To treat or not to treat: HER2 equivocal is the matter!

With the introduction of the 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for human epidermal growth factor receptor type 2 (HER2) testing, some authors noticed an increase in equivocal HER2 determinations. Indeed, many retrospective assessments showed an increase of up to 14% in the number of equivocal cases by immunohistochemistry and fluorescence in situ hybridization. In these cases, if after reflex testing with the same and/or an alternative specimen the HER2 test result is deemed to be equivocal, the ASCO/CAP guidelines recommend to consider HER2-targeted therapy. However, due to the absence of prospective data on the efficacy of anti-HER2 therapy in equivocal HER2 breast cancer (BC), the therapeutic decision is extremely complex, especially in the adjuvant and neoadjuvant settings. In this perspective paper, we analyse the available retrospective data aiming to answer to the dilemma whether to treat or not to treat HER2 equivocal cases with a HER2-targeted therapy.