title: The predictive role of phosphatase and tensin homolog (PTEN) loss, phosphoinositol-3 (PI3) kinase (PIK3CA) mutation, and PI3K pathway activation in sensitivity to trastuzumab in HER2-positive breast cancer: a meta-analysis.
abstract: OBJECTIVE
  Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be related to trastuzumab resistance in in vitro studies; however, this issue in clinical studies is controversial. Therefore, we conducted a meta-analysis to assess the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in HER2-positive breast cancer patients.
  
  
  METHODS
  A computerized search was performed through the PubMed database, the online proceedings of the American Society of Clinical Oncology Annual Meetings, the San Antonio Breast Cancer Symposium and the International St. Gallen Breast Cancer Conference. Ten eligible studies including 1889 cases were identified.
  
  
  RESULTS
  In HER2-positive locally advanced breast cancer patients, neither PTEN loss, PIK3CA mutation nor PI3K activation was associated with the response rate of trastuzumab-based neoadjuvant treatment (PTEN loss: RR = 0.687, 95% CI: 0.439-1.074, P = 0.099; PIK3CA mutation: RR = 1.114, 95% CI: 0.453-2.735, P = 0.814; PI3K activation: RR = 0.787, 95% CI: 0.417-1.484, P = 0.459; RR = 0.772, 95% CI: 0.387-1.539, P = 0.462). In HER2-positive early stage breast cancer patients, PTEN loss was not associated with the disease-free survival (DFS) rate of trastuzumab-based adjuvant treatment (HR = 1.096, 95% CI: 0.706-1.700, P = 0.684). In HER2-positive recurrent or metastatic breast cancer patients, PTEN loss was significantly correlated with poorer efficacy of trastuzumab-based salvage treatment (RR = 0.682, 95% CI: 0.550-0.846, P = 0.000).
  
  
  CONCLUSIONS
  In HER2-positive recurrent or metastatic breast cancer patients PTEN loss might indicate resistance to trastuzumab-based salvage treatment. Due to the small sample size and the considerable heterogeneity in the chemotherapy treatment regimens, further research is needed to clarify the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in neoadjuvant and adjuvant settings.
authors.affiliation: Department of Breast Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yueyao
authors.initials: Y
authors.lastname: Du
authors.forename: Wenjin
authors.initials: W
authors.lastname: Yin
authors.forename: Jinsong
authors.initials: J
authors.lastname: Lu
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016879:Salvage Therapy; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human