Would you give a HER2 targeted agent to a patient whose initial cancer was ER/PR positive, HER2 negative but now with metastatic disease that is ER positive, PR negative, HER2 2+, FISH equivocal?

Discordance of HER from primary to metastatic status is seen in about 5-10% of cases (1). Little data are available regarding outcomes of these cases, but responses have been seen in patients with HER2-negative primary tumors and HER2+ metastases (2), and I have certainly observed this personally. In this case, I would use the revised ASCO/CAP guidelines to classify this patient's HER2 status (3). If positive, I would determine if there were other metastatic lesions amenable to biopsy since clonal divergence can be seen in metastatic lesions with respect to hormone and HER2 receptor status and to genotypic status with DNA sequencing - if one of the lesions were HER2-positive using ASCO/CAP criteria, especially in an organ, I would use first...