title: PIK3CA mutation impact on survival in breast cancer patients and in ERα, PR and ERBB2-based subgroups.
abstract: BACKGROUND
  PIK3CA is the oncogene showing the highest frequency of gain-of-function mutations in breast cancer, but the prognostic value of PIK3CA mutation status is controversial.
  
  
  METHODS
  We investigated the prognostic significance of PIK3CA mutation status in a series of 452 patients with unilateral invasive primary breast cancer and known long-term outcome (median follow-up 10 years).
  
  
  RESULTS
  PIK3CA mutations were identified in 151 tumors (33.4%). The frequency of PIK3CA mutations differed markedly according to hormone receptor (estrogen receptor alpha [ERα] and progesterone receptor [PR]) and ERBB2 status, ranging from 12.5% in the triple-negative subgroup (ER-/PR-/ERBB2-) to 41.1% in the HR+/ERBB2- subgroup. PIK3CA mutation was associated with significantly longer metastasis-free survival in the overall population (P = 0.0056), and especially in the PR-positive and ERBB2-positive subgroups. In Cox multivariate regression analysis, the prognostic significance of PIK3CA mutation status persisted only in the ERBB2-positive subgroup.
  
  
  CONCLUSIONS
  This study confirms the high prevalence of PIK3CA mutations in breast cancer. PIK3CA mutation is an emerging tumor marker which might become used in treatment-choosing process. The independent prognostic value of PIK3CA mutation status in ERBB2-positive breast cancer patients should be now confirmed in larger series of patients included in randomized prospective ERBB2-based clinical trials.
authors.affiliation: Laboratoire d'Oncogénétique, Institut Curie, Hôpital René Huguenin, 35 Rue Dailly, Saint-Cloud, F-92210, France. ivan.bieche@curie.net
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cizkova
authors.forename: Aurélie
authors.initials: A
authors.lastname: Susini
authors.forename: Sophie
authors.initials: S
authors.lastname: Vacher
authors.forename: Géraldine
authors.initials: G
authors.lastname: Cizeron-Clairac
authors.forename: Catherine
authors.initials: C
authors.lastname: Andrieu
authors.forename: Keltouma
authors.initials: K
authors.lastname: Driouch
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Fourme
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D020125:Mutation, Missense; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D047628:Estrogen Receptor alpha; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C506487:ESR1 protein, human; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human