Dataset Information

Baseline Immunoglobulin E Levels as a Marker of Doxorubicin- and Trastuzumab-Associated Cardiac Dysfunction.

ABSTRACT: There is a critical need to develop robust, mechanistic strategies to identify patients at increased risk of cancer therapeutics-related cardiac dysfunction (CTRCD).We aimed to discover new biomarkers associated with doxorubicin- and trastuzumab-induced CTRCD using high-throughput proteomic profiling.Plasma, echocardiograms, and clinical outcomes were collected at standardized intervals in breast cancer patients undergoing doxorubicin and trastuzumab cancer therapy. Thirty-one longitudinal plasma samples from 3 cases with CTRCD and 4 age- and cancer-matched controls without CTRCD were processed and analyzed using label-free liquid chromatography-mass spectrometry. From these analyses, 862 proteins were identified from case/control pairs 1 and 2 and 1360 proteins from case/control pair 3. Proteins with a >1.5-fold change in cases compared with controls with a P<0.05 either at the time of CTRCD diagnosis or across all time points were considered candidate diagnostic or predictive biomarkers, respectively. The protein that demonstrated the largest differences between cases and controls was immunoglobulin E, with higher levels detected at baseline and across all time points in controls without CTRCD as compared with matched CTRCD cases (P<0.05). Similarly, in a validation study of 35 participants treated with doxorubicin and trastuzumab, high baseline immunoglobulin E levels were associated with a significantly lower risk of CTRCD (P=0.018).In patients receiving doxorubicin and trastuzumab, high baseline immunoglobulin E levels are associated with a lower risk of CTRCD. These novel findings suggest a new paradigm in cardio-oncology, implicating the immune system as a potential mediator of doxorubicin- and trastuzumab-induced cardiac dysfunction.

SUBMITTER: Beer LA

PROVIDER: S-EPMC5085891 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Baseline Immunoglobulin E Levels as a Marker of Doxorubicin- and Trastuzumab-Associated Cardiac Dysfunction.

Beer Lynn A LA Kossenkov Andrew V AV Liu Qin Q Luning Prak Eline E Domchek Susan S Speicher David W DW Ky Bonnie B

Circulation research 20160831 10

<h4>Rationale</h4>There is a critical need to develop robust, mechanistic strategies to identify patients at increased risk of cancer therapeutics-related cardiac dysfunction (CTRCD).<h4>Objective</h4>We aimed to discover new biomarkers associated with doxorubicin- and trastuzumab-induced CTRCD using high-throughput proteomic profiling.<h4>Methods and results</h4>Plasma, echocardiograms, and clinical outcomes were collected at standardized intervals in breast cancer patients undergoing doxorubic ...[more]

PMID: 27582370

Similar Datasets

Project description:BACKGROUND:We report cardiac events in the Persephone trial which compares 6-12 months of adjuvant trastuzumab in women with confirmed HER2-positive, early-stage breast cancer. METHODS:Clinical cardiac events were defined as any of the following: symptoms and/or signs of congestive heart failure (CHF) and new or altered CHF medication. In addition, left ventricular ejection fraction (LVEF) was measured at baseline and then 3 monthly for 12 months. RESULTS:A total of 2500 patients, aged 22-82, were included: 1251 randomised to 12 months and 1249 to 6 months of trastuzumab treatment. A total of 93% (2335/2500) received anthracyclines, 49% of these (1136/2335) with taxanes. Cardiotoxicity delayed treatment in 6% of 12-month and 4% of 6-month patients (P=0.01), and stopped treatment early in 8% (96/1214) of 12-month and 4% (45/1216) of 6-month patients (P<0.0001). Between 7 and 12 months, more 12-month than 6-month patients had LVEFs<50% (8% vs 5%; P=0.004). LVEFs showed quadratic change over time, and 6-month patients had a more rapid recovery (P=0.02). In a landmark analysis twice as many 12-month patients, free of cardiac events at 6 months, had cardiac problems in months 7-12 (6% (66/1046) vs 3% (29/1035) of 6-month patients (P=0.0002)). Lower baseline LVEF predicted more cardiac dysfunction in both arms (reference ?65%: 55 to <65% OR 1.61 (95% CI 1.26-2.04); <55% OR 5.22 (3.42-7.95)) as did increasing age (reference <50: 50-59 OR 1.58 (1.17-2.12), 60-69 OR 1.91 (1.42-2.57)) 70+ OR 2.72 (1.82-4.08)) and prior use of cardiac medication (OR 8.46 (4.69-15.25)). >3 cycles of anthracycline was associated with higher risk of cardiac events only for 12-month patients (OR 1.41 (1.04-1.90)), and not for 6-month patients (OR 1.28 (0.91-1.79)). CONCLUSIONS:We demonstrate significantly fewer cardiac events from 6 months of adjuvant trastuzumab compared with that from 12 months. This cardiac signal adds importance to the question of the optimum duration of adjuvant trastuzumab treatment. If 6 months is proven to have non-inferior outcomes to 12 months treatment, these data would support 6 months as the standard of care.

Dataset Information

Baseline Immunoglobulin E Levels as a Marker of Doxorubicin- and Trastuzumab-Associated Cardiac Dysfunction.

Publications

Baseline Immunoglobulin E Levels as a Marker of Doxorubicin- and Trastuzumab-Associated Cardiac Dysfunction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets