title: Molecular evidence demonstrating local treatment failure is the source of distant metastases in some patients treated for breast cancer.
abstract: OBJECTIVE
  To examine the clonality relationships among initial invasive breast carcinoma (IBC), ipsilateral breast failure (IBF), and distant metastasis (DM) to determine the effect of local tumor recurrence on the development of DMs.
  
  
  METHODS
  A total of 18 patients treated with breast-conserving therapy who developed an IBF followed by DMs were studied using a 20 informative-marker, polymerase chain reaction-based allelic imbalance clonality assay.
  
  
  RESULTS
  Four relationships were identified. First, in 7 cases, the IBF and DMs were clonally related to the initial IBC as one progressively genetic unstable process. Second, in 3 cases, the IBF and DMs were each clonally related to the IBC but clonally distinct from each other. Third, in 3 cases, the IBC and the IBF were clonally related and the DMs were clonally related to the IBFs, with a weak relationship to the initial IBC. Finally, in 5 cases, the IBF was clonally distinct from the initial IBC (new second primary) and the DMs were clonally related to the IBF and clonally distinct from the initial IBC.
  
  
  CONCLUSIONS
  These findings provide molecular evidence demonstrating that some DMs can directly develop from IBFs and support the importance of local tumor control in the overall treatment of breast cancer patients.
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48072, USA. fvicini@beaumont.edu
authors.forename: Frank A
authors.initials: FA
authors.lastname: Vicini
authors.forename: Neal S
authors.initials: NS
authors.lastname: Goldstein
authors.forename: Michelle
authors.initials: M
authors.lastname: Wallace
authors.forename: Larry
authors.initials: L
authors.lastname: Kestin
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D002277:Carcinoma / Q000097:blood / Q000556:secondary* / Q000628:therapy*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008875:Middle Aged; D017211:Treatment Failure
chemical_list: D014408:Biomarkers, Tumor