The lower prevalence of likely pathogenic or pathogenic PIK3CA and ESR1 variants in the CTC gDNA fraction may originate from an impaired number of low frequent, highly dynamic, tumor-derived variants (manifested by increased limit of detection; Table S2) compared to the potential germline variants (sequenced in the leukocyte contamination of the CTC-enriched fraction). Here, ESR1 is linked to neoplasm.