A recent study of PTEN expression and PIK3CA mutation in HER2+ patients with either recurrent disease after trastuzumab treatment or progression of metastatic disease while on trastuzumab therapy showed a significantly increased frequency of either PTEN loss or PIK3CA mutation compared to untreated HER2+ tumors, but PIK3CA mutation status alone did not appear to be significantly enriched in the clinically trastuzumab-refractory cohort [19]. This evidence concerns the gene ERBB2 and metastatic neoplasm.