HER2 Assessment in Breast Cancer

Sara M. Tolaney, MD, MPH: Generally, when we test for HER2 [human epidermal growth factor receptor 2], initially at Dana-Farber Cancer Institution in Boston, Massachusetts, we do immunohistochemistry [IHC] staining. We will stain for HER2 by IHC. If it comes back as IHC 3+, we do consider the tumor HER2 positive. Whereas if a tumor comes back as 1+ staining, we would consider the tumor HER2 negative. And if it comes back at 2+, or that intermediate staining level, then it’s considered HER2 equivocal, meaning that we then need to go to a second test to assess for positivity. At that point, we go on to do a FISH [fluorescence in situ hybridization] test.

The FISH test really looks at the ratio of HER2 to CEP17. If that ratio is greater than 2 and the HER2 copy number is greater than or equal to 4, we consider the tumor to be HER2 positive.

If the HER2 ratio is less than 2 but the HER2 copy number is greater than 6, we can still consider that HER2 positive. In that case, we just need to go back and retest the copy number to see if it is consistently greater than 6. And if it’s between 4 and 6, you also need to consider retesting and recounting to see if it could be greater than 6. That could still be considered HER2 positive, even though the ratio is less than 2. Again, there are these subtle cases where it gets a little tricky, particularly when the copy number is in that 4-to-6 range or if the ratio is less than 2. The easiest cases are when it’s HER2 3+ and the ratio is greater than 2 and the copy number is greater than 4.

Transcript edited for clarity.