title: Risk factors for local recurrence after breast-conserving therapy for invasive carcinomas: a case-control study of histological factors and alterations in oncogene expression.
abstract: OBJECTIVE
  Many studies have focused on histological risk factors for local recurrence (LR) after breast-conserving therapy (BCT). In addition to histological factors, we studied alterations in the expression of various proteins in relation to LR using a case-control approach.
  
  
  METHODS
  Ninety-nine LR occurred in a patient cohort of 1,481 tumors treated with BCT. These patients were randomly matched, each with two controls. Matching was performed for age group (< or = 50 and > 50 years), pN stage, and follow-up time. Histology slides were reviewed. Immunohistochemical staining was performed for the following proteins: bcl-2, CD31, cyclin D1, E-cadherin, EGF receptor, ER, PR, Ki-67, c-erbB2/neu, and p53. Statistical analyses were performed using conditional logistic regression.
  
  
  RESULTS
  Sixty-six cases and 139 controls with invasive carcinoma remained for analysis. The following variables were significant risk factors for LR: young age (p = 0.006), high nuclear grade (p = 0.04), high mitotic count (p = 0.03), extensive DCIS around the tumor (p = 0.02) but not within the tumor, poorly differentiated type of DCIS (p = 0.03), > 20% ki-67 positive cells (p = 0.006), and PR negativity (p = 0.03). When the analysis was performed for patients < or = and > 50 years, these risk factors were found in the older patients, but not in the younger patients.
  
  
  CONCLUSIONS
  High mitotic count and Ki-67 positivity are risk factors for LR. EDCIS surrounding the invasive tumor is a risk factor for LR, especially when of poorly differentiated type. Age is an important risk factor for LR independent of other risk factors, including alterations in oncogene expression.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, The Netherlands.
authors.forename: P H
authors.initials: PH
authors.lastname: Elkhuizen
authors.forename: A C
authors.initials: AC
authors.lastname: Voogd
authors.forename: L C
authors.initials: LC
authors.lastname: van den Broek
authors.forename: I T
authors.initials: IT
authors.lastname: Tan
authors.forename: H C
authors.initials: HC
authors.lastname: van Houwelingen
authors.forename: J W
authors.initials: JW
authors.lastname: Leer
authors.forename: M J
authors.initials: MJ
authors.lastname: van de Vijver
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D009363:Neoplasm Proteins