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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9539a7ac44b6431f941c92563bf19fa9
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spelling	oai:doaj.org-article:9539a7ac44b6431f941c92563bf19fa92021-12-02T14:11:11ZCirculating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy10.1038/s41523-021-00218-82374-4677https://doaj.org/article/9539a7ac44b6431f941c92563bf19fa92021-02-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00218-8https://doaj.org/toc/2374-4677Abstract 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.Olga Martínez-SáezTomás PascualFara Brasó-MaristanyNuria ChicBlanca González-FarréEsther SanfeliuAdela RodríguezDébora MartínezPatricia GalvánAnna Belén RodríguezFrancesco SchettiniBenedetta ConteMaria VidalBarbara AdamoAntoni MartínezMontserrat MuñozReinaldo MorenoPatricia VillagrasaFernando SalvadorEva M. CiruelosIris FaullJustin I. OdegaardAleix PratNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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
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.
format	article
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
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 Portfolio
publishDate	2021
url	https://doaj.org/article/9539a7ac44b6431f941c92563bf19fa9
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Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy

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