Redefining the HER2 Oncobiomarker: A Relevant Case Report

In multiple studies anti HER2 therapy combined with chemotherapy demonstrated a marked improvement in disease free survival as adjuvant therapy and as treatment for metastatic breast cancer compared to chemotherapy alone for patients with tumors defined as being HER2 positive [1]. Because of these remarkable results, an expert ASCO/CAP panel in 2013 expanded the definitions of HER2 positive tumors with the hope of allowing more patients to receive and potentially benefit from receiving anti HER2 therapy [2]. In this report, a patient whose tumor would have been defined as HER2 negative until 2007 but after 2013 has been defined as HER2 positive is presented. Per current National Comprehensive Cancer Network Guidelines (NCCN) guidelines, anti HER2 therapy combined with chemotherapy is considered the preferred treatment for her metastatic disease [1]. However, after 2013 CDK4/6 inhibitors in combination with aromatase inhibitor therapy have been shown to be very effective therapy for metastatic breast cancer and would be considered a preferred choice had the HER2 status of her tumor been based on the 2007 guidelines [3]. Yet, CDK4/6 inhibitors are only approved for patients with HER2 negative breast cancers. This report underscores the dilemma that occurs when the definition of a molecular marker as a predictor of benefit is expanded to include additional tumors that previously would have been labeled “negative” but would now be considered “positive”. Whenever possible, the expansion (or contraction) of the definition of a positive molecular marker of efficacy should be based on clinical reports of the efficacy of the targeted agents in patients with such tumors.