Breast Cancer Research and Treatment

, Volume 130, Issue 3, pp 845–854 | Cite as

Baseline diastolic dysfunction as a predictive factor of trastuzumab-mediated cardiotoxicity after adjuvant anthracycline therapy in breast cancer

  • Alexandre CochetEmail author
  • Gaetan Quilichini
  • Inna Dygai-Cochet
  • Claude Touzery
  • Michel Toubeau
  • Alina Berriolo-Riedinger
  • Bruno Coudert
  • Yves Cottin
  • Pierre Fumoleau
  • François Brunotte
Clinical trial


To evaluate the interest in assessing left ventricular diastolic function at baseline for prediction of trastuzumab-mediated cardiotoxicity (TMC) in the setting of adjuvant treatment for breast cancer. The study included 118 women presenting with HER2-positive early-stage invasive breast cancer. Patients received trastuzumab therapy over 1 year, concurrent with six cycles of docetaxel (n = 53), or following anthracycline-based chemotherapy with a cumulative dose of 300 mg/m2 (n = 45) or 600 mg/m2 (n = 20) of epirubicine. RNA was performed before anthracycline-based chemotherapy, before trastuzumab treatment (baseline), and every 3 months during treatment. Left ventricular ejection fraction (LVEF) and peak ejection rate (PER) were calculated to evaluate LV systolic function; peak filling rate (PFR), and time to peak filling rate (TPFR) were also calculated to evaluate LV diastolic function. Eighteen patients (15%) developed grade 1 or 2 TMC during follow-up. No significant difference was observed for age, cardiovascular risk factors, fasting blood glucose level, heart rate, systolic blood pressure, baseline LVEF, PER, and PFR between patients with and without TMC. In contrast, patients with TMC showed a longer TPFR at baseline (median [Q1–Q3]: 165 ms [149–190] vs. 142 ms [130–162]; P < 0.001). Furthermore, by logistic regression analysis, baseline TPFR >180 ms and the cumulative dose of epirubicin remained independent predictors of TMC. Patients receiving 600 mg/m2 of epirubicin before trastuzumab showed a higher incidence of TMC (35%) than did both patients who previously received 300 mg/m2 of epirubicin (13%) and those who received only docetaxel associated with trastuzumab (9%). Impaired left ventricular diastolic function before treatment is an independent predictor of trastuzumab-mediated cardiotoxicity. The evaluation of diastolic function could allow optimal risk stratification before the introduction of trastuzumab.


Breast cancer Trastuzumab-mediated cardiotoxicity Radionuclide angiocardiography Diastolic function 



This study is part of the Pharmimage® project. The authors thank Paul M. Walker and Philip Bastable for their assistance in the preparation of the manuscript.

Conflict of interest

BC: consultant for Roche, AstraZeneca, Sanofi-Aventis. PF: consultant for Sanofi-Aventis, Roche, GlaxoSmithKline. The other authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Alexandre Cochet
    • 1
    • 2
    Email author
  • Gaetan Quilichini
    • 1
  • Inna Dygai-Cochet
    • 1
  • Claude Touzery
    • 1
  • Michel Toubeau
    • 1
  • Alina Berriolo-Riedinger
    • 1
  • Bruno Coudert
    • 3
  • Yves Cottin
    • 4
  • Pierre Fumoleau
    • 3
  • François Brunotte
    • 1
    • 2
  1. 1.Nuclear Medicine DepartmentCentre Georges-François LeclercDijon CedexFrance
  2. 2.LE2i CNRS UMR 5158DijonFrance
  3. 3.Oncology DepartmentCentre Georges-François LeclercDijon CedexFrance
  4. 4.Cardiology DepartmentCHU Le BocageDijonFrance

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