Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy.
Olga Martínez-SáezTomás PascualFara Brasó-MaristanyNuria ChicBlanca González-FarréEsther SanfeliuAdela RodríguezDébora MartínezPatricia GalvánAnna Belén RodríguezFrancesco SchettiniBenedetta ConteMaría Jesús Vidal LosadaBarbara AdamoAntonio Martinez-PozoMontserrat MuñozReinaldo MorenoPatricia VillagrasaFernando SalvadorEva M CiruelosIris FaullJustin I OdegaardAleix PratPublished in: NPJ breast cancer (2021)
Circulating tumor DNA (ctDNA) levels may predict response to anticancer drugs, including CDK4/6 inhibitors and endocrine therapy combinations (CDK4/6i+ET); however, critical questions remain unanswered such as which assay or statistical method to use. 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. A variant allele fraction ratio (VAFR) was calculated for each of the 79 detected mutations between both timepoints. 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, nor were CA-15.3 levels at baseline, week 4 or the CA-15.3 ratio. 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.
Keyphrases
- circulating tumor
- cell cycle
- cell free
- circulating tumor cells
- free survival
- clinical trial
- high throughput
- copy number
- genome wide
- cell proliferation
- genome wide identification
- case report
- stem cells
- dna methylation
- transcription factor
- magnetic resonance imaging
- young adults
- placebo controlled
- open label
- breast cancer risk
- phase ii