An update of the ESMO recommendations for the use of NGS in advanced cancer has been published very recently [93]. The authors consider that, since NGS can substitute germline BRCA testing in most patients and ESR1 mutations have been reclassified as level 1A, performing NGS in advanced breast cancer (tumor or plasma) is recommended in patients with HR-positive/HER2-negative disease after resistance to endocrine therapy. The gene discussed is ESR1; the disease is neoplasm.