title: Correlation of breast cancer axillary lymph node metastases with stem cell mutations.
abstract: OBJECTIVE
  Mutations in oncogenes AKT1, HRAS, and PIK3CA in breast cancers result in abnormal PI3K/Akt signaling and tumor proliferation. They occur in ductal carcinoma in situ, in breast cancers, and in breast cancer stem and progenitor cells (BCSCs).
  
  
  OBJECTIVE
  To determine if variability in clinical presentation at diagnosis correlates with PI3K/Akt mutations in BCSCs and provides an early prognostic indicator of increased progression and metastatic potential.
  
  
  METHODS
  Malignant (BCSCs) and benign stem cells were collected from fresh surgical specimens via cell sorting and tested for oncogene mutations in a university hospital surgical oncology research laboratory from 30 invasive ductal breast cancers (stages IA through IIIB).
  
  
  METHODS
  Presence of AKT1, HRAS, and PIK3CA mutations in BCSCs and their correlation with tumor mutations, pathologic tumor stage, tumor histologic grade, tumor hormone receptor status, lymph node metastases, and patient age and condition at the last follow-up contact.
  
  
  RESULTS
  Ten tumors had mutations in their BCSCs. In total, 9 tumors with BCSC mutations and 4 tumors with BCSCs without mutations had associated tumor present in the lymph nodes (P = .001).
  
  
  CONCLUSIONS
  Tumors in which BCSCs have defects in PI3K/Akt signaling are significantly more likely to manifest nodal metastases. These oncogenic defects may be missed by gross molecular testing of the tumor and are markers of more aggressive breast cancer. Molecular profiling of BCSCs may identify patients who would likely benefit from PI3K/Akt inhibitors, which are being tested in clinical trials.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Oregon Health & Science University, Portland.
authors.forename: Cory A
authors.initials: CA
authors.lastname: Donovan
authors.forename: Rodney F
authors.initials: RF
authors.lastname: Pommier
authors.forename: Robynn
authors.initials: R
authors.lastname: Schillace
authors.forename: Steven
authors.initials: S
authors.lastname: O'Neill
authors.forename: Patrick
authors.initials: P
authors.lastname: Muller
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Alabran
authors.forename: Juliana E
authors.initials: JE
authors.lastname: Hansen
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Murphy
authors.forename: Arpana M
authors.initials: AM
authors.lastname: Naik
authors.forename: John T
authors.initials: JT
authors.lastname: Vetto
authors.forename: Suellen J
authors.initials: SJ
authors.lastname: Pommier
mesh_terms: D000367:Age Factors; D001365:Axilla; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D018450:Disease Progression; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013234:Stem Cells / Q000473:pathology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)