Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy

Olga Martínez-Sáez, Tomás Pascual, Fara Brasó-Maristany, Nuria Chic, Blanca González-Farré, Esther Sanfeliu, Adela Rodríguez, Débora Martínez, Patricia Galván, Anna Belén Rodríguez, Francesco Schettini, Benedetta Conte, Maria Vidal, Barbara Adamo, Antoni Martínez, Montserrat Muñoz, Reinaldo Moreno, Patricia Villagrasa, Fernando Salvador, Eva M. CiruelosIris Faull, Justin I. Odegaard, Aleix Prat

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number8
Journalnpj Breast Cancer
Issue number1
Publication statusPublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

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