In the largest clinical series published so far, several alterations in oncogenes or tumor suppressor genes (TSGs) occurring more commonly in metastatic HR+ HER2-BC (mBC) than in early BC (eBC) specimens were reported [2–4]: the most frequent oncogenic mutations involved ESR1, ERBB2 and FGFR4 genes, while TP53, RB1, ATR, FAT1 and ARID1 were the most commonly altered TSGs. Here, ESR1 is linked to breast cancer.