Heritability of Low ER Staining/HER2-Breast Tumors: Are We Missing an Opportunity for Germline Testing?

Genes (Basel). 2020 Dec 8;11(12):1469. doi: 10.3390/genes11121469.


In 2010, the genetic testing criteria was changed to allow women diagnosed ≤ 60 years old with triple negative breast cancer (TNBC) to undergo germline testing. In the same year, estrogen receptor (ER) positivity was defined as having ≥1% ER staining cells. While tumors with 1-10% ER staining cells and HER2 negative (HER2-) status share characteristics with TNBC, the utility of germline testing in women with ER low positive/HER2- (ERLP/HER2-) tumors is not well-understood. To this end, all patients with hormone receptor positive staining cells ≤ 10% and negative HER2 status were identified. Clinical genetic test results were extracted for patients who underwent testing. Panel testing was performed for those women who had genomic DNA available for research purposes. ERLP/HER2-tumors constituted 2.7% of all tumors in the database. Patients did not differ significantly from those with TNBC by age at diagnosis, ethnicity, family history or tumor size, stage or grade (p > 0.05). Mutation frequency did not differ significantly (p = 0.757) between groups (ERLP/HER2- 16.1%; TNBC 16.7%). Hereditary forms of breast cancer were similar in both ERLP/HER2- and TNBC, thus current guidelines may result in the under testing of women with low ER tumors, resulting in missed opportunities to improve patient management.

Keywords: ASCO/CAP guidelines; ER low positive; breast cancer; genetic testing.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Female
  • Germ-Line Mutation*
  • Humans
  • Middle Aged
  • Receptor, ErbB-2* / genetics
  • Receptor, ErbB-2* / metabolism
  • Receptors, Estrogen* / genetics
  • Receptors, Estrogen* / metabolism
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / pathology


  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2