Table 1: Incidence of trastuzumab-mediated Cardiotoxicity in Several Trials.
Study Number of Patients Type of Breast Cancer Number of weeks of Trastuzumab Used anthracyclines prior to Trastuzumab Definition of Cardiomyopathy Incidence of trastuzumab-mediated Cardiotoxicity
Vogel et al. (2002) [25] 114 HER2-positive metastatic breast cancer Median 16 weeks 2/3 patients developing TMC CHF symptoms, Cardiomyopathy, or a decrease in ejection fraction by 10% 2%
Guarneri et al. (2006) [26] 218 HER2-positive metastatic breast cancer Median 21.3 months 85% of TIC had prior anthracycline exposure LVEF decreasing below 50%, >20% drop in LVEF, or symptoms of CHF 28%
Suter et al. (2007) [27] 1,693 HER2–positive early invasive breast Caner 12 or 24 months 94% had adjuvant anthracycline based therapy LVEF decreasing below 50%, >10% drop in LVEF, or symptoms of CHF 4.3%
Perez et al. (2008) [28] 1,944 HER2–positive node-positive or high-risk node negative invasive breast cancer 52 weeks All arms treated with Doxorubicin + cyclophosphamide (AC) prior decreased >15% points from baseline, decreased below 50%, or symptoms of CHF Arm A: AC then Paclitaxel: 0.3%
Arm B: AC then Paclitaxel then trastuzumab: 2.8%,
Arm C: AC + Paclitaxel with trastuzumab: 3.3%
Gianni et al. (2010) [18] 117 HER2-positive locally advanced or inflammatory breast cancer 52 weeks neoadjuvant trastuzumab plus concurrent doxorubicin-including chemotherapy Development of EF <50% 2%
Untch et al. (2010) [29] 120 HER2-positive metastatic breast cancer 39-45 weeks trastuzumab plus concurrent epirubicin -including chemotherapy Decrease in LVEF of more than 10% to less than 50% Arm with trastuzumab + epirubicin 60 mg/m: 1.7%,
Arm with trastuzumab + epirubicin 90 mg/m: 5.0%
Slamon et al. (2011) [30] 3222 HER2-positive, node-negative or node-positive adenocarcinoma 52 weeks 1)doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T)
2) the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab)
3) or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH)		 Decrease in LVEF of more than 10% from baseline 1) AC-T 11.2
2) AC-T plus Trastuzumab 18.6
3) TCH 9.4
Romond, et al. (2012) [31] 944 Node Positive, HER2 Positive Breast Cancer 52 weeks Use of trastuzumab after 4 cycles of doxorubicin- containing chemotherapy decrease of LVEF >10% from baseline to a value less than 55% OR decrease of more than 5% to a value below 50% 4.0% (95% CI, 2.8% to 5.2%) vs 1.3% (95% CI, 0.5% to 2.1%) in control arm
Azambuja et al. (2014) [32] 1,673 In 1 year arm and 1,682 in two year arm HER2-positive Early Stage Breast cancer 52 or 102 weeks 94% of patients received an anthracycline-based chemotherapy prior decline of at least 10 percentage points from baseline LVEF and a decline to less than 50% 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year arm
Advani, et al. (2016) [33] 1876 Node positive or high-risk node negative breast cancer 52 Weeks Arm A: AC followed by weekly paclitaxel; Arm B: paclitaxel then 52 weeks of trastuzumab; Arm C: paclitaxel plus 52 weeks of trastuzumab followed by trastuzumab alone LVEF decreased by greater than 15% points or to 10% to 15% points below 50% Arm A: 0.6%
Arm B: 2.8%
Arm C: 3.4%
Yoon, et al. (2016) [34] 712 Breast cancer 52 weeks anthracycline-based treatment prior LVEF of <55% or the decrease in LVEF of >10% from the baseline LVEF 11.4%
Dang, et al. (2017) [35] 406 Node Negative, HER2 Positive Breast Cancer 52 weeks No anthracycline decrease of 10-15% in LVEF 3.2% (95% CI: 1.9-5.4%)
Cameron et al. (2017) [21] 5102 Node positive or high-risk node negative breast cancer 52 weeks or 104 weeks 94% received an anthracycline-based chemotherapy prior LVEF drop of at least 10 percentage points from baseline and to an absolute LVEF below 50% or cardiac death. 7.3% in the 2-years trastuzumab group, 4.4% in the 1-year trastuzumab group, and 0.9% in the observation group.