Circulating tumor DNA dynamics using a standardized multi-gene panel in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy

Brief communication Circulating tumor DNA (ctDNA) levels may predict response to anticancer drugs 1 , including CDK4/6 inhibitors and endocrine therapy combinations (CDK4/6i+ET) 2 ; however, critical questions remain unanswered such as which assay or statistical method to use 3 . Here, we obtained paired plasma samples at baseline and week 4 in 45 consecutive patients with advanced breast cancer treated with CDK4/6i+ET. ctDNA was detected in 96% of cases using the 74-gene Guardant360 assay 4,5 . A variant allele fraction ratio (VAFR) was calculated for each of the 79 detected mutations between both time-points. Mean of all VAFRs (mVAFR) was computed for each patient. In our dataset, mVAFR was significantly associated with progression-free survival (PFS). Baseline VAF, on-treatment VAF or absolute changes in VAF were not associated with PFS. These findings demonstrate that ctDNA dynamics using a standardized multi-gene panel and a unique methodological approach predicts treatment outcome. Clinical trials in patients with an unfavorable ctDNA response are needed.