title: The genomic heritage of lymph node metastases: implications for clinical management of patients with breast cancer.
abstract: BACKGROUND
  Metastatic breast cancer is an aggressive disease associated with recurrence and decreased survival. To improve outcomes and develop more effective treatment strategies for patients with breast cancer, it is important to understand the molecular mechanisms underlying metastasis.
  
  
  METHODS
  We used allelic imbalance (AI) to determine the molecular heritage of primary breast tumors and corresponding metastases to the axillary lymph nodes. Paraffin-embedded samples from primary breast tumors and matched metastases (n = 146) were collected from 26 patients with node-positive breast cancer involving multiple axillary nodes. Hierarchical clustering was used to assess overall differences in the patterns of AI, and phylogenetic analysis inferred the molecular heritage of axillary lymph node metastases.
  
  
  RESULTS
  Overall frequencies of AI were significantly higher (P < 0.01) in primary breast tumors (23%) than in lymph node metastases (15%), and there was a high degree of discordance in patterns of AI between primary breast carcinomas and the metastases. Metastatic tumors in the axillary nodes showed different patterns of chromosomal changes, suggesting that multiple molecular mechanisms may govern the process of metastasis in individual patients. Some metastases progressed with few genomic alterations, while others harbored many chromosomal alterations present in the primary tumor.
  
  
  CONCLUSIONS
  The extent of genomic heterogeneity in axillary lymph node metastases differs markedly among individual patients. Genomic diversity may be associated with response to adjuvant therapy, recurrence, and survival, and thus may be important in improving clinical management of breast cancer patients.
authors.affiliation: Clinical Breast Care Project, Windber Research Institute, 620 Seventh Street, Windber, PA 15963, USA.
authors.forename: Tyson E
authors.initials: TE
authors.lastname: Becker
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Ellsworth
authors.forename: Brenda
authors.initials: B
authors.lastname: Deyarmin
authors.forename: Heather L
authors.initials: HL
authors.lastname: Patney
authors.forename: Rick M
authors.initials: RM
authors.lastname: Jordan
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hooke
authors.forename: Craig D
authors.initials: CD
authors.lastname: Shriver
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Ellsworth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance; D001365:Axilla; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics*; D008875:Middle Aged