title: PIK3CA mutation associates with improved outcome in breast cancer.
abstract: OBJECTIVE
  In breast cancer, somatic mutations in the PIK3CA gene are common. The prognostic implication of these activating mutations remains uncertain as moderately sized studies have yielded variable outcomes. Our aim was to determine the prognostic implications of PIK3CA mutations in breast cancer.
  
  
  METHODS
  Archival formalin-fixed paraffin-embedded primary breast tumors, from 590 patients selected for known vital status with a median follow-up of 12.8 years and a tumor >1 cm, were genotyped for PIK3CA mutations. Mutation rates and associations between mutation site and clinicopathologic characteristics were assessed. Progression-free survival, overall survival, and breast cancer-specific survival were examined using Kaplan-Meier or competing risk methodology.
  
  
  RESULTS
  PIK3CA mutation is identified in 32.5% of breast cancers. PIK3CA mutation significantly associates with older age at diagnosis, hormone receptor positivity, HER2 negativity, lower tumor grade and stage, and lymph node negativity. Patients with PIK3CA mutated tumors have significant improvement in overall survival (P = 0.03) and breast cancer-specific survival (P = 0.004). Analysis for PIK3CA mutation site-specific associations reveals that the H1047R kinase domain mutation highly associates with node negativity (P = 0.007), whereas helical domain hotspot mutations associate with older age at diagnosis (P = 0.004).
  
  
  CONCLUSIONS
  This study defines the positive prognostic significance of PIK3CA mutations. This work is clinically relevant, as it will significantly affect the design of clinical trials planned for phosphatidylinositol 3-kinase-targeted therapy. Future work may define a population of older age breast cancer patients in whom therapy can be minimized.
authors: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors: Kevin
authors: K
authors: Kalinsky
authors: Lindsay M
authors: LM
authors: Jacks
authors: Adriana
authors: A
authors: Heguy
authors: Sujata
authors: S
authors: Patil
authors: Marija
authors: M
authors: Drobnjak
authors: Umeshkumar K
authors: UK
authors: Bhanot
authors: Cyrus V
authors: CV
authors: Hedvat
authors: Tiffany A
authors: TA
authors: Traina
authors: David
authors: D
authors: Solit
authors: William
authors: W
authors: Gerald
authors: Mary Ellen
authors: ME
authors: Moynahan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis / Q000379:methods; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C484760:PIK3CA protein, human