title: PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer.
abstract: BACKGROUND
  In vitro evidence suggests that PIK3CA (phosphatidylinositol 3-kinase, catalytic, alpha polypeptide) activation may be associated with altered chemotherapy sensitivity in cancer.
  
  
  METHODS
  Tumor DNA from 140 patients with stage II-III breast cancer undergoing neoadjuvant chemotherapy was sequenced for PIK3CA mutations on exons 1, 9, and 20. Mutation status was correlated with clinical/pathological parameters and chemotherapy response as (a) pathological complete response (pCR) versus residual cancer or (b) quantitative residual cancer burden (RCB) scores, including stratification for estrogen receptor (ER) expression status, type of chemotherapy, and by exons.
  
  
  RESULTS
  Twenty-three patients (16.4%) harbored a PIK3CA mutation, with 12, 11, and 0 mutations located in exons 9, 20, and 1, respectively. PIK3CA exon 9 mutations were more frequent among node-negative (52% versus 25%; P = 0.012) than node-positive tumors, particularly among ER-positive tumors. pCR rates and RCB scores were similar among patients with the wild-type and mutant PIK3CA genes, even after stratification by ER status, chemotherapy regimen (anthracycline versus anthracycline plus paclitaxel), or exon.
  
  
  CONCLUSIONS
  PIK3CA mutations are not associated with altered sensitivity to preoperative anthracycline-based or taxane-based chemotherapies in ER-positive and ER-negative breast tumors. In this study, PIK3CA mutation was associated with a decreased rate of node-positive disease, particularly among ER-positive tumors.
authors: Department of Breast Medical Oncology, University of Texas M, D, Anderson Cancer Center, Houston, TX, USA.
authors: Cornelia
authors: C
authors: Liedtke
authors: Luca
authors: L
authors: Cardone
authors: Attila
authors: A
authors: Tordai
authors: Kai
authors: K
authors: Yan
authors: Henry L
authors: HL
authors: Gomez
authors: Luis J Barajas
authors: LJ
authors: Figureoa
authors: Rebekah E
authors: RE
authors: Hubbard
authors: Vicente
authors: V
authors: Valero
authors: Eduardo A
authors: EA
authors: Souchon
authors: W Fraser
authors: WF
authors: Symmans
authors: Gabriel N
authors: GN
authors: Hortobagyi
authors: Alberto
authors: A
authors: Bardelli
authors: Lajos
authors: L
authors: Pusztai
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; C484760:PIK3CA protein, human