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. 2018 Aug 7;7(15):e008637.
doi: 10.1161/JAHA.118.008637.

Trastuzumab in Female Breast Cancer Patients With Reduced Left Ventricular Ejection Fraction

Somaira Nowsheen  1 , Khaled Aziz  1 , Jae Yoon Park  2 , Amir Lerman  2 , Hector R Villarraga  2 , Kathryn Jean Ruddy  3 , Joerg Herrmann  2
Affiliations

Trastuzumab in Female Breast Cancer Patients With Reduced Left Ventricular Ejection Fraction

Somaira Nowsheen et al. J Am Heart Assoc. .

Abstract

Background Trastuzumab is life-extending therapy for breast cancer patients overexpressing the human epidermal growth factor receptor 2 ( HER 2+), but has known cardiotoxic risk. We sought to determine if trastuzumab can be administered to patients with reduced baseline cardiac function at no higher cardiotoxicity risk than in those with normal cardiac function at baseline. Methods and Results We performed a retrospective study of women treated with trastuzumab for human epidermal growth factor receptor 2 breast cancer at Mayo Clinic Rochester between January 1, 2000 and August 31, 2015 with pre- and on-therapy echocardiograms available for review. A left ventricular ejection fraction (LVEF) <53% was considered abnormal, and a ≥10% decline in LVEF as evidence of cardiotoxicity based on the criteria of the American Society of Echocardiography. A total of 428 women were identified; 408 had a normal cardiac function ( LVEF 63.4±5%) and 20 had an impaired cardiac function ( LVEF 45.4±7%) before trastuzumab. Seven women (35%) with reduced LVEF at baseline had a ≥10% reduction in LVEF , compared with 179 (43.9%) of those with normal LVEF before trastuzumab initiation ( P= NS ). Symptomatic heart failure developed more often in patients with reduced versus normal baseline LVEF (25% versus 4.2%, P<0.05). After adjusting for patient age and breast cancer disease stage, survival rates over 5 years from time of diagnosis were found to be lower for patients with reduced baseline LVEF compared with patients with normal baseline LVEF ( P<0.001); the adjusted proportion of patients surviving at 5 years for those with low LVEF at baseline was 79% and for those with normal LVEF was 93%. Conclusions Women undergoing trastuzumab therapy for breast cancer with impaired baseline cardiac function experience no higher risk of LVEF decline, but more frequently develop symptomatic heart failure. While trastuzumab could be considered, these patients should be co-managed by a cardiologist.

Keywords: HER2; breast cancer; cardiomyopathy; cardiotoxicity; chemotherapy; heart failure; left ventricular ejection fraction; trastuzumab; treatment.

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Figures

Figure 1
Figure 1
Patient inclusion/exclusion flowchart. ECHO indicates Echocardiogram; HER2+, human epidermal growth factor receptor 2; HF, heart failure; LVEF, left ventricular ejection fraction.
Figure 2
Figure 2
Waterfall plot of maximum percentage point reduction in LVEF from baseline to any point in time during therapy with trastuzumab among patients with normal LVEF before trastuzumab (A) and patients with low LVEF before trastuzumab (B). LVEF indicates left ventricular ejection fraction.
Figure 3
Figure 3
Bar graphs illustrating the distribution of LVEF changes with trastuzumab therapy in patients diagnosed with HF (A) and patients without HF (B), stratified by baseline cardiac function (P=NS for panel A and P=0.0002 for panel B for group comparisons). LVEF indicates left ventricular ejection fraction.
Figure 4
Figure 4
Reversibility of trastuzumab‐induced decreases in LVEF, (A) related to the trastuzumab treatment regimen: no change in trastuzumab therapy (none), cessation of trastuzumab (held), or permanent stop of trastuzumab (stopped) with and without the addition of cardiovascular medication (added CV meds), and (B) by cardiovascular medications alone (P=0.03 for panel A and P=0.01 for (B) for group comparisons). CV indicates cardiovascular; LVEF, left ventricular ejection fraction.
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