In the multivariate analysis, we identified fourteen independent prognostic variables for survival in metastatic HER2-positive breast cancer: age, Charlson–Deyo score, histology, HER2 IHC expression, ER expression, PR expression, the number of metastatic sites, the location of metastases, first-line chemotherapy, anti-HER2 therapy, hormone-blocking therapy, surgery of the primary site (breast), surgery of the non-primary site, and palliative treatment (to alleviate symptoms). The gene discussed is ESR1; the disease is breast cancer.