Drago and coworkers have explored the mechanisms of resistance to endocrine and targeted therapies in a cohort of ER+/HER2- breast cancer patients and have shown that patients with FGFR1-amplified tumors: (i) have a tendency to a more frequent PR- disease (47% vs 20%) and coexisting TP53 mutations (41% vs 21%); and, (ii) display a shorter time to progression disease following endocrine therapy alone or in combination with a mTOR inhibitor [187]. The gene discussed is TP53; the disease is breast cancer.