Breast pathology in women with personal and family history of breast cancer, including BRCA1/2 mutation carriers: A model for cancer progression

C. Adem, C. L. Soderberg, C. Reynolds, J. M. Slezak, D. J. Schaid, J. L. Johnson, L. M. Kuntz, K. L. Anderl, T. A. Sellers, L. C. Hartmann, R. B. Jenkins

Research output: Contribution to journalArticle

Abstract

Hereditary breast cancer is related in part to mutations in BRCA1 and BRCA2, tumor suppressor genes thought to be involved in DNA repair. BRCA1/2 mutation carriers (MC) have specific clinical characteristics, such as early age of onset. We hypothesize that the cancers from MC have different progression pathways compared to sporadic cancers and that these differences can be identified by histologic and molecular analyses. Previous studies have described the histologic and molecular phenotype of neoplastic lesions from MC. However, these studies have rarely evaluated preneoplastic lesions. Here, we report the histologic findings in prophylactic mastectomy (PM) and therapeutic mastectomy (TM) specimens from patients that have a personal and familial history of breast carcinoma seen in a large single-institution cohort from Mayo Clinic. Methods: Breast cancer patients with a family history of breast and/or ovarian cancer were screened for BRCA1/2 mutations, and classified as carriers (N=48) or with no mutation detected (N=110). Patients without a family history of breast cancer who underwent TM and PM, matched by age and surgery date, were selected as controls (C) (N=272). All available mastectomy slides were reviewed independently by two pathologists. Available paraffin blocks of neoplastic and preneoplastic lesions were evaluated for MIB-I by immunohistochemistry. Results: There was no difference in the incidence of in situ or invasive cancer between MC and C. Invasive carcinomas from MC were of higher grade and had denser lymphoid infiltrates. However, no pure medullary carcinomas were identified. There was less proliferative fibrocystic change in MC compared to C. Both neoplastic and preneoplastic lesions from MC had higher MIB-I labeling indices compared to similar lesions from C. Conclusion: These histologic data suggest that tumors from MC progress at a faster rate compared to C. Our ongoing genetic studies will help determine if MC and C share similar progression pathways, and potentially have implications for the prevention and treatment of high-risk patients.

Original languageEnglish (US)
Number of pages1
JournalBreast Cancer Research and Treatment
Volume69
Issue number3
StatePublished - Dec 1 2001

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Adem, C., Soderberg, C. L., Reynolds, C., Slezak, J. M., Schaid, D. J., Johnson, J. L., Kuntz, L. M., Anderl, K. L., Sellers, T. A., Hartmann, L. C., & Jenkins, R. B. (2001). Breast pathology in women with personal and family history of breast cancer, including BRCA1/2 mutation carriers: A model for cancer progression. Breast Cancer Research and Treatment, 69(3).