A clinical report compared the circulating tumor DNA (ctDNA) pre-exposure and after-exposure to CDK4/6 inhibitor (Palbociclib or Ribociclib) in three metastatic BC patients, discovering the substitution in donor splicing site of exon 8 of the RB1 gene, substitution in donor splicing site of exon 22 together with exon 19 deletion and exon 3 insertion, mutation in exon 16 H483Y, respectively 46. Here, RB1 is linked to breast cancer.