Assessment and monitoring of cardiotoxicity in Breast Cancer patients treated with  HER2-directed Agents (Trastuzumab, Pertuzumab, and Ado-trastuzumab emtansine (T-DM1)


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Sudha Karanam1,Mariam Jafri1,Daniel Rea1,Nyein Su Tun1
1University Hospital Birmingham NHS Trust

Abstract

Background

Over recent years, use of anti-HER2 agents like Trastuzumab, Pertuzumab , Trastuzumab-emtansine (TDM1; Kadcyla) in early breast cancer (EBC) and Metastatic Breast Cancer( MBC) has increased due to improvement in survival. These agents are associated with cardiotoxicity, but there is limited data on cardiotoxicity with Trastuzumab-emtansine and Pertuzumab.

Method

We retrospectively identified women with HER2 positive breast cancer who received Trastuzumab, Pertuzumab, or Trastuzumab-emtansine between January 2015 and June 2018. Patients included if their baseline Left ventricular ejection fraction (LVEF)≥ 55%. Cardiotoxicity was assessed by serial LVEF monitoring with echocardiography at baseline and every three months during and after anti-HER2 therapy. Chi-square tests were used to identify association between risk factors and cardiac events.

Results

100 patients were included, with a mean age 56.8 years (32-85years) and an average BMI  29.11 ± 6.08 kg/m2, (range 17.6- 44.6 kg/m2). Among the whole cohort, 27% had hypertension, 10% had diabetes. 24 patients had a decline in LVEF of >10% from the baseline (15 from Trastuzumab+Pertuzumab treatment arm, 9 from Trastuzumab-emtansine); 2 patients showed asymptomatic decline of LVEF<50% (both cases from Trastuzumab+Pertuzumab treatment), no patients experienced symptomatic heart failure. Cardiotoxicity occurred within first six months of the therapy and was reversible with standard medications and cessation of anti-HER2 therapy was not required in any patient. No specific cardiovascular risk factor was identified for anti-HER2 associated cardiotoxicity.

Conclusion

LVEF reduction occurred in 24% of patients. However, symptomatic heart failure and cessation of treatment was not required.  Cardiotoxicity was reversible with standard treatment. Continued prospective evaluation of cardiotoxicity is recommended given increasing use of these agents in early breast cancer.