Cardiovascular Toxicology

, Volume 12, Issue 2, pp 135–142

Prediction of Anthracycline Cardiotoxicity after Chemotherapy by Biomarkers Kinetic Analysis

  • Ornella Garrone
  • Nicola Crosetto
  • Cristiana Lo Nigro
  • Tiziana Catzeddu
  • Daniela Vivenza
  • Martino Monteverde
  • Marco Merlano
  • Mauro Feola


Anthracyclines are active drugs against breast cancer, but can exert cardiotoxic effects. We analyzed the association between the kinetics of various biomarkers during chemotherapy, and the risk of subsequent cardiac toxicity. 50 patients (49 women) with early breast cancer surgically treated and eligible to anthracycline-based adjuvant chemotherapy were analyzed. The left ventricular ejection fraction (LVEF) together with the plasma concentration of several blood markers was measured at the beginning of anthracycline chemotherapy (t0), 5 months (t1), 16 months (t2), 28 months (t3), and 40 months later (t4). A single measured LVEF value less than 50% or a clinically overt congestive heart failure (CHF) was considered cardiotoxic effects. We tested whether the kinetics of LVEF and blood biomarkers measured during chemotherapy was predictive of subsequent cardiotoxicity and overall cardiac fitness. The left ventricular ejection fraction measured at the end of treatment as well as the rate of change of hemoglobin concentration during anthracycline-based chemotherapy predicted cardiotoxicity in a 3-year follow-up period. When LVEF at the end of chemotherapy was lower than 53% or hemoglobin blood concentration declined more than 0.33 g/dL/month during chemotherapy, the odds ratio of subsequent cardiotoxicity was 37.3 and 18, respectively. The specificity of these two tests was 93.3% and 80%, whereas the sensitivity was 90.9 and 81.2%, respectively. Testing the rate of change of hemoglobin concentration during anthracycline-based chemotherapy, as well as the left ventricular ejection fraction at the end of treatment, seems a powerful method to assess the effects of anthracyclines on cardiac fitness and identify patients at high risk of CHF. Further validation of these tests on a large cohort of patients and cost-benefit analysis should be encouraged.


Anthracycline cardiotoxicity Breast cancer Biomarkers 

Supplementary material

12012_2011_9149_MOESM1_ESM.tif (111 kb)
Supplementary figure 1: representative kinetic profiles of LVEF for 3 out of the 41 cases in which LVEF was measured at each time point during follow-up. Red lines indicate the 50% cut-off LVEF value. (TIFF 111 kb)
12012_2011_9149_MOESM2_ESM.tif (183 kb)
Supplementary figure 2: average kinetic profiles of several blood biomarkers. P-values summarize the results of unpaired t tests comparing the distributions indicated by horizontal square brackets. WBC: white blood cells count. (TIFF 182 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ornella Garrone
    • 1
  • Nicola Crosetto
    • 3
  • Cristiana Lo Nigro
    • 2
  • Tiziana Catzeddu
    • 1
  • Daniela Vivenza
    • 2
  • Martino Monteverde
    • 2
  • Marco Merlano
    • 1
  • Mauro Feola
    • 4
  1. 1.Medical Oncology, Oncology DivisionS. Croce General HospitalCuneoItaly
  2. 2.Laboratory of Cancer Genetics and Translational Oncology, Oncology DivisionS. Croce General HospitalCuneoItaly
  3. 3.Department of BiologyMassachusetts Institute of TechnologyCambridgeUSA
  4. 4.Cardiovascular Rehabilitation-Heart Failure UnitOspedale SS TrinitàFossanoItaly

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