Research Papers:
Longitudinal serum metabolomics evaluation of trastuzumab and everolimus combination as pre-operative treatment for HER-2 positive breast cancer patients
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Abstract
Elodie Jobard1,2, Olivier Trédan2, Thomas Bachelot2, Arnaud M. Vigneron3, Céline Mahier Aït-Oukhatar4, Monica Arnedos5, Maria Rios6, Jacques Bonneterre7, Véronique Diéras8, Marta Jimenez4, Jean-Louis Merlin9,10, Mario Campone11 and Bénédicte Elena-Herrmann1
1Université de Lyon, Institut des Sciences Analytiques, UMR 5280, CNRS, Université Lyon 1, ENS de Lyon, Villeurbanne, France
2Université de Lyon, Centre Léon Bérard, Département d’oncologie médicale, Lyon, France
3Université de Lyon, Centre de Cancérologie de Lyon, UMR Inserm 1052 CNRS 5286, Centre Léon Bérard, Lyon, France
4R&D Unicancer, UNICANCER, Paris, France
5Department of Medicine, Gustave Roussy, Villejuif, France
6Department of Medical Oncology, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France
7Department of Medical Oncology, Centre Oscar Lambret, Lille, France
8Department of Medical Oncology, Institut Curie, Paris, France
9CNRS UMR7039 CRAN, Université de Lorraine, Vandoeuvre-les-Nancy, France
10Department of Biopathology Unit, Institut de Cancérologie de Lorraine, Vandoeuvre-Les-Nancy, France
11Institut de Cancérologie de l’Ouest, Centre René Gauducheau, Saint-Herblain, France
Correspondence to:
Bénédicte Elena-Herrmann, email: [email protected]
Olivier Trédan, email: [email protected]
Keywords: HER-2 positive breast cancer, metabolomics, nuclear magnetic resonance, targeted therapies, mTOR inhibitor
Received: April 04, 2017 Accepted: May 23, 2017 Published: June 28, 2017
ABSTRACT
The mammalian target of rapamycin complex 1 (mTORC1) is an attractive target for HER-2 positive breast cancer therapy because of its key role in protein translation regulation, cell growth and metabolism. We present here a metabolomic investigation exploring the impact of mTOR inhibition on serum metabolic profiles from patients with non-metastatic breast cancer overexpressing HER-2.
Baseline, treatment-related and post-treatment serum samples were analyzed for 79 patients participating in the French clinical trial RADHER, in which randomized patients with HER-2 positive breast cancer received either trastuzumab alone (arm T) or a trastuzumab and everolimus combination (arm T+E). Longitudinal series of NMR serum metabolic profiles were exploited to investigate treatment effects on the patients metabolism over time, in both group.
Trastuzumab and everolimus combination induces faster changes in patients metabolism than trastuzumab alone, visible after only one week of treatment as well as a residual effect detectable up to three weeks after ending the treatment. These metabolic fingerprints highlight the involvement of several metabolic pathways reflecting a systemic effect, particularly on the liver and visceral fat. Comparison of serum metabolic profiles between the two arms shows that everolimus, an mTORC1 inhibitor, is responsible for host metabolism modifications observed in arm T+E.
In HER-2 positive breast cancer, our metabolomic approach confirms a fast and persistent host metabolism modification caused by mTOR inhibition.
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PII: 18784