TY - JOUR
T1 - Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy
AU - Martínez-Sáez, Olga
AU - Pascual, Tomás
AU - Brasó-Maristany, Fara
AU - Chic, Nuria
AU - González-Farré, Blanca
AU - Sanfeliu, Esther
AU - Rodríguez, Adela
AU - Martínez, Débora
AU - Galván, Patricia
AU - Rodríguez, Anna Belén
AU - Schettini, Francesco
AU - Conte, Benedetta
AU - Vidal, Maria
AU - Adamo, Barbara
AU - Martínez, Antoni
AU - Muñoz, Montserrat
AU - Moreno, Reinaldo
AU - Villagrasa, Patricia
AU - Salvador, Fernando
AU - Ciruelos, Eva M.
AU - Faull, Iris
AU - Odegaard, Justin I.
AU - Prat, Aleix
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85100393653&partnerID=8YFLogxK
U2 - 10.1038/s41523-021-00218-8
DO - 10.1038/s41523-021-00218-8
M3 - Article
SN - 2374-4677
VL - 7
JO - npj Breast Cancer
JF - npj Breast Cancer
IS - 1
M1 - 8
ER -
