N-terminal pro-B-type natriuretic peptide plasma levels as a potential biomarker for cardiac damage after radiotherapy in patients with left-sided breast cancer

Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):e239-46. doi: 10.1016/j.ijrobp.2011.03.058. Epub 2011 Jun 2.

Abstract

Purpose: Adjuvant radiotherapy (RT) after breast-conserving surgery has been associated with increased cardiovascular mortality. Cardiac biomarkers may aid in identifying patients with radiation-mediated cardiac dysfunction. We evaluated the correlation between N-terminal pro-B–type natriuretic peptide (NT-proBNP) and troponin (TnI) and the dose of radiation to the heart in patients with left-sided breast cancer.

Methods and materials: NT-proBNP and TnI plasma concentrations were measured in 30 left-sided breast cancer patients (median age, 55.0 years) 5 to 22 months after RT (Group I) and in 30 left-sided breast cancer patients (median age, 57.0 years) before RT as control group (Group II). Dosimetric and geometric parameters of heart and left ventricle were determined in all patients of Group I. Seventeen patients underwent complete two-dimensional echocardiography.

Results: NT-proBNP levels were significantly higher (p = 0.03) in Group I (median, 90.0 pg/ml; range, 16.7–333.1 pg/ml) than in Group II (median, 63.2 pg/ml; range, 11.0–172.5 pg/ml). TnI levels remained below the cutoff threshold of 0.07 ng/ml in both groups. In patients with NT-proBNP values above the upper limit of 125 pg/ml, there were significant correlations between plasma levels and V(3 Gy)(%) (p = 0.001), the ratios (p = 0.01), the ratios D(15 cm)(3)/D(50%) (Gy) (p = 0.008) for the heart and correlations between plasma levels and V(2 Gy) (%) (p = 0.002), the ratios (p = 0.03), and the ratios (p = 0.05) for the ventricle.

Conclusions: Patients with left-sided breast cancer show higher values of NT-pro BNP after RT when compared with non–RT-treated matched patients, increasing in correlation with high doses in small volumes of heart and ventricle. The findings of this study show that the most important parameters are not the mean doses but instead the small percentage of organ volumes (heart or ventricle) receiving high dose levels, supporting the notion that the heart behaves as a serial organ.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anthracyclines / therapeutic use
  • Biomarkers / blood
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • Case-Control Studies
  • Echocardiography / methods
  • Female
  • Heart / diagnostic imaging
  • Heart / radiation effects*
  • Heart Ventricles / radiation effects
  • Humans
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Organs at Risk / radiation effects
  • Peptide Fragments / blood*
  • Radiation Dosage
  • Radiation Injuries / blood*
  • Tomography, X-Ray Computed
  • Troponin I / blood*

Substances

  • Anthracyclines
  • Biomarkers
  • Peptide Fragments
  • Troponin I
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain