Abstract P5-18-14: Cardiac monitoring during adjuvant trastuzumab therapy for breast cancer
Authors: Ng D , Ferrusi I , Khong H , Earle C , Trudeau M , Marshall D , Leighl N 
Published: August 2014

Abstract
Background: Adjuvant trastuzumab improves survival in HER2+ breast cancer. Cardiac toxicity is an important potential side effect. We report real world practice patterns in cardiac monitoring and outcomes during adjuvant trastuzumab therapy in Ontario.
Methods: A cohort of female patients diagnosed with early breast cancer from Jan 1, 2006 to Dec 31, 2007 and who received trastuzumab was identified retrospectively through linkage of provincial administrative and registry databases. Demographic, pathology, treatment, hospital admissions, claims for cardiac tests (MUGA or echo), and outcomes were extracted for individuals. Pre-existing cardiac disease (CHF, MI, angina, valve disorder, arrhythmia, cardiomyopathy) and risk factors (diabetes, lipid disorder, hypertension) were classified using ICD-10 codes. Appropriate cardiac monitoring definitions were based on published trials and expert opinion. Symptomatic cardiac toxicity was defined as a physician claim or hospital admission with a cardiac diagnosis occurring within 2 years of the first trastuzumab dose. Asymptomatic cardiac toxicity was defined as temporary or permanent cessation of trastuzumab with additional cardiac tests. Patients were categorized into treatment groups: G1 received at least 17 doses (standard 3-weekly administration for 51 weeks) with no complications; G2 stopped early for non-cardiac reasons (no additional cardiac tests); G3 had symptomatic or asymptomatic cardiac toxicity. Analyses of patient, treatment and system factors possibly affecting cardiac monitoring and toxicity were performed.
Results: 1,357 patients diagnosed with early breast cancer between 2006–7 received trastuzumab (median = 18 doses). 77% received anthracyclines; 4.1% had at least 1 cardiac risk factor. The majority (91%) had a baseline cardiac test, including 96% of those with cardiac risks. Geographic region was associated with baseline testing, but multivariable analysis of other factors including urbanicity, left lateral radiation, age, income, and anthracycline use, did not explain the variation in baseline testing patterns. The majority, 81%, had ≥3 cardiac tests, 62.2% had ≥4. Cardiac monitoring was deemed appropriate in 80.7% of patients without cardiac events, and 73.4% in those with symptomatic or asymptomatic cardiac events. Multivariable analysis revealed duration of trastuzumab to be the most significant factor associated with appropriateness of cardiac monitoring (G1 - OR 0.62, p = 0.018, 95% CI 0.45–0.92; G3 - OR 4.56, p &lt; 0.001, 95% CI 2.47–8.42). 297 patients (22%) experienced symptomatic (7%) or asymptomatic (15%) cardiac toxicity. Duration of trastuzumab (&lt;17 doses; OR 6.47, p &lt; 0.001, 95% CI 4.79–8.75) was associated with cardiac toxicity.
Conclusions: The majority of early breast cancer patients that received adjuvant trastuzumab in Ontario between 2006–7 had cardiac monitoring consistent with clinical trials. Cardiac toxicity in this real world population, as defined by our database analysis, was unexpectedly higher than reported in trials. Shorter duration of trastuzumab was associated with cardiac toxicity, likely reflecting the practice of stopping trastuzumab in the presence of cardiac events.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-14.