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dc.contributor.authorPutt, M.
dc.contributor.authorHahn, V. S.
dc.contributor.authorJanuzzi, James Louis
dc.contributor.authorSawaya, H.
dc.contributor.authorSebag, I. A.
dc.contributor.authorPlana, J. C.
dc.contributor.authorPicard, Michael Howard
dc.contributor.authorCarver, J. R.
dc.contributor.authorHalpern, E
dc.contributor.authorKuter, Irene
dc.contributor.authorPasseri, Jonathan James
dc.contributor.authorCohen, V.
dc.contributor.authorBanchs, J.
dc.contributor.authorMartin, R. P.
dc.contributor.authorGerszten, Robert Edgardo
dc.contributor.authorScherrer-Crosbie, Marielle
dc.contributor.authorKy, B.
dc.date.accessioned2016-10-19T18:24:34Z
dc.date.issued2015
dc.identifier.citationPutt, M., V. S. Hahn, J. L. Januzzi, H. Sawaya, I. A. Sebag, J. C. Plana, M. H. Picard, et al. 2015. “Longitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumab.” Clinical Chemistry 61 (9) (July 27): 1164–1172. doi:10.1373/clinchem.2015.241232.en_US
dc.identifier.issn0009-9147en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29048880
dc.description.abstractBACKGROUND: Biomarkers may play an important role in identifying patients at risk for cancer therapy cardiotoxicity. Our objectives were to define the patterns of change in biomarkers with cancer therapy and their associations with cardiotoxicity. METHODS: In a multicenter cohort of 78 breast cancer patients undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at baseline and every 3 months over a maximum follow-up of 15 months. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hsCRP), N-terminal pro–B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and galectin 3 (gal-3). We determined if biomarker increases were associated with cardiotoxicity at the same visit and the subsequent visit over the entire course of therapy. Cardiotoxicity was defined by the Cardiac Review and Evaluation Criteria; alternative definitions were also considered. RESULTS: Across the entire cohort, all biomarkers except NT-proBNP and gal-3 demonstrated increases by 3 months; these increases persisted for GDF-15, PlGF, and hs-cTnI at 15 months. Increases in MPO, PlGF, and GDF-15 were associated with cardiotoxicity at the same visit [MPO hazard ratio 1.38 (95% CI 1.10–1.71), P = 0.02; PlGF 3.78 (1.30–11.0), P = 0.047; GDF-15 1.71 (1.15–2.55), P = 0.01] and the subsequent visit. MPO was robust to alternative outcome definitions. CONCLUSIONS: Increases in MPO are associated with cardiotoxicity over the entire course of doxorubicin and trastuzumab therapy. Assessment with PlGF and GDF-15 may also be of value. These findings motivate validation studies in additional cohorts.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Association for Clinical Chemistry (AACC)en_US
dc.relation.isversionofdoi:10.1373/clinchem.2015.241232en_US
dc.relation.hasversionhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667170/en_US
dash.licenseOAP
dc.titleLongitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumaben_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalClinical Chemistryen_US
dash.depositing.authorPicard, Michael Howard
dc.date.available2016-10-19T18:24:34Z
dc.identifier.doi10.1373/clinchem.2015.241232*
dash.authorsorderedfalse
dash.contributor.affiliatedKuter, Irene
dash.contributor.affiliatedJanuzzi, James
dash.contributor.affiliatedHalpern, Elkan F.
dash.contributor.affiliatedGerszten, Robert
dash.contributor.affiliatedPicard, Michael
dash.contributor.affiliatedPasseri, Jonathan
dash.contributor.affiliatedScherrer-Crosbie, Marielle


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