title: Baseline diastolic dysfunction as a predictive factor of trastuzumab-mediated cardiotoxicity after adjuvant anthracycline therapy in breast cancer.
abstract: 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/m(2) (n = 45) or 600 mg/m(2) (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/m(2) of epirubicin before trastuzumab showed a higher incidence of TMC (35%) than did both patients who previously received 300 mg/m(2) 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.
authors.affiliation: Nuclear Medicine Department, Centre Georges-François Leclerc, 1, rue Professeur Marion, 21079 Dijon Cedex, France. acochet@cgfl.fr
authors.forename: Alexandre
authors.initials: A
authors.lastname: Cochet
authors.forename: Gaetan
authors.initials: G
authors.lastname: Quilichini
authors.forename: Inna
authors.initials: I
authors.lastname: Dygai-Cochet
authors.forename: Claude
authors.initials: C
authors.lastname: Touzery
authors.forename: Michel
authors.initials: M
authors.lastname: Toubeau
authors.forename: Alina
authors.initials: A
authors.lastname: Berriolo-Riedinger
authors.forename: Bruno
authors.initials: B
authors.lastname: Coudert
authors.forename: Yves
authors.initials: Y
authors.lastname: Cottin
authors.forename: Pierre
authors.initials: P
authors.lastname: Fumoleau
authors.forename: François
authors.initials: F
authors.lastname: Brunotte
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D015251:Epirubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011877:Radionuclide Imaging; D015203:Reproducibility of Results; D012307:Risk Factors; D000068878:Trastuzumab; D018754:Ventricular Dysfunction / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology
chemical_list: D018943:Anthracyclines; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015251:Epirubicin; D000068878:Trastuzumab