High incidence of germline BRCA mutation in patients with ER low-positive/PR low-positive/HER-2 neu negative tumors

Cancer. 2015 Oct 1;121(19):3422-7. doi: 10.1002/cncr.29572. Epub 2015 Aug 17.


Background: The 2015 National Comprehensive Cancer Network guidelines recommend that genetic counseling and germline BRCA mutation testing be offered to women under age 60 with triple-negative breast cancer (TNBC). As a result of the 2010 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for breast cancer, patients with breast cancers that are estrogen receptor (ER) or progesterone receptor (PR) low-positive (1%-9% on immunohistochemistry) are no longer strictly considered to have TNBC and may not be referred for genetic counseling. However, the incidence of BRCA mutation in patients with hormone receptor (HR) low-positive breast cancers remains unknown, and current ASCO/CAP guidelines may result in undertesting for BRCA mutations.

Methods: A prospectively maintained research database of breast cancer patients evaluated at The University of Texas MD Anderson Cancer Center between 2004 and 2014 was reviewed; 314 patients were identified with HER2/neu-negative breast cancers expressing ER and PR <10% with known BRCA mutation status.

Results: Three hundred fourteen patients had breast cancers expressing ER and PR <10%; 238 (75.8%) had HR-negative cancers (<1% ER and PR), and 76 (24.2%) had HR-low-positive cancers (1%-9% ER and/or PR). Among patients with HR-negative tumors, 86 of 238 (36.1%) had a BRCA1/2 mutation, whereas in the HR-low-positive group, 30 of 76 (39.5%) had a BRCA1/2 mutation. In multivariate analysis, HR status (<1% vs 1%-9%) was not significantly associated with BRCA1/2 mutations.

Conclusions: The incidence of BRCA1/2 mutations is similar in patients with HR-low-positive breast cancer and patients with HR-negative breast cancer. Genetic counseling and BRCA testing should be offered to patients under age 60 who have HR-low-positive breast cancers. Cancer 2015;121:3435-43. © 2015 American Cancer Society.

Keywords: BRCA1 gene; BRCA2 gene; genetic counseling; immunohistochemistry; triple-negative breast neoplasms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cohort Studies
  • Female
  • Genes, BRCA2
  • Genetic Counseling
  • Germ-Line Mutation
  • Humans
  • Incidence
  • Prospective Studies
  • Receptor, ErbB-2 / genetics*


  • Receptor, ErbB-2