Pathologic features and immunophenotype of estrogen receptor-positive breast cancers in BRCA1 mutation carriers

Am J Surg Pathol. 2012 Oct;36(10):1483-8. doi: 10.1097/PAS.0b013e31825789ed.


Although most breast cancers in BRCA1 mutation carriers are estrogen receptor negative (ER-) with a basal-like phenotype, up to one third are ER positive (ER+). Little is known about the characteristics of this subgroup. To address this, we compared histologic and immunophenotypic features of 60 BRCA1-related ER+ breast cancers with those of 85 BRCA1-related ER- cancers and 174 matched ER+ sporadic cancers. ER+ BRCA1-related cancers were significantly less likely than ER- BRCA1-related cancers to be of pure invasive ductal type (P<0.001) and to be of histologic grade 3 (P<0.001), and less frequently to have a high mitotic rate (P<0.001), pushing (or unknown) margins (P<0.001), a moderate/marked lymphocytic infiltrate (P=0.003), or geographic necrosis/fibrotic focus (P<0.001). In addition, ER+ BRCA1-related cancers less often expressed CK5/6 (P<0.0001), CK14 (P<0.0001), and epidermal growth factor receptor (P<0.0001) and more often expressed progesterone receptor (P<0.0001). In contrast, when compared with ER+ sporadic cancers, ER+ BRCA1-related cancers were significantly more often of invasive ductal type (P=0.005) and of histologic grade 3 (P=0.006), more frequently had a high mitotic rate (P=0.0003), and were more often CK14+ (P=0.03). On unsupervised cluster analysis, some ER+ BRCA1 cancers clustered more closely with sporadic ER+ cancers, whereas others clustered more closely with ER- BRCA1-related cancers. Nuclear expression levels of poly(ADP) ribose polymerase 1 in ER+ BRCA1-related cancers were similar to those in ER- BRCA1-related cancers but significantly higher than in ER+ sporadic cancers. We conclude that ER+ BRCA1-related breast cancers show several morphologic and immunophenotypic differences from ER+ sporadic breast cancers as well as some similarities to ER- BRCA1-related cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / immunology*
  • Carcinoma, Ductal, Breast / pathology*
  • Cluster Analysis
  • Female
  • Fibrosis
  • Heterozygote
  • Humans
  • Immunophenotyping
  • Mutation*
  • Necrosis
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • Tissue Array Analysis


  • BRCA1 Protein
  • BRCA1 protein, human
  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases