Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study
BackgroundAnthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change...
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| Format: | Article |
| Language: | English |
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Wiley
2017-11-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.117.006513 |
| _version_ | 1819183271618019328 |
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| author | Geeta Gulati Siri L. Heck Helge Røsjø Anne H. Ree Pavel Hoffmann Tor‐Arne Hagve Jon Norseth Berit Gravdehaug Kjetil Steine Jürgen Geisler Torbjørn Omland |
| author_facet | Geeta Gulati Siri L. Heck Helge Røsjø Anne H. Ree Pavel Hoffmann Tor‐Arne Hagve Jon Norseth Berit Gravdehaug Kjetil Steine Jürgen Geisler Torbjørn Omland |
| author_sort | Geeta Gulati |
| collection | DOAJ |
| description | BackgroundAnthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on‐treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines. Methods and ResultsThis report encompasses 121 women included in the 2×2 factorial, placebo‐controlled, double‐blind PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial with metoprolol and candesartan given concomitantly with anticancer therapy containing the anthracycline, epirubicin (total cumulative dose, 240–400 mg/m2). Cardiovascular magnetic resonance, echocardiography images, and circulating levels of biomarkers were obtained before and after anthracycline treatment. Cardiac troponins I and T, B‐type natriuretic peptide, N‐terminal pro‐B‐type natriuretic peptide, C‐reactive protein, and galectin‐3 increased during anthracycline therapy (all P<0.05). The troponin response was attenuated by metoprolol (P<0.05), but not candesartan. There was no association between change in biomarker concentrations and change in cardiac function during anthracycline therapy. ConclusionsTreatment with contemporary anthracycline doses for early breast cancer is associated with increase in circulating cardiovascular biomarkers. This increase is, however, not associated with early decline in ventricular function. Beta‐blockade may attenuate early myocardial injury, but whether this attenuation translates into reduced risk of developing ventricular dysfunction in the long term remains unclear. Clinical Trial RegistrationURL: http://www.clinicaltrial.gov. Unique identifier: NCT01434134. |
| first_indexed | 2024-12-22T22:59:22Z |
| format | Article |
| id | doaj.art-fa4d943f76444ab399489cb7d2481be1 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-22T22:59:22Z |
| publishDate | 2017-11-01 |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-fa4d943f76444ab399489cb7d2481be12022-12-21T18:09:44ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802017-11-0161110.1161/JAHA.117.006513Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) StudyGeeta Gulati0Siri L. Heck1Helge Røsjø2Anne H. Ree3Pavel Hoffmann4Tor‐Arne Hagve5Jon Norseth6Berit Gravdehaug7Kjetil Steine8Jürgen Geisler9Torbjørn Omland10Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, NorwayDepartment of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, NorwayDepartment of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, NorwayDepartment of Oncology, Division of Medicine, Akershus University Hospital, Lørenskog, NorwayDepartment of Cardiology, Division of Cardiovascular and Pulmonary Diseases, Oslo University Hospital, Ullevål, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, NorwayClinic for Medical Diagnostics, Vestre Viken Hospital Trust, Drammen, NorwayDepartment of Breast and Endocrine Surgery, Division of Surgery, Akershus University Hospital, Lørenskog, NorwayDepartment of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, NorwayDepartment of Oncology, Division of Medicine, Akershus University Hospital, Lørenskog, NorwayDepartment of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, NorwayBackgroundAnthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on‐treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines. Methods and ResultsThis report encompasses 121 women included in the 2×2 factorial, placebo‐controlled, double‐blind PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial with metoprolol and candesartan given concomitantly with anticancer therapy containing the anthracycline, epirubicin (total cumulative dose, 240–400 mg/m2). Cardiovascular magnetic resonance, echocardiography images, and circulating levels of biomarkers were obtained before and after anthracycline treatment. Cardiac troponins I and T, B‐type natriuretic peptide, N‐terminal pro‐B‐type natriuretic peptide, C‐reactive protein, and galectin‐3 increased during anthracycline therapy (all P<0.05). The troponin response was attenuated by metoprolol (P<0.05), but not candesartan. There was no association between change in biomarker concentrations and change in cardiac function during anthracycline therapy. ConclusionsTreatment with contemporary anthracycline doses for early breast cancer is associated with increase in circulating cardiovascular biomarkers. This increase is, however, not associated with early decline in ventricular function. Beta‐blockade may attenuate early myocardial injury, but whether this attenuation translates into reduced risk of developing ventricular dysfunction in the long term remains unclear. Clinical Trial RegistrationURL: http://www.clinicaltrial.gov. Unique identifier: NCT01434134.https://www.ahajournals.org/doi/10.1161/JAHA.117.006513beta‐blockerbrain natriuretic peptidecardio‐oncologyC‐reactive proteinmagnetic resonance imagingtroponin |
| spellingShingle | Geeta Gulati Siri L. Heck Helge Røsjø Anne H. Ree Pavel Hoffmann Tor‐Arne Hagve Jon Norseth Berit Gravdehaug Kjetil Steine Jürgen Geisler Torbjørn Omland Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease beta‐blocker brain natriuretic peptide cardio‐oncology C‐reactive protein magnetic resonance imaging troponin |
| title | Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study |
| title_full | Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study |
| title_fullStr | Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study |
| title_full_unstemmed | Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study |
| title_short | Neurohormonal Blockade and Circulating Cardiovascular Biomarkers During Anthracycline Therapy in Breast Cancer Patients: Results From the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) Study |
| title_sort | neurohormonal blockade and circulating cardiovascular biomarkers during anthracycline therapy in breast cancer patients results from the prada prevention of cardiac dysfunction during adjuvant breast cancer therapy study |
| topic | beta‐blocker brain natriuretic peptide cardio‐oncology C‐reactive protein magnetic resonance imaging troponin |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.117.006513 |
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