Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer

Abstract Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two cancer-derived blood biomarkers that inform on patient prognosis and treatment efficacy in breast cancer. We prospectively evaluated the clinical validity of quantifying both CTCs (CellSearch) and ctDNA (targeted next-...

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Autores principales:	Amanda Bortolini Silveira, François-Clément Bidard, Marie-Laure Tanguy, Elodie Girard, Olivier Trédan, Coraline Dubot, William Jacot, Anthony Goncalves, Marc Debled, Christelle Levy, Jean-Marc Ferrero, Christelle Jouannaud, Maria Rios, Marie-Ange Mouret-Reynier, Florence Dalenc, Caroline Hego, Aurore Rampanou, Benoit Albaud, Sylvain Baulande, Frédérique Berger, Jérôme Lemonnier, Shufang Renault, Isabelle Desmoulins, Charlotte Proudhon, Jean-Yves Pierga
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/defc150529374d2a9813a467847b33d8
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spelling	oai:doaj.org-article:defc150529374d2a9813a467847b33d82021-12-02T19:12:35ZMultimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer10.1038/s41523-021-00319-42374-4677https://doaj.org/article/defc150529374d2a9813a467847b33d82021-09-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00319-4https://doaj.org/toc/2374-4677Abstract Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two cancer-derived blood biomarkers that inform on patient prognosis and treatment efficacy in breast cancer. We prospectively evaluated the clinical validity of quantifying both CTCs (CellSearch) and ctDNA (targeted next-generation sequencing). Their combined value as prognostic and early monitoring markers was assessed in 198 HER2-negative metastatic breast cancer patients. All patients were included in the prospective multicenter UCBG study COMET (NCT01745757) and treated by first-line chemotherapy with weekly paclitaxel and bevacizumab. Blood samples were obtained at baseline and before the second cycle of chemotherapy. At baseline, CTCs and ctDNA were respectively detected in 72 and 74% of patients and were moderately correlated (Kendall’s τ = 0.3). Only 26 (13%) patients had neither detectable ctDNA nor CTCs. Variants were most frequently observed in TP53 and PIK3CA genes. KMT2C/MLL3 variants detected in ctDNA were significantly associated with a lower CTC count, while the opposite trend was seen with GATA3 alterations. Both CTC and ctDNA levels at baseline and after four weeks of treatment were correlated with survival. For progression-free and overall survival, the best multivariate prognostic model included tumor subtype (triple negative vs other), grade (grade 3 vs other), ctDNA variant allele frequency (VAF) at baseline (per 10% increase), and CTC count at four weeks (≥5CTC/7.5 mL). Overall, this study demonstrates that CTCs and ctDNA have nonoverlapping detection profiles and complementary prognostic values in metastatic breast cancer patients. A comprehensive liquid-biopsy approach may involve simultaneous detection of ctDNA and CTCs.Amanda Bortolini SilveiraFrançois-Clément BidardMarie-Laure TanguyElodie GirardOlivier TrédanCoraline DubotWilliam JacotAnthony GoncalvesMarc DebledChristelle LevyJean-Marc FerreroChristelle JouannaudMaria RiosMarie-Ange Mouret-ReynierFlorence DalencCaroline HegoAurore RampanouBenoit AlbaudSylvain BaulandeFrédérique BergerJérôme LemonnierShufang RenaultIsabelle DesmoulinsCharlotte ProudhonJean-Yves PiergaNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-9 (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 Amanda Bortolini Silveira François-Clément Bidard Marie-Laure Tanguy Elodie Girard Olivier Trédan Coraline Dubot William Jacot Anthony Goncalves Marc Debled Christelle Levy Jean-Marc Ferrero Christelle Jouannaud Maria Rios Marie-Ange Mouret-Reynier Florence Dalenc Caroline Hego Aurore Rampanou Benoit Albaud Sylvain Baulande Frédérique Berger Jérôme Lemonnier Shufang Renault Isabelle Desmoulins Charlotte Proudhon Jean-Yves Pierga Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer
description	Abstract Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two cancer-derived blood biomarkers that inform on patient prognosis and treatment efficacy in breast cancer. We prospectively evaluated the clinical validity of quantifying both CTCs (CellSearch) and ctDNA (targeted next-generation sequencing). Their combined value as prognostic and early monitoring markers was assessed in 198 HER2-negative metastatic breast cancer patients. All patients were included in the prospective multicenter UCBG study COMET (NCT01745757) and treated by first-line chemotherapy with weekly paclitaxel and bevacizumab. Blood samples were obtained at baseline and before the second cycle of chemotherapy. At baseline, CTCs and ctDNA were respectively detected in 72 and 74% of patients and were moderately correlated (Kendall’s τ = 0.3). Only 26 (13%) patients had neither detectable ctDNA nor CTCs. Variants were most frequently observed in TP53 and PIK3CA genes. KMT2C/MLL3 variants detected in ctDNA were significantly associated with a lower CTC count, while the opposite trend was seen with GATA3 alterations. Both CTC and ctDNA levels at baseline and after four weeks of treatment were correlated with survival. For progression-free and overall survival, the best multivariate prognostic model included tumor subtype (triple negative vs other), grade (grade 3 vs other), ctDNA variant allele frequency (VAF) at baseline (per 10% increase), and CTC count at four weeks (≥5CTC/7.5 mL). Overall, this study demonstrates that CTCs and ctDNA have nonoverlapping detection profiles and complementary prognostic values in metastatic breast cancer patients. A comprehensive liquid-biopsy approach may involve simultaneous detection of ctDNA and CTCs.
format	article
author	Amanda Bortolini Silveira François-Clément Bidard Marie-Laure Tanguy Elodie Girard Olivier Trédan Coraline Dubot William Jacot Anthony Goncalves Marc Debled Christelle Levy Jean-Marc Ferrero Christelle Jouannaud Maria Rios Marie-Ange Mouret-Reynier Florence Dalenc Caroline Hego Aurore Rampanou Benoit Albaud Sylvain Baulande Frédérique Berger Jérôme Lemonnier Shufang Renault Isabelle Desmoulins Charlotte Proudhon Jean-Yves Pierga
author_facet	Amanda Bortolini Silveira François-Clément Bidard Marie-Laure Tanguy Elodie Girard Olivier Trédan Coraline Dubot William Jacot Anthony Goncalves Marc Debled Christelle Levy Jean-Marc Ferrero Christelle Jouannaud Maria Rios Marie-Ange Mouret-Reynier Florence Dalenc Caroline Hego Aurore Rampanou Benoit Albaud Sylvain Baulande Frédérique Berger Jérôme Lemonnier Shufang Renault Isabelle Desmoulins Charlotte Proudhon Jean-Yves Pierga
author_sort	Amanda Bortolini Silveira
title	Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer
title_short	Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer
title_full	Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer
title_fullStr	Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer
title_full_unstemmed	Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer
title_sort	multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/defc150529374d2a9813a467847b33d8
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Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer

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