Trastuzumab, a humanized monoclonal antibody significantly improves outcomes in Her2 neu positive breast cancer. The incidence of cardiotoxicity with trastuzumab is approximately 8-10%. The present study was designed to analyze the incidence and risk factors associated with trastuzmab related cardiotoxicity.
The present study was a single institutional retrospective analysis of the incidence of trastuzumab induced cardiotoxicity in nonmetastatic invasive breast cancer from January 2011 to December 2018. Trastuzumab induced cardiotoxicity (TIC) was defined as symptomatic heart failure or asymptomatic decline in left ventricular ejection fraction (LVEF) by > 10% or LVEF < 50%. Risk factors analysed were BMI (≥30 vs < 30), history of diabetes, hypertension, coronary artery disease (CAD) (yes or no), left sided radiotherapy (RT) and prior anthracycline (yes or no).
Data of 246 patients with Her2 neu positive breast cancer was collected. Of these, 117(47.5%) received trastuzumab. The median age at presentation was 51 years (range,28-72). Of 117 patients who received adjuvant trastuzumab TIC was seen in 16(13.6%) patients, asymptomatic LV dysfunction in 9.4% and symptomatic LV dysfunction in 4.2% patients. The median baseline ejection fraction of 65% (range, 56 - 72). The median time to development of TIC was 18.5 (range, 3-52) weeks and median trastuzumab cycle for TIC was 6 (range, 2-16). Presence of ≥ 2 risk factors (20%) had significant impact on incidence of TIC compared to < 2 risk factors (p = 0.04). 10 (62.5%) patients were rechallenged with trastuzumab and 6(37.5%) discontinued trastuzumab. Following rechallenge 1 patient developed asymptomatic decline in EF and 1 developed symptomatic heart failure and were stopped completely. No cardiacrelated mortality was seen.
Risk factors in relation to TICRisk factor TIC Present TIC absent p Value BMI ≥ 30 < 30 2 14 14 78 0.54 History of diabetes Yes No 3 13 21 80 0.88 History of hypertension Yes No 8 8 31 70 0.2 CAD Yes No 1 15 2 99 0.8 Left side RT Yes No 9 7 23 78 0.012 Prior anthracycline Yes No 13 3 65 36 0.29
Approximately 14% developed TIC which was higher in real-world population compared to that seen in clinical trials. Left sided RT to chest and presence of 2 or more risk factors had significant impact on development of TIC. Stringent monitoring of cardiac function to avoid cardiotoxicity and prompt resumption of trastuzumab following recovery may further improve outcomes in nonmetastatic breast cancer.
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Department of Medical Oncology, NIMS, Punjagutta, Hyderabad, India.
Has not received any funding.
All authors have declared no conflicts of interest.