title: Outcome impact of PIK3CA mutations in HER2-positive breast cancer patients treated with trastuzumab.
abstract: BACKGROUND
  Phosphatidylinositol 3-kinase (PI3K) pathway activation has been suggested to negatively influence response to anti-HER2 therapy in breast cancer patients. The present study focused on mutations of the PIK3CA gene, encoding one of the two PI3K subunits.
  
  
  METHODS
  PIK3CA mutations were assessed by direct sequencing in 80 HER2-positive patients treated with 1 year of trastuzumab. All patients preoperatively received four cycles of anthracycline-based chemotherapy, followed by four cycles of docetaxel and 1 year of trastuzumab, starting either before surgery with the first cycle of docetaxel and continuing after surgery (neoadjuvant trastuzumab arm, n=43), or only after surgery (adjuvant trastuzumab arm, n=37).
  
  
  RESULTS
  PIK3CA mutations were found in 17 tumours (21.3%). Better disease-free survival (DFS) was observed in patients with PIK3CA wild-type compared with mutated tumours (P=0.0063). By combining PIK3CA status and treatment arms, four separate prognostic groups with significantly different DFS (P=0.0013) were identified.
  
  
  CONCLUSIONS
  These results confirm that the outcome of HER2-positive patients treated with trastuzumab is significantly worse in patients with PIK3CA-mutated compared with wild-type tumours.
authors.affiliation: Oncogenetic Laboratory, Institut Curie, Hospital René Huguenin, 35 Rue Dailly, 92210 Saint-Cloud, France.
authors.forename: M
authors.initials: M
authors.lastname: Cizkova
authors.forename: M-E
authors.initials: ME
authors.lastname: Dujaric
authors.forename: J
authors.initials: J
authors.lastname: Lehmann-Che
authors.forename: V
authors.initials: V
authors.lastname: Scott
authors.forename: O
authors.initials: O
authors.lastname: Tembo
authors.forename: B
authors.initials: B
authors.lastname: Asselain
authors.forename: J-Y
authors.initials: JY
authors.lastname: Pierga
authors.forename: M
authors.initials: M
authors.lastname: Marty
authors.forename: P
authors.initials: P
authors.lastname: de Cremoux
authors.forename: F
authors.initials: F
authors.lastname: Spyratos
authors.forename: I
authors.initials: I
authors.lastname: Bieche
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D043823:Taxoids / Q000627:therapeutic use; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D000077143:Docetaxel; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human