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Breast Cancer Res Treat. 2018 Nov;172(2):327-338. doi: 10.1007/s10549-018-4889-5. Epub 2018 Aug 17.

Comparison of central laboratory assessments of ER, PR, HER2, and Ki67 by IHC/FISH and the corresponding mRNAs (ESR1, PGR, ERBB2, and MKi67) by RT-qPCR on an automated, broadly deployed diagnostic platform.

Author information

1
Division of Oncology Research and Development, Cepheid, Sunnyvale, CA, USA.
2
Department of Pathology, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, STE. 5409, Los Angeles, CA, 90033-0800, USA.
3
Oregon Health and Science University/Knight Cancer Institute, Portland, OR, USA.
4
Medical University of Gdansk, Gdansk, Poland.
5
Military Institute of Medicine, Warsaw, Poland.
6
Oncology Center, Opole, Poland.
7
Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki, Japan.
8
Geneuity/MPLN, Maryville, TN, USA.
9
Department of Human Life Science, School of Nursing, Josai University, Sakado, Japan.
10
Indivumed, Hamburg, Germany.
11
Medical and Scientific Affairs and Strategy, Oncology, Cepheid, Sunnyvale, CA, USA.
12
Department of Pathology, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, STE. 5409, Los Angeles, CA, 90033-0800, USA. Michael.Press@med.usc.edu.

Abstract

PURPOSE:

The methods (IHC/FISH) typically used to assess ER, PR, HER2, and Ki67 in FFPE specimens from breast cancer patients are difficult to set up, perform, and standardize for use in low and middle-income countries. Use of an automated diagnostic platform (GeneXpert®) and assay (Xpert® Breast Cancer STRAT4) that employs RT-qPCR to quantitate ESR1, PGR, ERBB2, and MKi67 mRNAs from formalin-fixed, paraffin-embedded (FFPE) tissues facilitates analyses in less than 3 h. This study compares breast cancer biomarker analyses using an RT-qPCR-based platform with analyses using standard IHC and FISH for assessment of the same biomarkers.

METHODS:

FFPE tissue sections from 523 patients were sent to a College of American Pathologists-certified central reference laboratory to evaluate concordance between IHC/FISH and STRAT4 using the laboratory's standard of care methods. A subset of 155 FFPE specimens was tested for concordance with STRAT4 using different IHC antibodies and scoring methods.

RESULTS:

Concordance between STRAT4 and IHC was 97.8% for ESR1, 90.4% for PGR, 93.3% for ERBB2 (IHC/FISH for HER2), and 78.6% for MKi67. Receiver operating characteristic curve (ROC) area under the curve (AUC) values of 0.99, 0.95, 0.99, and 0.85 were generated for ESR1, PGR, ERBB2, and MKi67, respectively. Minor variabilities were observed depending on the IHC antibody comparator used.

CONCLUSION:

Evaluation of breast cancer biomarker status by STRAT4 was highly concordant with central IHC/FISH in this blinded, retrospectively analyzed collection of samples. STRAT4 may provide a means to cost-effectively generate standardized diagnostic results for breast cancer patients in low- and middle-income countries.

KEYWORDS:

Breast cancer biomarker assays; Estrogen receptor; FISH; Human epidermal growth factor receptor 2; IHC; Progesterone receptor; STRAT4; Tumor proliferation rate

PMID:
30120700
PMCID:
PMC6208911
DOI:
10.1007/s10549-018-4889-5
[Indexed for MEDLINE]
Free PMC Article

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