Equivocal is Not a Genomic Subtype

Per NCCN guidelines, all newly diagnosed, recurrent, and metastatic breast cancers are evaluated for HER2 positivity. Tumors highly amplified for HER2 receptor protein expression are predicted to respond to anti-HER2 therapies. Thus, accurate reporting of the HER2 genomic subtype of each and every breast cancer is of critical importance for treatment planning and the patient’s clinical outcome.

So why are 20% of breast cancers reported by pathologists as “Equivocal” instead of giving the clinician an actionable HER2 genomic subtype? Here is the definition of “equivocal” from the Merriam Webster Online dictionary:


In the age of precision medicine, can’t we do better than this? The answer is YES! We know that approximately 25% of breast cancers are unequivocally HER2-Positive and predicted to respond to anti-HER2 therapies. Recent data shows that a subset of patients with low expression of the HER2 receptor protein may also respond to anti-HER2 therapies. The response of these HER2-Low patients to the drug Herceptin is being studied in a large (> 3000 patients) clinical trial called NSABP-B47. How to treat these patients will be clearer after the study results are announced, but the majority of patients currently being classified as “Equivocal” actually fall into the HER2-Low category. And then there are the HER2-Negative tumors with no expression of the HER2 receptor protein and thus no target for the drug to bind to on their tumor cells. Patients with HER2-Negative tumors will be treated with other drugs so it is essential to definitively define this group.

It is time to remove the word “Equivocal” from all breast cancer reports and replace it with the actual HER2 genomic subtype of the patient’s tumor (HER2-Positive, HER2-Low, HER2 Negative.) Clinical laboratories have the technology to make this happen for breast cancer patients so what are we waiting for??

Shelly Gunn MD, PhD | Pathologist | September 25, 2016

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