Abstract P1-15-01: Adjuvant trastuzumab +/- anthracycline and cardiotoxicity in a community cohort of 962 HER2+ breast cancers from 2005-2011: Comparison of incidence by risk factors and by diagnostic codes vs clinical chart review
Authors: Fehrenbacher L , Capra A , Krishnaswami A , Quesenberry C , Habel L 
Published: May 2016

Background: Prospective clinical trials using clinical criteria and observational studies using diagnostic codes from electronic health records have reported seemingly contradictory cardiotoxicity risk for adjuvant trastuzumab (T). Accurate estimates of individualized patient specific cardiotoxicity risk are essential for treatment decisions in early HER2+ breast cancer (BC).

Methods: 1,109 consecutive non-metastatic HER2+ invasive BC's diagnosed 5/1/2005 to 12/31/2011 at Kaiser Permanente Northern California receiving adjuvant T were reviewed for symptomatic congestive heart failure (SxCHF), baseline and post-T cardiac ejection fraction (EF), anthracycline (A) use, and CHF risk factors (RF) including age, race, hypertension (HTN), diabetes (DM), obesity, smoking. Records of patients with CHF ICD9 codes or an EF drop to &lt;50% were reviewed by a RN, a cardiologist, and an oncologist. Primary outcomes were SxCHF (NYHA Class II or higher), EF fall to &lt;50%, and &lt; 38 weeks of T (75% of prescribed).

Results: Median age of 962 eligible patients was 54 years (range 24-95). 305 (31.7%) were &gt; 60 years old. During a median follow-up of 4.1 years, 4.6% of patients had CHF ICD9 codes, but only 2.5% had SxCHF or cardiac death confirmed by clinical review. At 1 year, cumulative incidence of an EF fall to &lt;50% was 5.7% with T alone and 17.7% with T+ A. A total of 15.3% finished &lt;38 weeks of T, 9.4% with T alone and 20.6% with T+A. The overall 2- and 5-year cumulative incidence of SxCHF/cardiac death was low: 1.3% and 2.7% with T alone and 2.2% and 3.1% with T + A. These rates were lower than reports based solely on diagnostic or billing codes, and varied substantially by RF (see table). The rates were similar to those predicted by the NSABP B-31 Cardiac Risk Score. Clinical heart failure based on diagnostic codes was not confirmed at chart review 48% of the time. Results from multivariable analyses will be presented.

Predictors of Trastuzumab Cardiotoxicity  Cumulative Incidence (%)PredictorsNFall EF to&lt;50%Symptomatic CHF  1-year2-year5-yearAll96212.01.82.8Anthracycline50517.72.23.1Non-anthracycline4575.71.32.7Age&lt;6065711.71.11.1Age 60-6922212.61.43.8Age 70-797112.77.111.0Baseline EF 50-55%9230.78.88.8HTN dx39212.63.44.7BMI 30+31516.32.64.5DM Dx10315.55.06.9Smoking (ever)33314.23.76.1HTN and BMI 30+18215.53.96.0HTN, BMI 30+, DM5016.08.212.2Age&lt;50, BMI&lt;30, No HTN/DM2197.30.00.0Age&gt;60, 2+ RF(HTN, DM, BMI 30+)10114.95.08.9

Conclusions: Risk of clinically confirmed CHF/cardiac death was substantially lower than risk based on ICD codes alone. Risk was consistent with prior clinical trials and differed substantially by age, baseline EF, use of A, and other CHF risk factors. Greatest risk was with age of 70+, borderline baseline EF, and comorbidities known to increase CHF risk. Quite low risk (1.1% at 5 years) was seen in patients under 60 years old.

Citation Format: Fehrenbacher L, Capra A, Krishnaswami A, Quesenberry C, Habel L. Adjuvant trastuzumab +/- anthracycline and cardiotoxicity in a community cohort of 962 HER2+ breast cancers from 2005-2011: Comparison of incidence by risk factors and by diagnostic codes vs clinical chart review. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-15-01.