The results of the research carried out in this work confirm previous findings that ESR1 mutations are more frequent in metastatic luminal breast cancer patients irrespective of the type of therapy (endocrine or chemotherapy-based treatments) [38,42] and reveal that pathogenic ESR1 mutations appear mainly during progression, most likely as a result of the selective pressure of endocrine treatments, as no mutations were found in primary tumor samples. Here, ESR1 is linked to breast cancer.