title: High prevalence of preinvasive lesions adjacent to BRCA1/2-associated breast cancers.
abstract: Mutations in BRCA1 and BRCA2 increase a woman's lifetime risk of developing breast cancer by 43% to 84%. It was originally postulated that BRCA1/2-associated breast cancers develop more rapidly than sporadic cancers and may lack preinvasive lesions. More recent studies have found preinvasive lesions in prophylactic mastectomy specimens from mutation carriers; however, there is little information on the presence of preinvasive lesions in tissue adjacent to breast cancers. Our aim is to investigate the role of preinvasive lesions in BRCA-associated breast carcinogenesis. We retrospectively compared BRCA1/2-associated breast cancers and sporadic breast cancers for the prevalence of preinvasive lesions [ductal carcinoma in situ (DCIS), lobular carcinoma in situ, and atypical lobular hyperplasia] in tissue adjacent to invasive breast cancers. Pathology was reviewed for 73 BRCA1/2-associated tumors from patients with breast cancer. We selected 146 patients with mutation-negative breast cancer as age-matched controls. Among the BRCA1/2-associated breast cancers, 59% had at least one associated preinvasive lesion compared with 75% of controls. Preinvasive lesions were more prevalent in BRCA2 mutation carriers than in BRCA1 mutation carriers (70% versus 52%, respectively). The most common preinvasive lesion in both groups was DCIS; 56% of BRCA1/2-associated breast cancers and 71% of the sporadic breast cancers had adjacent intraductal disease, respectively. Preinvasive lesions, most notably DCIS, are common in BRCA1/2-associated breast cancers. These findings suggest that BRCA1/2-associated breast cancers progress through the same intermediate steps as sporadic breast cancers, and that DCIS should be considered as a part of the BRCA1/2 tumor spectrum.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. barun@mdanderson.org
authors.forename: Banu
authors.initials: B
authors.lastname: Arun
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Vogel
authors.forename: Adriana
authors.initials: A
authors.lastname: Lopez
authors.forename: Mike
authors.initials: M
authors.lastname: Hernandez
authors.forename: Deann
authors.initials: D
authors.lastname: Atchley
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Broglio
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: Henry
authors.initials: H
authors.lastname: Kuerer
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Constance T
authors.initials: CT
authors.lastname: Albarracin
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology; D018276:Carcinoma, Medullary / Q000235:genetics / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein