Aug 3, 2016

Fish-Equivocal HER2 (ERBB2) Amplification in Breast Cancer


FISH-EQUIVOCAL HER2 (ERBB2) amplification


ERBB2 (a.k.a. HER2) testing must be requested on every primary invasive breast cancer. Additionally, it is recommended to perform ERBB2 testing on metastatic sites, classified as stage IV, if tissue sample is available. This is to guide decision to pursue ERBB2-targeted therapy.

This Interpretation Guide is based on ASCO (American Society of Clinical Oncology) and CAP (College of American Pathologists) recommendations for ERBB2 testing in breast cancer (Wolff AC, et al. 2013)*.

It does not claim to be complete in reference to clinical usage and appraisal of results. Moreover, it should be regarded as a practical help of ERBB2 FISH evaluation in regards to clinical decision making.


• A prognostic indicator for patients with both node-positive or node-negative primary and metastatic breast cancer

• Guiding therapy, as patients with HER2 amplification may be candidates for therapies that target the human Epidermal Growth Factor Receptor 2 (HER2) protein (e.g., trastuzumab [Herceptin], pertuzumab, lapatinib)

• Confirming the presence of HER2 amplification in cases with 2+ (low level) or 3+ (high level) HER2 overexpression by immunohistochemistry





1) Using ERBB2/CEN 17 ratio alone can be misleading in cases of gains or losses of the centromeric region of chromosome 17. Cases with ERBB2 copy number < 4.0 should be reported
as ERBB2-positive if ratio is  2.0.
2) Monosomy with low-level amplification of ERBB2.


Code: XX051
Department: FISH
Name: FISH-EQUIVOCAL HER2 (ERBB2) amplification
Specimen: Formalin fixed paraffin embedded tissue block / three 4μ sections on Poly-L-Lysine coated slides. Ship at room temperature. Clinical history is mandatory.
Room temperature: NA
Refrigerated: NA
Frozen: NA
Method: FISH
Report: Sample Daily by 4 pm; Report in 5 days.
Usage: This assay is recommended ( ASCO / CAP guidelines 2013) in all cases where initial HER2 test result is equivocal. Reflex testing should be performed on the same specimen using an alternative probe like HER2 / D17S122. This probe targets an area which is different from the usual centromere probe for HER2. It is important to further identify equivocal results as it affects treatment protocols.


1. Wolff AC, Hammond ME, Hicks DG, et al: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society for Clinical Oncology/College of American
Pathologists clinical practice guideline update. J Clin Onc 2013 Nov 1;31(31):3997-4013

2. Perez EA, Roche PC, Jenkins RB, et al: HER2 testing in patients with breast cancer: poor correlation between weak positively by immunohistochemistry and gene amplification by fluorescence in situ hybridization. Mayo Clin Proc 2002 Feb;77(2):148-154

3. Romond EH, Perez EA, Bryant J, et al: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005 Oct 20;353(16):1673-1684

4. Perez EA, Romond EH, Suman VJ, et al: Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer:
joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol 2011 Sep 1;29(25):3366-3373

5. Blumenthal GM, Scher NS, Cortazar P, et al: First FDA approval of dual anti-HER2 regimen: pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer. Clin Cancer Res 2013 Sep 5;19(18):4911-4916

6. Robidoux A, Tang G, Rastogi P: Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol 2013 epub: 2013 Oct 3

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