic of China. xuye@bjmu.edu.cn. 3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, Beijing Cancer Hospital and Institute, Peking University Cancer Hospital, Beijing, 100142, People's Republic of China. zlxyt2@bjmu.edu.cn.
Abstract
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 < 0.001; 5-year DDFS: 70.3% vs. 86.4%, P = 0.024). Furthermore, in multivariate regression analysis, TP53 and PIK3CA co-mutation carriers showed a significantly worse DFS (adjusted hazard ratio = 3.70; 95% confidence interval, 1.79-7.63; P < 0.001). CONCLUSIONS: Patients with somatic co-mutation of TP53 and PIK3CA were associated with unfavorable survival compared with non-carriers. Co-mutation of TP53 and PIK3CA could be used as a potential prognosis marker in post-neoadjuvant chemotherapy breast cancer patients.
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 < 0.001; 5-year DDFS: 70.3% vs. 86.4%, P = 0.024). Furthermore, in multivariate regression analysis, TP53 and PIK3CA co-mutation carriers showed a significantly worse DFS (adjusted hazard ratio = 3.70; 95% confidence interval, 1.79-7.63; P < 0.001). CONCLUSIONS:Patients with somatic co-mutation of TP53 and PIK3CA were associated with unfavorable survival compared with non-carriers. Co-mutation of TP53 and PIK3CA could be used as a potential prognosis marker in post-neoadjuvant chemotherapy breast cancerpatients.
Entities:
Keywords:
Breast cancer; PIK3CA; Post-neoadjuvant chemotherapy; Survival; TP53