Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Variations of circulating cardiac biomarkers during and after anthracycline-containing chemotherapy in breast cancer patients

Authors: Pierre Frères, Nassim Bouznad, Laurence Servais, Claire Josse, Stéphane Wenric, Aurélie Poncin, Jérôme Thiry, Marie Moonen, Cécile Oury, Patrizio Lancellotti, Vincent Bours, Guy Jerusalem

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

Over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment options. However, oncologists are concerned by the risk of long term treatment side effects, including congestive heart failure (CHF).

Methods

In this study, we evaluated innovative circulating cardiac biomarkers during and after anthracycline-based neoadjuvant chemotherapy (NAC) in breast cancer patients. Levels of cardiac-specific troponins T (cTnT), N-terminal natriuretic peptides (NT-proBNP), soluble ST2 (sST2) and 10 circulating microRNAs (miRNAs) were measured.

Results

Under chemotherapy, we observed an elevation of cTnT and NT-proBNP levels, but also the upregulation of sST2 and of 4 CHF-related miRNAs (miR-126-3p, miR-199a-3p, miR-423-5p, miR-34a-5p). The elevations of cTnT, NT-proBNP, sST2 and CHF-related miRNAs were poorly correlated, suggesting that these molecules could provide different information.

Conclusions

Circulating miRNA and sST2 are potential biomarkers of the chemotherapy-related cardiac dysfunction (CRCD). Nevertheless, further studies and long-term follow-up are needed in order to evaluate if these new markers may help to predict CRCD and to identify the patients at risk to later develop CHF.
Appendix
Available only for authorised users
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed
2.
Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355(15):1572–82.CrossRefPubMed
3.
Mertens AC, Yasui Y, Neglia JP, Potter JD, Nesbit ME Jr, Ruccione K, et al. Late mortality experience in five-year survivors of childhood and adolescent cancer: the childhood cancer survivor study. J Clin Oncol. 2001;19:3163–72.CrossRefPubMed
4.
Diller L, Chow EJ, Gurney JG, Hudson MM, Kadin-Lottick NS, Kawashima TI, et al. Chronic disease in the childhood cancer survivor study cohort: a review of published findings. J Clin Oncol. 2009;27:2339–55.CrossRefPubMedPubMedCentral
5.
Carver JR, Shapiro CL, Ng A, Jacobs L, Schwartz C, Virgo KS, et al. American Society of Clinical Oncology clinical evidence review on the ongoing Care of Adult Cancer Survivors: cardiac and pulmonary late effects. J Clin Oncol. 2007;25:3991–4008.CrossRefPubMed
6.
Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004;109:2749–54.CrossRefPubMed
7.
Gerhardt W, Katus H, Ravkilde J, Hamm C, Jørgensen PJ, Peheim E, et al. S-troponin T in suspected ischemic myocardial injury compared with mass and catalytic concentrations of S-creatine kinase isoenzyme MB. Clin Chem. 1991;37:1405–11.PubMed
8.
Cil T, Kaplan AM, Altintas A, Akin AM, Alan S, Isikdogan A. Use of N-terminal pro-brain natriuretic peptide to assess left ventricular function after adjuvant doxorubicin therapy in early breast cancer patients: a prospective series. Clin Drug Investig. 2009;29(2):131–7.CrossRefPubMed
9.
Kittiwarawut A, Vorasettakarnkij Y, Tanasanvimon S, Manasnayakorn S, Sriuranpong V. Serum NT-proBNP in the early detection of doxorubicin-induced cardiac dysfunction. Asia Pac J Clin Oncol. 2013;9(2):155–61.CrossRefPubMed
10.
Ky B, Putt M, Sawaya H, French B, Januzzi JL Jr, Sebag IA, et al. Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol. 2014;63(8):809–16.CrossRefPubMed
11.
De Iuliis F, Salerno G, Taglieri L, De Biase L, Lanza R, Cardelli P, Scarpa S. Serum biomarkers evaluation to predict chemotherapy-induced cardiotoxicity in breast cancer patients. Tumour Biol. 2016;37(3):3379–87.CrossRefPubMed
12.
Vogelsang TW, Jensen RJ, Hesse B, Kjær A. BNP cannot replace gated equilibrium radionuclide ventriculography in monitoring of anthracycline-induced cardiotoxity. Int J Cardiol. 2008;124:193–7.CrossRefPubMed
13.
Daugaard G, Lassen U, Bie P, Pedersen EB, Jensen KT, Abildgaard U, et al. Natriuretic peptides in the monitoring of anthracycline induced reduction in left ventricular ejection fraction. Eur J Heart Fail. 2005;7:87–93.CrossRefPubMed
14.
Weinberg EO, Shimpo M, Hurwitz S, Tominaga S-I, Rouleau J-L, Lee RT. Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation. 2003;107:721–6.CrossRefPubMed
15.
Pascual-Figal DA, Ordoñez-Llanos J, Tornel PL, Vázquez R, Puig T, Valdés M, et al. Soluble ST2 for predicting sudden cardiac death in patients with chronic heart failure and left ventricular systolic dysfunction. J Am Coll Cardiol. 2009;54(23):2174–9.CrossRefPubMed
16.
Gruson D, Lepoutre T, Ahn SA, Rousseau MF. Increased soluble ST2 is a stronger predictor of long-term cardiovascular death than natriuretic peptides in heart failure patients with reduced ejection fraction. Int J Cardiol. 2014;172(1):e250–2.CrossRefPubMed
17.
Coglianese EE, Larson MG, Vasan RS, Ho JE, Ghorbani A, McCabe EL, et al. Distribution and clinical correlates of the interleukin receptor family member soluble ST2 in the Framingham Heart Study. Clin Chem. 2012;58:1673–81.CrossRefPubMedPubMedCentral
18.
Sandhu H, Maddock H. Molecular basis of cancer-therapy-induced cardiotoxicity: introducing microRNA biomarkers for early assessment of subclinical myocardial injury. Clin Sci. 2014;126:377–400.CrossRefPubMed
19.
Horie T, Ono K, Nishi H, Nagao K, Kinoshita M, Watanabe S, et al. Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway. Cardiovasc Res. 2010;87:656–64.CrossRefPubMedPubMedCentral
20.
Desai VG, C Kwekel J, Vijay V, Moland CL, Herman EH, Lee T, et al. Early biomarkers of doxorubicin-induced heart injury in a mouse model. Toxicol Appl Pharmacol. 2014;281:221–9.CrossRefPubMed
21.
Nishimura Y, Kondo C, Morikawa Y, Tonomura Y, Torii M, Yamate J, Uehara T. Plasma miR-208 as a useful biomarker for drug-induced cardiotoxicity in rats. J Appl Toxicol. 2015;35:173–80.CrossRefPubMed
22.
Vacchi-Suzzi C, Bauer Y, Berridge BR, Bongiovanni S, Gerrish K, Hamadeh HK, et al. Perturbation of microRNAs in rat heart during chronic doxorubicin treatment. PLoS One. 2012;7:e40395.CrossRefPubMedPubMedCentral
23.
Frères P, Josse C, Bovy N, Boukerroucha M, Struman I, Bours V, Jerusalem G. Neoadjuvant chemotherapy in breast cancer patients induces miR-34a and miR-122 expression. J Cell Physiol. 2015;230:473–81.CrossRefPubMed
24.
Frères P, Wenric S, Boukerroucha M, Fasquelle C, Thiry J, Bovy N, et al. Circulating microRNA-based screening tool for breast cancer. Oncotarget. 2016;7:5416–28.CrossRefPubMed
25.
D'Alessandra Y, Devanna P, Limana F, Straino S, Di Carlo A, Brambilla PG, et al. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J. 2010;31:2765–73.CrossRefPubMedPubMedCentral
26.
Akat KM, Moore-McGriff D, Morozov P, Brown M, Gogakos T, Da Rosa JC, et al. Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers. PNAS. 2014;111:11151–6.CrossRefPubMedPubMedCentral
27.
Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE, Pinto YM. MiR423-5p as a circulating biomarker for heart failure. Circ Res. 2010;106:1035–9.CrossRefPubMed
28.
Fukushima Y, Nakanishi M, Nonogi H, Goto Y, Iwai N. Assessment of plasma miRNAs in congestive heart failure. Circ J. 2011;75:336–40.CrossRefPubMed
29.
Boon RA, Iekushi K, Lechner S, Seeger T, Fischer A, Heydt S, et al. MicroRNA-34a regulates cardiac ageing and function. Nature. 2013;495:107–10.CrossRefPubMed
30.
Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009;55(4):611–22.CrossRefPubMed
31.
Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010;50(4):298–301.CrossRefPubMedPubMedCentral
32.
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3:1101–8.CrossRefPubMed
33.
Mestdagh P, Van Vlierberghe P, De Weer A, Muth D, Westermann F, Speleman F, Vandesompele J. A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol. 2009;10(6):R64.CrossRefPubMedPubMedCentral
34.
Ganz WI, Sridhar KS, Forness TJ. Detection of early anthracycline cardiotoxicity by monitoring the peak filling rate. Am J Clin Oncol. 1993;16(2):109–12.CrossRefPubMed
35.
Ewer MS, Vooletich MT, Durand JB, Woods ML, Davis JR, Valero V, Lenihan DJ. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol. 2005;23(31):7820–6.CrossRefPubMed
36.
37.
Gillibert-Duplantier J, Duthey B, Sisirak V, Salaün D, Gargi T, Trédan O, et al. Gene expression profiling identifies sST2 as an effector of ErbB2-driven breast carcinoma cell motility, associated with metastasis. Oncogene. 2012;31:3516–24.CrossRefPubMed
38.
Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, et al. Circulating microRNAs in patients with coronary artery disease novelty and significance. Circ Res. 2010;107:677–84.CrossRefPubMed
39.
Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15:261–71.CrossRefPubMedPubMedCentral
40.
Luengo-Gil G, González-Billalabeitia E, Chaves-Benito A, Martínez EG, Garre EG, Vicente V, la Peña de FA. Effects of conventional neoadjuvant chemotherapy for breast cancer on tumor angiogenesis. Breast Cancer Res Treat. 2015;151:577–87.CrossRefPubMed
41.
Ovchinnikova ES, Schmitter D, Vegter EL, Maaten ter JM, Valente MAE, Liu LCY, et al. Signature of circulating microRNAs in patients with acute heart failure. Eur J Heart Fail. 2016;18:414–23.CrossRefPubMed
42.
Song XW, Li Q, Lin L, Wang XC, Li DF, Wang GK, et al. MicroRNAs are dynamically regulated in hypertrophic hearts, and miR-199a is essential for the maintenance of cell size in cardiomyocytes. J Cell Physiol. 2010;225:437–43.CrossRefPubMed
43.
Eulalio A, Mano M, Ferro MD, Zentilin L, Sinagra G, Zacchigna S, Giacca M. Functional screening identifies miRNAs inducing cardiac regeneration. Nature. 2012;492:376–81.CrossRefPubMed
44.
Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail. 2012;14:147–54.CrossRefPubMed
45.
Seronde MF, Vausort M, Gayat E, Goretti E, Ng LL, Squire IB, et al. Circulating microRNAs and outcome in patients with acute heart failure. PLoS One. 2015;10:e0142237.CrossRefPubMedPubMedCentral
46.
47.
48.
Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, et al. p53 status and the efficacy of cancer therapy in vivo. Science. 1994;266(5186):807–10.CrossRefPubMed
Metadata
Title
Variations of circulating cardiac biomarkers during and after anthracycline-containing chemotherapy in breast cancer patients
Authors
Pierre Frères
Nassim Bouznad
Laurence Servais
Claire Josse
Stéphane Wenric
Aurélie Poncin
Jérôme Thiry
Marie Moonen
Cécile Oury
Patrizio Lancellotti
Vincent Bours
Guy Jerusalem
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4015-4

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Research article

The feasibility, acceptability and outcomes of exergaming among individuals with cancer: a systematic review

Research article

A prospective cohort examination of haematological parameters in relation to cancer death and incidence: the Busselton Health Study

Study protocol

The PANDA study: a randomized phase II study of first-line FOLFOX plus panitumumab versus 5FU plus panitumumab in RAS and BRAF wild-type elderly metastatic colorectal cancer patients

Research article

HPV-16 E7 expression up-regulates phospholipase D activity and promotes rapamycin resistance in a pRB-dependent manner

Research article

The preoperative prognostic nutritional index is a predictive and prognostic factor of high-grade serous ovarian cancer

Case report

Unusual bilateral ovarian metastases from ileal gastrointestinal stromal tumor (GIST): a case report
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits