Trastuzumab-induced cardiotoxicity and its risk factors in real-world setting of breast cancer patients
Cardiotoxicity is the most important side effect of trastuzumab treatment. Heart function monitoring is recommended during the treatment which has led to growing use of resources. The aim of this retrospective study was to determine the frequency and timing of trastuzumab cardiotoxicity and its risk factors in real-world setting.
Single institute, retrospective collection of data on HER2+ breast cancer patients (n = 246) was carried out through a pharmacy search for patients who had received trastuzumab in 2006–2014. Clinical and pathological factors, treatment history, EF measurements, cardiac medications, cardiovascular disease history, cardiac symptoms, and survival data were collected from patient records.
32 patients (13%) had EF decline ≥ 10%, eleven (4.5%) had EF decline ≥ 20% within 1 year after trastuzumab initiation, and trastuzumab was discontinued due to suspected cardiotoxicity in six patients (2.4%). 49 patients (19.9%) experienced symptoms related to cardiotoxicity during therapy, which accumulated among those with EF drop. Underlying cardiovascular diseases and multiple (≥ 2) cardiac medications were related to EF drop (≥ 20%) and trastuzumab discontinuation. Majority of EF drops (≥ 10%) and trastuzumab discontinuations were seen within 6months of trastuzumab initiation and recovery of EF drop to < 10% of the baseline was seen in most cases (62.5%). There was no statistically significant difference in the survival of patients according to EF drop.
Trastuzumab cardiotoxicity seems to accumulate among patients with underlying cardiac conditions. EF monitoring could be targeted to risk groups without compromising of the cardiac health or survival of HER2-positive breast cancer patients.
KeywordsHER2 amplification Breast cancer Trastuzumab Cardiotoxicity
Compliance with ethical standards
Conflict of interest
Authors declare no conflict of interest. The study was funded by Oulu University Hospital, University of Oulu, and Finnish Cancer Society. According to national legislation, informed consent is not needed due to retrospective and non-interventional nature of the study. The opinions expressed in this article are the personal views of the author (OT) and may not be understood or quoted as being behalf or reflect the position of the Finnish Medicines Agency or European Medicines Agency.
- Bowles EJA, Wellman R, Feigelson HS, Onitilo AA, Freedman AN, Delate T et al (2012) Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst 104(17):1293–1305. https://doi.org/10.1093/jnci/djs317 CrossRefPubMedPubMedCentralGoogle Scholar
- ElZarrad MK, Mukhopadhyay P, Mohan N, Hao E, Dokmanovic M, Hirsch DS et al (2013) Trastuzumab alters the expression of genes essential for cardiac function and induces ultrastructural changes of cardiomyocytes in mice. PLOS One 8(11):e79543. https://doi.org/10.1371/journal.pone.0079543 CrossRefPubMedPubMedCentralGoogle Scholar
- FDA (2017) Trastuzumab prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/103792s5337lbl.pdf. Accessed 5 June 2018
- Goldhirsch A, Gelber RD, Piccart-Gebhart M, de Azambuja E, Procter M, Suter TM et al (2013) 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet 382(9897):1021–1028. https://doi.org/10.1016/S0140-6736(13)61094-6 CrossRefPubMedGoogle Scholar
- Guenancia C, Lefebvre A, Cardinale D, Yu AF, Ladoire S, Ghiringhelli F et al (2016) Obesity as a risk factor for anthracyclines and trastuzumab cardiotoxicity in breast cancer: a systematic review and meta-analysis. J Clin Oncol 34(26):3157–3165. https://doi.org/10.1200/JCO.2016.67.4846 CrossRefPubMedPubMedCentralGoogle Scholar
- Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A et al (2009) Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2–Positive, hormone Receptor–Positive metastatic breast cancer: Results from the randomized phase III TAnDEM study. 27(33):5529–5537. https://doi.org/10.1200/JCO.2008.20.6847
- Seferina SC, de Boer M, Derksen MW, van dB, van Kampen R,JW, van de Wouw A,J et al (2016) Cardiotoxicity and cardiac monitoring during adjuvant trastuzumab in daily dutch practice: a study of the southeast Netherlands breast cancer consortium. Oncologist 21(5):555–562. https://doi.org/10.1634/theoncologist.2015-0230 CrossRefPubMedPubMedCentralGoogle Scholar
- Telli ML, Hunt SA, Carlson RW, Guardino AE (2007) Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. 25(23):3525–3533. https://doi.org/10.1200/JCO.2007.11.0106
- von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE et al (2009) Trastuzumab beyond progression in human epidermal growth factor receptor 2–Positive advanced breast cancer: A german breast group 26/breast international group 03–05 study. 27(12):1999–2006. https://doi.org/10.1200/JCO.2008.19.6618