High prevalence of preinvasive lesions adjacent to BRCA1/2-associated breast cancers

Cancer Prev Res (Phila). 2009 Feb;2(2):122-7. doi: 10.1158/1940-6207.CAPR-08-0050. Epub 2009 Jan 27.

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.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma in Situ / genetics*
  • Carcinoma in Situ / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / pathology
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / pathology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Middle Aged
  • Mutation / genetics*
  • Retrospective Studies

Substances

  • BRCA1 Protein
  • BRCA2 Protein