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

Abstract

BackgroundTrastuzumab is life‐extending therapy for breast cancer patients overexpressing the human epidermal growth factor receptor 2 (HER2+), 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 ResultsWe 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%.ConclusionsWomen 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.

Detailed phenotyping reveals distinct trajectories of cardiovascular function and symptoms with exposure to modern breast cancer therapy

“…26 In addition, a study of patients with breast cancer who were treated with trastuzumab therapy found that a decline in LVEF ≥10% was more frequent in those with normal LVEF at baseline (defined as ≥53%) compared with those with a low baseline LVEF. 27 There was a trend toward a higher likelihood of class 3 membership with older age, black race, and hypertension, and a lower likelihood in those individuals with a history of cardioprotective medication use at baseline. We postulate that we were limited by statistical power in our ability to adequately assess the associations between baseline cardiovascular risk factors and medications and LVEF trajectory class membership.…”

“…Another study demonstrated that the mean baseline LVEF was higher in patients with non‐Hodgkin lymphoma who developed an LVEF decline >10% to ≤50% after exposure to doxorubicin compared with those who did not develop cardiotoxicity . In addition, a study of patients with breast cancer who were treated with trastuzumab therapy found that a decline in LVEF ≥10% was more frequent in those with normal LVEF at baseline (defined as ≥53%) compared with those with a low baseline LVEF …”

Cardiotoxicidade nas Terapias Neoadjuvante e Adjuvante do Câncer de Mama

“…Esse resultado foi superior ao estudo de Dores et al 18 , que constataram que 3,3% das pacientes tiveram FEVE abaixo de 55%. Nowsheen et al 19 demonstraram que 73,2% das pacientes que tinham FEVE basal normal e que foram submetidas ao tratamento com trastuzumabe após uso de antraciclinas tiveram uma redução da FEVE em mais de 10%, caracterizando o efeito cumulativo e potencializador desses medicamentos quanto à cardiotoxicidade.…”

Clinical Impact of Interruption in Adjuvant Trastuzumab Therapy in Patients with Operable HER-2 Positive Breast Cancer

“…Patients receiving adjuvant trastuzumab undergo periodic monitoring of LVEF every three months while on therapy (14); those experiencing decline in LVEF ≥ 16% from baseline or LVEF below normal limits and ≥ 10% decline are asked to withhold treatment for at least four weeks and continue LVEF monitoring every four weeks until resolution. Older age (> 50 years) and pre-existing cardiovascular (CV) diseases, such as uncontrolled hypertension and congestive heart failure, have been implicated in increasing the risk of TIC (10,(15)(16)(17)(18)(19).…”