title: Pharmacometabolomics study identifies circulating spermidine and tryptophan as potential biomarkers associated with the complete pathological response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer.
abstract: Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. In the present study, we applied a pharmacometabolomics approach to identify biomarkers potentially associated with pathological complete response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer patients. Based on histological response the 34 patients enrolled in the study were subdivided into two groups: good responders (n = 15) and poor responders (n = 19). The pre-treatment serum targeted metabolomics profile of all patients were analyzed by liquid chromatography tandem mass spectrometry and the differences in the metabolomics profile between the two groups was investigated by multivariate partial least squares discrimination analysis. The most relevant metabolites that differentiate the two groups of patients were spermidine and tryptophan. The Good responders showed higher levels of spermidine and lower amounts of tryptophan compared with the poor responders (p < 0.001, q < 0.05). The serum level of these two metabolites identified patients who achieved a pathological complete response with a sensitivity of 90% [0.79-1.00] and a specificity of 0.87% [0.67-1.00]. These preliminary results support the role played by the individual patients' metabolism in determining the response to cancer treatments and may be a useful tool to select patients that are more likely to benefit from the trastuzumab-paclitaxel treatment.
authors.affiliation: Department of Medical Oncology, IRCCS-National Cancer Institute, Aviano, Italy.
authors.forename: Gianmaria
authors.initials: G
authors.lastname: Miolo
authors.affiliation: Department of Translational Research, IRCCS-National Cancer Institute, Aviano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Muraro
authors.affiliation: Department of Pharmacological and Bimolecular Science, University of Milan, Milan, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Caruso
authors.affiliation: Department of Medical Oncology, IRCCS-National Cancer Institute, Aviano, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Crivellari
authors.affiliation: Department of Biological Chemistry, Norwich Research Park, Norwich, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Ash
authors.affiliation: Department of Medical Oncology, IRCCS-National Cancer Institute, Aviano, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Scalone
authors.affiliation: Department of Medical Oncology, IRCCS-National Cancer Institute, Aviano, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Lombardi
authors.affiliation: Department of Translational Research, IRCCS-National Cancer Institute, Aviano, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Rizzolio
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Translational Research, IRCCS-National Cancer Institute, Aviano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Corona
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000627:therapeutic use*; D010597:Pharmacogenetics; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D013095:Spermidine / Q000097:blood*; D053719:Tandem Mass Spectrometry; D000068878:Trastuzumab / Q000627:therapeutic use*; D016896:Treatment Outcome; D014364:Tryptophan / Q000097:blood*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D013095:Spermidine; D000068878:Trastuzumab; D014364:Tryptophan; C508053:ERBB2 protein, human
keywords: breast; cancer; metabolomics; pharmacometabolomics; pharmacometabonomics