How are HER2 testing results interpreted in breast tumors?

Updated: Mar 20, 2019
  • Author: Oudai Hassan, MD; Chief Editor: Chandandeep Nagi, MD  more...
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Answer

Answer

Interpretation and reporting [13]

In 2018, ASCO/CAP updated their recommendations on how to report HER2 (see Table 5, below). [15]

Table 5. Interpretation and Reporting of HER2 Tests (Open Table in a new window)

Immunohistochemistry (IHC)

Positive

Negative

Equivocal

Only membranous staining is relevant.

Score 3+

Circumferential membrane staining that is complete and >10% of tumor cells

Score 0: No staining observed or

Membrane stating that is incomplete, is faint/barely perceptible, and within ≤10% of tumor cells

 

Score 1+: Incomplete membrane staining that is faint/barely perceptible and within >10% of tumor cells

Score 2+

Weak to moderate complete membrane staining in >10% of tumor cells or

 

Circumferential membrane staining that is intense but within ≤10% of tumor cells

Fluorescence in situ hybridization (FISH) Positive Negative  

At least 20 nonoverlapping cells in two separate areas of invasive carcinoma should be counted.

 

 

 

Tests systems with internal control probe (chromosome enumeration probe [CEP17]): The FISH ratio (ratio of HER2 gene signals to chromosome 17 signals) is reported.

Dual-probe assay

  • HER2/CEP17 ratio ≥2.0; < 4.0 HER2 signals/cell and concurrent IHC 3+
  • HER2/CEP17 ratio < 2.0; ≥6.0 HER2 signals/cell and concurrent IHC 2+ or 3+
  • HER2/CEP17 ratio < 2.0; ≥4.0 and < 6.0 HER2 signals/cell and concurrent IHC 3+
  • HER2/CEP17 ratio ≥2.0; ≥4.0 HER2 signals/cell 

Dual-probe assay

  • HER2/CEP17 ratio < 2.0; < 4.0 HER2 signals/cell
  • HER2/CEP17 ratio ≥2.0; < 4.0 HER2 signals/cell and concurrent IHC 0-1+ or 2+ 
  • HER2/CEP17 ratio < 2.0; ≥6.0 HER2 signals/cell and concurrent IHC 0-1+
  • HER2/CEP17 ratio < 2.0; ≥4.0 and < 6.0 HER2 signals/cell and concurrent IHC 0-1+ or 2+

 

Patients with positive results are considered eligible for trastuzumab therapy

Patients with negative results are not considered eligible for trastuzumab therapy

 

No currently available assay is perfectly accurate in identifying all patients expected to benefit from anti-HER2 therapy. Therefore, a combination of tests may be required on a particular specimen. The pathologist plays an important role in avoiding false-negative and false-positive results.


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