Pathology of BRCA1- and BRCA2-associated Breast Cancers: Known and Less Known Connections

Clin Breast Cancer. 2020 Apr;20(2):152-159. doi: 10.1016/j.clbc.2019.08.003. Epub 2019 Aug 22.

Abstract

Introduction: BRCA1/BRCA2 mutation carriers indefinitely comprise a distinct group of patients with breast cancer (BC), with their tumors displaying specific pathologic characteristics. Although these connections are known, they are not fully elucidated. We therefore sought to investigate the clinicopathologic characteristics and overall survival of Greek patients with BC carrying BRCA1/BRCA2 mutations.

Patients and methods: Greek patients with BC diagnosed between 1999 and 2016, fulfilling the National Comprehensive Cancer Network criteria for genetic testing, were analyzed for BRCA1/BRCA2 mutations by Sanger sequencing or by a 94-gene panel. Medical records and pathology reports were retrospectively reviewed to retrieve patient and tumor baseline characteristics. Potential associations with mutation status were assessed using the Fisher exact, Pearson χ2, and Mann-Whitney tests.

Results: Of 2096 selected patients with BC, we identified 297 (14.2%) BRCA1 and 88 (4.2%) BRCA2 carriers. The mean age at BC diagnosis was 40 and 42.6 years, respectively (P = .02). Tumor histologic subtypes in BRCA1 and BRCA2 carriers were predominantly ductal (79%) followed by medullary (10%), and ductal (72%) followed by lobular (15%), respectively. A significantly higher percentage of BRCA2 tumors were human epidermal growth factor receptor 2-positive, compared with BRCA1 tumors (21.7% vs. 5.8%; P < .001). Second primary cancer diagnosis was more frequent in BRCA1 compared with BRCA2 mutation carriers (36.2% vs. 10.7%; P < .001), whereas there was no difference in 15-year overall survival (hazard ratio, 0.92; 95% confidence interval, 0.48-1.83; P = .804) between the 2 groups.

Conclusions: These data confirm established observations in the pathology of BRCA-related tumors and provide further insight on the association of rare histologic entities with mutations in these genes, which can be clinically beneficial.

Keywords: HER2; Hereditary breast cancer; Mutations; Overall survival; TNBC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast / pathology*
  • Breast / surgery
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / therapy
  • Carcinoma, Lobular / genetics*
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / pathology
  • Carcinoma, Lobular / therapy
  • Carcinoma, Medullary / genetics*
  • Carcinoma, Medullary / mortality
  • Carcinoma, Medullary / pathology
  • Carcinoma, Medullary / therapy
  • Chemotherapy, Adjuvant
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genetic Testing / statistics & numerical data
  • Greece
  • Heterozygote
  • Humans
  • Kaplan-Meier Estimate
  • Mastectomy
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Neoplasms, Second Primary / genetics*
  • Neoplasms, Second Primary / mortality
  • Neoplasms, Second Primary / pathology
  • Neoplasms, Second Primary / therapy
  • Radiotherapy, Adjuvant
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human