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MEDICINE

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of the ASCO-College of American Pathologists guidelines with
FISH scores used for enrollment in Breast Cancer International
Research Group clinical trials. J Clin Oncol. 2016;34(29):3518-
3528. doi: 10.1200/JCO.2016.66.6693.

16. Fehrenbacher L, Jeong J-H, Rastogi P, et al. NSABP B-47: a ran-
domized phase III trial of adjuvant therapy comparing chemo-
therapy alone to chemotherapy plus trastuzumab in women with
node-positive or high-risk node-negative HER2-low invasive
breast cancer. Poster presented at: 2013 ASCO Annual Meeting.
J Clin Oncol. 2013;31(suppl; abstr TPS1139).

Abstract
In the era of precision medicine, human epidermal growth factor
receptor 2 (HER2) is the most important predictive and prognostic
biomarker in breast cancer. The HER2 status of a patient’s tumor
can be analyzed at the protein level by immunohistochemistry (IHC)
and at the chromosome level by in situ hybridization (ISH) tech-
niques to determine the average HER2 gene copy number. Yet, de-
spite these two complementary methods for HER2 testing, there
remains a subset of high-risk breast cancer patients (>20%) whose
HER2 status is reported as “equivocal,” an assessment that provides
no useful information about how to treat the patient.
Given there are 2 FDA approved HER2 assays readily available
in the clinical laboratory, the currently confused state of HER2 test-
ing in breast cancer is perplexing and raises the following questions:
are IHC and dual-probe ISH giving the wrong answer 20% of the
time, or alternatively, could these tests be giving the correct answers
and we are misinterpreting the data? For the past decade, genomic
pathologists have used chromosomal microarrays (CMAs) as a
DNA-based approach for obtaining high-resolution images of
HER2 gene status on chromosome 17. These studies provide con-
firmation that ISH is a reliable method for determining average
HER2 gene copy number, and it is the HER2 ratio denominators
(cep17 or alternative probes) that can introduce instability into the
final results. However, even though CMA provides more detailed
information about chromosome 17 status in breast cancer than con-
ventional cytogenetics or FISH, the complexity of the method and
interpretation make it impractical for routine use by the clinical lab-
oratory as a HER2 testing method. Thus, IHC and fluorescence in
situ hybridization will remain for the foreseeable future, the main-
stay of HER2 testing in breast cancer. The current challenge is thus
not to introduce a new HER2 assay into the clinical laboratory but
rather to develop a strategy for reporting unequivocal, biologically
accurate results using existing FDA-approved testing methods.

22 San Antonio Medicine • March 2018