Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy
Abstract 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...
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2021-02-01
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Online Access: | https://doi.org/10.1038/s41523-021-00218-8 |
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doaj-9539a7ac44b6431f941c92563bf19fa92021-02-07T12:03:46ZengNature Publishing Groupnpj Breast Cancer2374-46772021-02-01711610.1038/s41523-021-00218-8Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapyOlga Martínez-Sáez0Tomás Pascual1Fara Brasó-Maristany2Nuria Chic3Blanca González-Farré4Esther Sanfeliu5Adela Rodríguez6Débora Martínez7Patricia Galván8Anna Belén Rodríguez9Francesco Schettini10Benedetta Conte11Maria Vidal12Barbara Adamo13Antoni Martínez14Montserrat Muñoz15Reinaldo Moreno16Patricia Villagrasa17Fernando Salvador18Eva M. Ciruelos19Iris Faull20Justin I. Odegaard21Aleix Prat22SOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupDepartment of Medical Oncology, Hospital Clinic of BarcelonaSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupDepartment of Pathology, Hospital Clinic of BarcelonaSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupSOLTI Cancer Research GroupGuardant Health, Inc.Guardant Health, Inc.SOLTI Cancer Research GroupAbstract 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.https://doi.org/10.1038/s41523-021-00218-8 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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. Ciruelos Iris Faull Justin I. Odegaard Aleix Prat |
spellingShingle |
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. Ciruelos Iris Faull Justin I. Odegaard Aleix Prat Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy npj Breast Cancer |
author_facet |
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. Ciruelos Iris Faull Justin I. Odegaard Aleix Prat |
author_sort |
Olga Martínez-Sáez |
title |
Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy |
title_short |
Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy |
title_full |
Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy |
title_fullStr |
Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy |
title_full_unstemmed |
Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy |
title_sort |
circulating tumor dna dynamics in advanced breast cancer treated with cdk4/6 inhibition and endocrine therapy |
publisher |
Nature Publishing Group |
series |
npj Breast Cancer |
issn |
2374-4677 |
publishDate |
2021-02-01 |
description |
Abstract 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. |
url |
https://doi.org/10.1038/s41523-021-00218-8 |
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