For patients with HER2-negative metastatic disease, the treatment approach should be tailored according to a number of prognostic factors, which include endocrine tumor status, other possible actionable targets (androgen receptor, BRCA mutation), hormonal status, prior therapies (adjuvant and metastatic), disease-free interval, comorbidities, performance status, burden of metastatic disease, patient preferences, prior toxicities, geographic accessibility to the closest cancer treatment center, and available as well as affordable cancer therapies. The gene discussed is ERBB2; the disease is cancer.