Cardiotoxicity and Cardiovascular Biomarkers in Patients With Breast Cancer: Data From the GeparOcto-GBG 84 Trial.

Abstract

Background Patients with breast cancer can be affected by cardiotoxic reactions through cancer therapies. Cardiac biomarkers, like NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T, might have predictive value. Methods and Results Echocardiography, ECG, hemodynamic parameters, NT-proBNP and high-sensitivity cardiac troponin T were assessed in 853 patients with early-stage breast cancer randomized in the German Breast Group GeparOcto-GBG 84 phase III trial. Patients received neo-adjuvant dose-dense, dose-intensified epirubicin, paclitaxel, and cyclophosphamide (iddEPC group, n=424) or paclitaxel, non-pegylated doxorubicin, and in triple negative breast cancer, (paclitaxel, non-pegylated doxorubicin, carboplatin group, n=429) treatment for 18 weeks. Patients positive for human epidermal growth receptor 2 (n=354, 41.5%) received monoclonal antibodies on top of allocated therapy; 119 (12.9%) of all patients showed a cardiotoxic reaction during therapy (15 [1.8%] using a more strict definition). Presence of cardiotoxic reactions was irrespective of treatment allocation (P=0.31). Small but significant increases in NT-proBNP developed early in patients with a cardiotoxic reaction as compared with those without in whom NT-proBNP rose only towards the end of therapy (P=0.04). High-sensitivity cardiac troponin T rose early in both groups. Logistic regression showed that NT-proBNP (odds ratio [OR], 1.03; 95% CI, 1.008-1.055; P=0.01) and hemoglobin (OR, 1.31; 95% CI, 1.05-1.63; P=0.02) measured at 6 weeks after treatment initiation were significantly associated with cardiotoxic reactions. Conclusions NT-proBNP and hemoglobin are significantly associated with cardiotoxic reactions in patients with early-stage breast cancer undergoing dose-dense and dose-intensified chemotherapy, but high-sensitivity cardiac troponin T is not. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT02125344.

• Authors: Alexandra Maria Rüger, Andreas Schneeweiss, Sabine Seiler, Hans Tesch, Marion van Mackelenbergh, Frederik Marmé, Kristina Lübbe, Bruno Sinn, Thomas Karn, Elmar Stickeler, Volkmar Müller, Christian Schem, Carsten Denkert, Peter A Fasching, Valentina Nekljudova, Tania Garfias-Macedo, Gerd Hasenfuß, Wilhelm Haverkamp, Sibylle Loibl, Stephan von Haehling
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 9 Issue 23 Pg. e018143 (12 2020) ISSN: 2047-9980 [Electronic] England
• PMID: 33191846 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers
• Peptide Fragments
• Troponin T
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain

Topics

• Adult
• Antineoplastic Agents (adverse effects)
• Biomarkers (blood)
• Breast Neoplasms (blood, drug therapy)
• Cardiotoxicity (blood, diagnosis, epidemiology)
• Cohort Studies
• Echocardiography
• Female
• Germany
• Humans
• Logistic Models
• Middle Aged
• Natriuretic Peptide, Brain (blood)
• Odds Ratio
• Peptide Fragments (blood)
• Prevalence
• Risk Factors
• Stroke Volume
• Troponin T (blood)