Sympathetic nervous system alterations with HER2+ antagonism: an early marker of cardiac dysfunction with breast cancer treatment?
Publication/Presentation Date
1-1-2014
Abstract
BACKGROUND: HER2 antagonists (anti-HER2; e.g., trastuzumab and lapatinib) are effective in treating an aggressive form of breast cancer (BC), but can cause cardiotoxicity due to the disruption in neuregulin (NRG)/HER2+ ligand receptor signalling. The recent data show that NRG-HER2 receptors located in the medulla oblongata are important regulators of vasomotor tone. Disrupting the NRG-HER2 signalling in mouse medulla results in increased sympathetic nerve output and blood pressure. We hypothesized that anti-HER2 agents would cause increased sympathetic tone with changes in plasma catecholamines and NRG.
METHODS: In 15 newly diagnosed HER2+ BC patients receiving anti-HER2 agents, vital signs were measured along with supine plasma epinephrine (EPI), norepinephrine (NE), and NRG at baseline and three months. Serial echocardiography was performed.
RESULTS: With three months of anti-HER2 treatment, NE increased (2.334 ± 1.294 nmol/L vs. 3.262 ± 2.103 nmol/L; p = 0.004) and NRG decreased (12.7±15.7 ng/ml vs. 10.9 ± 13.3 ng/ml; p = 0.036) with a corresponding increase in systolic blood pressure (110 ± 10 mmHg vs. 120 ± 16 mmHg, p = 0.049) and diastolic blood pressure (67 ± 14 vs. 77 ± 10, p = 0.009). There was no change, however, in EPI (0.183 ± 0.151 nmol/L vs. 0.159 ± 0.174 nmol/L; p = 0.519) or heart rate (73 ± 12 bpm vs. 77 ± 10 bpm, p = 0.146). Left ventricular ejection function declined over the follow-up period (baseline 63 ± 6% vs. follow-up 56 ± 5%).
CONCLUSIONS: Anti-HER2 treatment results in increased NE, blood pressure, and decreased NRG; this suggests that the inhibition of NRGHER2 signalling leads to increased sympathoneural tone. Larger studies are needed to determine if these observations have prognostic value and may be offset with medical interventions, such as beta-blockers.
CLINICAL TRIAL REGISTRATION: The study was registered with www.clinicaltrials.gov (NCT00875238).
Volume
8
First Page
446
Last Page
446
ISSN
1754-6605
Published In/Presented At
Lenneman, C. G., Abdallah, W. M., Smith, H. M., Abramson, V., Mayer, I. A., Silverstein, C., Silverstein, C., Means-Powell, J., Paranjape, S. Y., Lenihan, D., Sawyer, D. B., & Raj, S. R. (2014). Sympathetic nervous system alterations with HER2+ antagonism: an early marker of cardiac dysfunction with breast cancer treatment?. Ecancermedicalscience, 8, 446. https://doi.org/10.3332/ecancer.2014.446
Disciplines
Medicine and Health Sciences
PubMedID
25114718
Department(s)
Department of Medicine
Document Type
Article