Abstract 374: Predictive Factors of Trastuzumab Mediated Cardiotoxicity in the Setting of Adjuvant Chemotherapy for Breast Cancer: Analysis of the Baseline Left Ventricular Diastolic Function Using Radionuclide Angiocardiography
Background: Trastuzumab (TZM) has been shown to benefit patients with HER2-positive breast cancer, alone or in combination with chemotherapy, but can induce cardiotoxicity.
Aim: to evaluate the interest of left ventricular diastolic function before any treatment, analyzed by Radionuclide Angiocardiography (RNA), to predict TZM cardiotoxicity in the setting of adjuvant treatment of early-stage invasive breast cancer.
Material and methods: The study included 105 women (mean age 55±14 years) presenting HER2-positive early-stage invasive breast cancer. The treatment consisted in 6 cycles of adjuvant therapy including TZM, associated with docetaxel (n=100) or docetaxel and carboplatin (n=5). RNA was performed before the beginning of treatment (baseline), after in vivo red blood cell labeling by injection of stannous pyrophosphate, followed by injection of 740 MBq of 99mTc. Left Ventricular Ejection Fraction (LVEF) and Peak Ejection Rate (PER) were calculated for evaluation of LV systolic function; Peak Filling Rate (PFR) and Time to Peak Filling Rate (TPFR) were also calculated for evaluation of LV diastolic function. RNA was also performed to monitor LVEF during and after treatment. TZM mediated cardiotoxicity was defined according to the criteria established by clinical trials, specifically: a decline in LVEF of at least 15% below 50 %, or a decline in LVEF of at least 5% under 50%.
Results: Twenty patients (19%) developed a cardiotoxicity. No significant difference was observed concerning age, cardiovascular risk factors, fasting blood glucose level, heart rate, systolic blood pressure, initial LVEF and PER between patients with and without cardiotoxicity. However, with univariate analysis, baseline PFR lower than median value (Odds-Ratio [OR]: 3.2; 95% Confidence Interval [CI]: 1.2– 8.9; p=0.024) and baseline TPFR longer than 180 ms (OR: 6.0; 95%CI: 1.8 –19.9; p=0.003) were predictors. With multivariate analysis, only TPFR longer than 180 ms (normalized by age, heart rate and LVEF) (OR: 4.3; 95%CI: 1.1–16.7; p=0.034) remained an independent predictor of cardiotoxicity.
Conclusion: Evaluation of diastolic function could permit to select patients which needs optimal cardiac monitoring during adjuvant therapy of breast cancer by trastuzumab.