title: High prevalence of premalignant lesions in prophylactically removed breasts from women at hereditary risk for breast cancer.
abstract: OBJECTIVE
  Women with a hereditary predisposition for breast cancer have an extremely high risk of developing invasive breast carcinoma, and many women consider prophylactic mastectomy to avoid this risk. The use of prophylactic mastectomy is still debated. Identification of frequent premalignant lesions in mastectomy specimens would support the preventive concept of prophylactic mastectomy.
  
  
  METHODS
  We performed a prospective study of breast specimens from 67 women at extremely high genetic risk of breast cancer, with or without previous breast cancer, who were undergoing prophylactic mastectomy (66% were carriers of a BRCA1 or BRCA2 mutation). Breast specimens were studied by radiographic and macroscopic examination of 5-mm tissue slices, with subsequent histology of suspicious lesions and random samples from each quadrant of the breast and the nipple area.
  
  
  RESULTS
  In 57% of the women, one or more different types of high-risk histopathologic lesions were present: 37% atypical lobular hyperplasia, 39% atypical ductal hyperplasia, 25% lobular carcinoma-in-situ, and 15% ductal carcinoma-in-situ. A 4-mm invasive ductal carcinoma was found in one woman with ductal carcinoma-in-situ. None of these lesions was detected at palpation or mammography, which were performed before the mastectomy. The presence of high-risk lesions was independently related to age older than 40 years (odds ratio, 6.6; P =.01) and to bilateral oophorectomy before prophylactic mastectomy (odds ratio, 0.2; P = 0.02).
  
  
  CONCLUSIONS
  Many women at high risk of hereditary breast cancer develop high-risk histopathologic lesions, especially after the age of 40 years. Surveillance does not detect such high-risk histopathologic lesions.
authors.affiliation: Hereditary Cancer Clinic, Department of Human Genetics, University Medical Center Nijmegen, The Netherlands. n.hoogerbrugge@antrg.azn.nl
authors.forename: N
authors.initials: N
authors.lastname: Hoogerbrugge
authors.forename: P
authors.initials: P
authors.lastname: Bult
authors.forename: L M
authors.initials: LM
authors.lastname: de Widt-Levert
authors.forename: L V
authors.initials: LV
authors.lastname: Beex
authors.forename: L A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: M J L
authors.initials: MJ
authors.lastname: Ligtenberg
authors.forename: L F
authors.initials: LF
authors.lastname: Massuger
authors.forename: C
authors.initials: C
authors.lastname: Boetes
authors.forename: P
authors.initials: P
authors.lastname: Manders
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
mesh_terms: D000328:Adult; D017677:Age Distribution; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D002278:Carcinoma in Situ / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006965:Hyperplasia / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D008408:Mastectomy; D008875:Middle Aged; D015999:Multivariate Analysis; D011230:Precancerous Conditions / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D015995:Prevalence; D011446:Prospective Studies; D012372:ROC Curve; D012306:Risk