title: Correlation between activation of PI3K/AKT/mTOR pathway and prognosis of breast cancer in Chinese women.
abstract: BACKGROUND
  Abnormal activation of PI3K/AKT/mTOR (PAM) pathway, caused by PIK3CA mutation, KRAS mutation, PTEN loss, or AKT1 mutation, is one of the most frequent signaling abnormalities in breast carcinoma. However, distribution and frequencies of mutations in PAM pathway are unclear in breast cancer patients from the mainland of China and the correlation between these mutations and breast cancer outcome remains to be identified.
  
  
  METHODS
  A total of 288 patients with invasive ductal breast cancer were recruited in this study. Mutations in PIK3CA (exons 4, 9 and 20), KRAS (exon 2) and AKT1 (exon 3) were detected using Sanger sequencing. PTEN loss was measured by immunohistochemistry assay. Correlations between these genetic aberrations and clinicopathological features were analyzed.
  
  
  RESULTS
  The frequencies of PIK3CA mutation, KRAS mutation, AKT1 mutation and PTEN loss were 15.6%, 1.8%, 4.4% and 35.3%, respectively. However, except for PTEN loss, which was tied to estrogen receptor (ER) status, these alterations were not associated with other clinicopathological features. Survival analysis demonstrated that PIK3CA mutation, PTEN loss and PAM pathway activation were not associated with disease-free survival (DFS). Subgroup analysis of patients with ER positive tumors revealed that PIK3CA mutation more strongly reduced DFS compared to wild-type PIK3CA (76.2% vs. 54.2%; P = 0.011). PIK3CA mutation was also an independent factor for bad prognosis in ER positive patients.
  
  
  CONCLUSIONS
  AKT1, KRAS and PIK3CA mutations and PTEN loss all exist in women with breast cancer in the mainland China. PIK3CA mutation may contribute to the poor outcome of ER positive breast carcinomas, providing evidence for the combination of PI3K/AKT/mTOR inhibitors and endocrine therapy.
authors: Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Laboratory of Molecular Diagnosis of Cancer, State Key Laboratory of Biotherapy, National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Ling
authors: L
authors: Deng
authors: Department of Thyroid and Breast Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Jie
authors: J
authors: Chen
authors: Laboratory of Molecular Diagnosis of Cancer, State Key Laboratory of Biotherapy, National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Xiao Rong
authors: XR
authors: Zhong
authors: Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Laboratory of Molecular Diagnosis of Cancer, State Key Laboratory of Biotherapy, National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Ting
authors: T
authors: Luo
authors: Laboratory of Molecular Diagnosis of Cancer, State Key Laboratory of Biotherapy, National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Yan Ping
authors: YP
authors: Wang
authors: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Hui Fen
authors: HF
authors: Huang
authors: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Li-Juan
authors: LJ
authors: Yin
authors: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Yan
authors: Y
authors: Qiu
authors: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Hong
authors: H
authors: Bu
authors: Department of Thyroid and Breast Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Qing
authors: Q
authors: Lv
authors: Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Laboratory of Molecular Diagnosis of Cancer, State Key Laboratory of Biotherapy, National Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
authors: Hong
authors: H
authors: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D002681:China; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human; C484760:PIK3CA protein, human