Meric–Bernstam and coworkers explored, by high-depth next generation sequencing, 257 patients with metastatic breast cancer, including 165 patients with HR+/HER2- breast cancer; in this last group of patients, PIK3CA (32%) and TP53 (29%) were the most frequently mutated genes and TP53 mutations were associated with shorter overall survival and progression-free survival [326]. Here, HR is linked to breast cancer.