title: Favorable prognostic impact in loss of TP53 and PIK3CA mutations after neoadjuvant chemotherapy in breast cancer.
abstract: We investigated the loss of somatic mutations in TP53 and PIK3CA in breast cancer tissue after neoadjuvant chemotherapy (NCT) and the clinical relevance of the observed mutation profiles. Samples were derived from three cohorts: Cohort 1 consisting of 206 patients undergoing NCT with matched pre- and postchemotherapy tumor tissues; Cohort 2 consisting of 158 additional patients undergoing NCT; and Cohort 3, consisting of 81 patients undergoing chemotherapy with prechemotherapy tumor tissues. In the first cohort, somatic mutations in TP53 or PIK3CA were identified in 24.8% of the pre-NCT tumor samples but in only 12.1% of the post-NCT tumor samples (P < 0.001). Patients with initial TP53 and PIK3CA mutations who became negative for the mutations after NCT had a higher Miller-Payne score (P = 0.008), improved disease-free survival, and improved overall survival than those with no change or the opposite change. The association of loss of mutations in TP53 and PIK3CA and improved survival was successfully validated in the second cohort. In addition, 28.4% of the tumors showed intratumoral heterogeneity of somatic mutations in TP53 or PIK3CA, whereas 71.6% were homogeneous, either with or without the mutations. Our data reveal the novel concept that chemotherapy may reduce mutation frequency in patients with breast cancer. Furthermore, the loss of somatic mutations in TP53 and PIK3CA may be translated to biomarkers for prognosis via further verification, which may optimize the choice of sequential therapy and improve patient survival.
authors.affiliation: Authors' Affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Jiang
authors.affiliation: Authors' Affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China zhimingshao@yahoo.com yukd@shca.org.cn.
authors.forename: Ke-Da
authors.initials: KD
authors.lastname: Yu
authors.affiliation: Authors' Affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bao
authors.affiliation: Authors' Affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Peng
authors.affiliation: Authors' Affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China zhimingshao@yahoo.com yukd@shca.org.cn.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D016190:Carboplatin / Q000627:therapeutic use; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016190:Carboplatin; D058534:Class I Phosphatidylinositol 3-Kinases; D017239:Paclitaxel; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011982:Receptors, Prostaglandin; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human