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High Fidelity of Breast Biomarker Metrics

A 10-Year Experience in a Single, Large Academic Institution

Zhang, Huina, MD, PhD; Han, Min, MD, PhD; Varma, Kavita R., MD; Clark, Beth Z., MD; Bhargava, Rohit, MD; Dabbs, David J., MD

Applied Immunohistochemistry & Molecular Morphology: November/December 2018 - Volume 26 - Issue 10 - p 697–700
doi: 10.1097/PAI.0000000000000697
Research Articles

Purpose: Recommendations for standardization of breast biomarkers including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) led to the creation of American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines to provide continuous guidance. Included in these recommendations is the “ongoing assay assessment procedures.” We report these biomarker metrics as there is a dearth of published information on this topic.

Materials and Methods: ER, PR, and HER2 positivity rates of all newly diagnosed, recurrent, and metastatic invasive breast cancers on core biopsies, and repeated testing on resection specimen by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) were collected from April 1, 2008 to December 31, 2017.

Results: The positivity rates of ER, PR, and HER2 over almost 10 years of monitoring showed high fidelity. Total ER-positive rate was 83.6% (81.4% to 86.8%), ER+/PR+ was 71.7% (68.6% to 75.5%), ER+/PR− was 17.6% (11.0% to 15.0%), ER−/PR− was 16.0% (13.5% to 18.2%), and ER−/PR+ was 0.6% (0.2% to 1.0%). The HER2-positive rate was 13.7% (10.2% to 17.4%) including 9.9% (7.3% to 11.9%) by IHC and 3.8% (1.9% to 5.9%) by FISH reflexed from IHC 2+ results. FISH amplification rate of HER2 IHC 2+ cases was 11.0% (5.8% to 19.2%). Annual quality-assurance check for HER2 IHC/FISH percent positive and percent negative agreement (as defined by Food and Drug Administration) was 96% to 100%.

Conclusions: This longitudinal active assessment of 9564 breast biomarker cases shows the achievement of high fidelity of breast biomarker results when following the ASCO/CAP guidelines. Continuous monitoring of breast biomarkers may minimize assay analytical drift and assure quality clinically relevant results.

Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA

The authors declare no conflict of interest.

Reprints: David J. Dabbs, MD, Department of Pathology, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (e-mail:

Received June 21, 2018

Accepted July 8, 2018

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