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Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium.

Publication ,  Journal Article
Allott, EH; Cohen, SM; Geradts, J; Sun, X; Khoury, T; Bshara, W; Zirpoli, GR; Miller, CR; Hwang, H; Thorne, LB; O'Connor, S; Tse, C-K; Hu, Z ...
Published in: Cancer Epidemiol Biomarkers Prev
March 2016

BACKGROUND: Classification of breast cancer into intrinsic subtypes has clinical and epidemiologic importance. To examine accuracy of IHC-based methods for identifying intrinsic subtypes, a three-biomarker IHC panel was compared with the clinical record and RNA-based intrinsic (PAM50) subtypes. METHODS: Automated scoring of estrogen receptor (ER), progesterone receptor (PR), and HER2 was performed on IHC-stained tissue microarrays comprising 1,920 cases from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Multiple cores (1-6/case) were collapsed to classify cases, and automated scoring was compared with the clinical record and to RNA-based subtyping. RESULTS: Automated analysis of the three-biomarker IHC panel produced high agreement with the clinical record (93% for ER and HER2, and 88% for PR). Cases with low tumor cellularity and smaller core size had reduced agreement with the clinical record. IHC-based definitions had high agreement with the clinical record regardless of hormone receptor positivity threshold (1% vs. 10%), but a 10% threshold produced highest agreement with RNA-based intrinsic subtypes. Using a 10% threshold, IHC-based definitions identified the basal-like intrinsic subtype with high sensitivity (86%), although sensitivity was lower for luminal A, luminal B, and HER2-enriched subtypes (76%, 40%, and 37%, respectively). CONCLUSION: Three-biomarker IHC-based subtyping has reasonable accuracy for distinguishing basal-like from nonbasal-like, although additional biomarkers are required for accurate classification of luminal A, luminal B, and HER2-enriched cancers. IMPACT: Epidemiologic studies relying on three-biomarker IHC status for subtype classification should use caution when distinguishing luminal A from luminal B and when interpreting findings for HER2-enriched cancers.

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Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

March 2016

Volume

25

Issue

3

Start / End Page

470 / 478

Location

United States

Related Subject Headings

  • Tissue Array Analysis
  • Immunohistochemistry
  • Humans
  • Female
  • Epidemiology
  • Breast Neoplasms
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 11 Medical and Health Sciences
 

Citation

APA
Chicago
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MLA
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Allott, E. H., Cohen, S. M., Geradts, J., Sun, X., Khoury, T., Bshara, W., … Troester, M. A. (2016). Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium. Cancer Epidemiol Biomarkers Prev, 25(3), 470–478. https://doi.org/10.1158/1055-9965.EPI-15-0874
Allott, Emma H., Stephanie M. Cohen, Joseph Geradts, Xuezheng Sun, Thaer Khoury, Wiam Bshara, Gary R. Zirpoli, et al. “Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium.Cancer Epidemiol Biomarkers Prev 25, no. 3 (March 2016): 470–78. https://doi.org/10.1158/1055-9965.EPI-15-0874.
Allott EH, Cohen SM, Geradts J, Sun X, Khoury T, Bshara W, et al. Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium. Cancer Epidemiol Biomarkers Prev. 2016 Mar;25(3):470–8.
Allott, Emma H., et al. “Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium.Cancer Epidemiol Biomarkers Prev, vol. 25, no. 3, Mar. 2016, pp. 470–78. Pubmed, doi:10.1158/1055-9965.EPI-15-0874.
Allott EH, Cohen SM, Geradts J, Sun X, Khoury T, Bshara W, Zirpoli GR, Miller CR, Hwang H, Thorne LB, O’Connor S, Tse C-K, Bell MB, Hu Z, Li Y, Kirk EL, Bethea TN, Perou CM, Palmer JR, Ambrosone CB, Olshan AF, Troester MA. Performance of Three-Biomarker Immunohistochemistry for Intrinsic Breast Cancer Subtyping in the AMBER Consortium. Cancer Epidemiol Biomarkers Prev. 2016 Mar;25(3):470–478.

Published In

Cancer Epidemiol Biomarkers Prev

DOI

EISSN

1538-7755

Publication Date

March 2016

Volume

25

Issue

3

Start / End Page

470 / 478

Location

United States

Related Subject Headings

  • Tissue Array Analysis
  • Immunohistochemistry
  • Humans
  • Female
  • Epidemiology
  • Breast Neoplasms
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 11 Medical and Health Sciences