title: Association of PIK3CA Mutation Status before and after Neoadjuvant Chemotherapy with Response to Chemotherapy in Women with Breast Cancer.
abstract: OBJECTIVE
  The association between PIK3CA mutations and response to neoadjuvant chemotherapy in women with primary breast cancer is not fully elucidated.
  
  
  METHODS
  PIK3CA mutations in breast cancer tissues that were taken prior to the initiation of neoadjuvant chemotherapy were identified in 729 operable primary breast cancer patients who received neoadjuvant chemotherapy. Among these, the PIK3CA mutations were also reassessed in tumor tissues procured following operation in 102 patients after completion of neoadjuvant chemotherapy.
  
  
  RESULTS
  A total of 206 out of 729 (28.3%) patients had PIK3CA mutations, and 19.5% of patients (142/729) in this cohort achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy. Patients with PIK3CA mutations exhibited a lower pCR rate than did those with wild-type (14.6% vs. 21.4%, P = 0.035). No significant differences in disease-free survival (DFS) or distant disease-free survival (DDFS) were observed between PIK3CA mutant and wild-type in the entire study population. Among the 102 patients with PIK3CA mutation statuses available before and after neoadjuvant chemotherapy, 24 patients (23.5%) had PIK3CA mutations before neoadjuvant chemotherapy. Of these 24 patients, 15 patients retained their initial PIK3CA mutations and 9 patients lost their initial mutations after neoadjuvant chemotherapy. Patients who retained the initial mutations after neoadjuvant chemotherapy (n = 15) had a worse DDFS than the remaining patients (n = 87) in this subgroup [unadjusted HR, 2.34; 95% confidence interval (CI), 0.98-5.62; P = 0.050].
  
  
  CONCLUSIONS
  Patients with PIK3CA mutations are less likely to respond to neoadjuvant chemotherapy. Patients who retain their initial PIK3CA mutations after neoadjuvant chemotherapy have an unfavorable survival.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Jiuan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ouyang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Tie
authors.initials: T
authors.lastname: Fan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Benyao
authors.initials: B
authors.lastname: Lin
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Breast Center, and Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China. zlxyt2@bjmu.edu.cn.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D062005:Biopsy, Large-Core Needle; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D009154:Mutation; D059645:Mutation Rate; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human