Factors Affecting Long-Term Safety of Trastuzumab in Patients with Early HER2-Positive Breast Cancer
|Boekhout AH1*, Werkhoven ED2, Liebergen R3, Korse CM4, Burylo A5, Trip AK6, Beijnen JH7,8 and Schellens JH1,8|
|1Division of Clinical Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands|
|2Biometrics Department, Netherlands Cancer Institute, Amsterdam, The Netherlands|
|3Department of Cardiology, Slotervaart Hospital, Amsterdam, The Netherlands|
|4Department of Clinical chemistry, Netherlands Cancer Institute, Amsterdam, The Netherlands|
|5Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands|
|6Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands|
|7Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands|
|8Department of Pharmaceutical Sciences, Science Faculty Utrecht University, Utrecht, The Netherlands|
|*Corresponding Author :||Boekhout AH
Division of Clinical Pharmacology
Netherlands Cancer Institute. Plesmanlaan 121
1066 CX, Amsterdam, The Netherlands
E-mail: [email protected]
|Received July 25, 2014; Accepted September 24, 2014; Published September 26, 2014|
|Citation: Boekhout AH, Werkhoven ED, Liebergen R, Korse CM, Burylo A, et al. (2014) Factors Affecting Long-Term Safety of Trastuzumab in Patients with Early HER2-Positive Breast Cancer. Adv Pharmacoepidemiol Drug Saf 3:160. doi:10.4172/2167-1052.1000160|
|Copyright: © 2014 Boekhout AH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
Background: Trastuzumab treatment is associated with cardiac dysfunction. We evaluated the incidence of cardiotoxicity during and long-term after trastuzumab treatment in an unselected early breast cancer population.
Methods: This study included a retrospective part, the chemotherapy- and trastuzumab treatment period and a prospective part, the period of data collection long-term after trastuzumab treatment. Cardiac evaluation included left ventricular ejection fraction (LVEF) changes and an evaluation of symptomatic cardiotoxicity. Cardiac events were defined as a decrease of 10 percentage points in LVEF compared with baseline and to an absolute LVEF of below 50%. Secondary outcomes included the evaluation of cardiac markers (B-type natriuretic peptide and troponins) and single nucleotide polymorphisms (SNPs) in the HER2 gene as parameters to detect or predict trastuzumab-related cardiotoxicity.
Results: Overall, 105 patients were evaluable for the primary endpoint. The 3-year cumulative incidence of cardiac events was 12% (95 CI, 4%-19%). All 8 patients with a cardiac event were pre-treated with anthracyclines and cyclophosphamide and 7 of them recovered partially or completely. Four patients experienced symptomatic cardiotoxicity, of who 2 recovered completely and the other 2 recovered partially. No statistically significant association was observed between cardiac events and cardiac markers or SNPs.
Conclusion: Trastuzumab treatment in combination with anthracy
cline-based chemotherapy is associated with significant and only partly reversible cardiac dysfunction. Baseline LVEF value is a prominent predictor for long-term LVEF especially, in patients who are not treated with anthracycline-based chemotherapy. These findings can be used to establish optimal monitoring strategies in trastuzumab treatment.