How Often Does Cardiotoxicity Lead to Discontinuation of Trastuzumab?

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Background: Trastuzumab (Herceptin) reduces the recurrence of HER2 positive breast cancer. Trastuzumab causes cardiotoxicity which is usually reversible. Nevertheless, once left ventricular ejection fraction (EF) decreases, trastuzumab is often discontinued, with the therapeutic advantage being lost or truncated. Objective: To determine how often cardiotoxicity leads to discontinuation of trastuzumab. Methods: We retrospectively reviewed the charts of 118 subsequent patients with advanced breast cancer (2003 to 2007) who received trastuzumab as an adjuvant treatment. EF was evaluated before treatment, then every 3 months by MUGA or Echo. Cardiotoxicity was defined as decrease of EF to<50%, or by ≥10% from the baseline, or symptoms of heart failure regardless of EF. Statistical analysis was done with Chi-square test and Fisher exact test. Results: All 118 women had EF>50% before treatment. The difference from the baseline was significant at all follow-ups (p<0.001), with no significant further decline after 3 months.

Table 1.

Cardiotoxicity developed in 39 women (33%). Trastuzumab was discontinued, permanently or temporarily, in 24 (20.3%). Lower EF at baseline had a strong association with a ≥10% drop of EF from baseline (p<0.001). Age and radiation did not influence cardiotoxicity.

Comorbidities, hypertension in particular, were associated with cardiotoxicity (p<0.05). In patients with comorbidities (n=40), those treated with ACE inhibitors, beta-blockers, and/or statins appeared to have less overall cardiotoxicity (36% vs. 60%), decrease of EF to<50% (12% vs. 33.3%), and trastuzumab discontinuation (20% vs. 40%) than those treated with other drugs. Conclusions: Highly prevalent cardiotoxicity (33%) led to discontinuation of trastuzumab in 20% of women with advanced breast cancer. Lower baseline EF and comorbidities, especially hypertension were the most significant predictors of cardiotoxicity. Further studies on possible prevention in high risk women are warranted.