Concordance of breast cancer biomarker status between routine immunohistochemistry/in situ hybridization and Oncotype DX qRT-PCR with investigation of discordance, a study of 591 cases

Hum Pathol. 2020 Oct:104:54-65. doi: 10.1016/j.humpath.2020.07.022. Epub 2020 Aug 3.

Abstract

Patients with estrogen receptor (ER)+/human epidermal growth factor receptor (HER)2-, lymph node- breast cancer with high recurrence risk benefit from adjuvant chemotherapy in addition to hormonal therapy. This study compares ER, progesterone receptor (PR), and HER2 status between routine immunohistochemistry (IHC)/in situ hybridization (ISH) and Oncotype DX (ODX) in 591 cases. ODX recurrence score (RS) and clinicopathologic features were compared between ER/PR-concordant and discordant cases. Hematoxylin and eosin (H&E) slides from ER discordant cases were reexamined. Concordance was high between ODX and IHC for ER status (580/591, 98.1%) and moderate for PR status (512/591, 86.6%). All 11 ER discordant cases were ER+ by IHC but ER- by ODX and high risk by ODX. Histologically, all of these cases were grade III invasive ductal carcinoma (IDC), except one case diagnosed as IDC with apocrine features. Although this case was grade I and ER/PR+ by IHC, this patient received chemotherapy because of high RS. Of 79 PR discordant cases, 60 were PR+ by IHC but PR- by ODX. Five hundred eighty-four cases had available HER2 data, with high negative agreement (580/582, 99.7%). However, both HER2+ cases by ISH were HER2- by ODX. Mean RS was higher for ER discordant than concordant cases (48.0 versus 17.1, P < 0.0001) and for PR discordant (IHC+/ODX-) than concordant cases (27.2 versus 16.7, P < 0.0001) with no significant differences in recurrence or metastasis. Overall, detection was more sensitive by IHC, and high RS of discordant cases suggests possible risk overestimation. Therapeutic decisions for discordant cases should continue to be based on clinicopathologic correlation and not oncotype alone.

Keywords: Breast cancer; Concordance; Estrogen receptor; HER2; Immunohistochemistry; Oncotype DX; Progesterone receptor.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Clinical Decision-Making
  • Female
  • Gene Expression Profiling*
  • Humans
  • Immunohistochemistry*
  • In Situ Hybridization*
  • Middle Aged
  • Neoplasm Grading
  • Predictive Value of Tests
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / analysis
  • Receptors, Progesterone / genetics
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction*
  • Risk Assessment
  • Risk Factors
  • Transcriptome
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2