Abstract P5-14-18: Cardioprotective therapy in breast cancer patients with subclinical and clinical cardiotoxicty
Authors: Dent Susan Faye , Steen Henning , Montenbruck Moritz , Esch Sebastian , Wulfing Pia , Janson Kyle , Lenihan Daniel 
Published: March 2020

Abstract
Background: Modern breast cancer (BC) therapies have led to significant improvement in disease free and overall survival, but are associated with off target toxicity including cardiotoxicity. Current cardio-protective strategies have included all patients (pts) receiving potential cardiotoxic cancer therapy with modest clinic benefit. In this pilot study, we examined the role of cardioprotective therapy (CPT) in BC pts identified as having subclinical or clinical cardiotoxicity.
Methods: Early BC patients (pts) in the PREFECT Study (NCT03543228) were serially examined for cardiac function up to 1-year after initiation of chemotherapy (CT) using cardiac magnetic resonance (CMR) imaging. CT included epirubucin and cyclophosphamide every 2 weeks x 4 followed by paclitaxel (weekly x 12 or every 2 weeks x 4) and targeted therapy (e.g trastuzumab) if human epidermal growth factor receptor 2 (HER2) positive. Myocardial strain was quantified using fast-strain encoded (fast-SENC) across 37 left and 11 right ventricular segments. The percent of segments with normal strain (≤17%) was calculated (% normal MyoStrain). Clinical cardiotoxicity (CTx) was defined as an absolute change in left ventricular ejection fraction (LVEF) &gt; 10 % to below 53 %; subclinical CTx was defined as an asymptomatic decrease in LVEF of 15 % or worsening global longitudinal strain (GLS) &gt; 15 %, or abnormal cardiac biomarkers (troponin, brain natriuretic peptide (BNP), N terminal-BNP). Descriptive statistics were used to summarize subject demographics, medical history, cardiovascular measures, and response to CPT. Response to CPT was defined as restoration of cardiac function, wall motion, absence of cardiac symptoms, and normalization of cardiac biomarkers.
Results: A total of 40 BC pts age 50 (+/- 12.5) years and body mass index of 25.4 (+/- 5.8 kg/m2) were enrolled and followed for 273 +/- 126 days. Clinical CTx was observed in 4 (10 %) patients and subclinical CTx in 15 (37.5%). Pts with clinical CTx were older, had a higher Charlson co-morbidity index, and had significantly reduced cardiac function (49.5% +/- 9.5% normal MyoStrain) despite normal CMR LVEF (54.2% +/- 4.0%). Pts with subclinical CTx had a smaller decline in cardiac function (58.6% +/- 9.1% normal MyoStrain) despite normal CMR LVEF (56.4% +/- 4.9%). 12/19 pts with CTx showed improvement with CPT (candesartan -9, ramipril -2, lisinopril -1, and beta-blockers (BB): yes -8, no -4); 1 did not improve, 4 did not receive CPT and 2 remained on ineffective anti-hypertensive medication. Pts at baseline, without CTx, or showing improvement based on CPT, had significantly higher % normal MyoStrain (79.0% +/- 11.8%, 79.5% +/- 9.3%, and 80.4% +/- 9.8% respectively) and normal CMR LVEF (59.7% +/- 4.2%, 59.9% +/- 4.9%, and 60.7% +/- 5.1% respectively).
Discussion: Identifying BC pts at high risk of experiencing cancer therapy related cardiotoxicity enables a more tailored approach to cardio-preventative strategies. In this pilot study the majority (12/19) of BC pts identified with subclinical or clinical CTx demonstrated improvement in cardiac function with CPT. Proactive tailored cardio-protection may also prevent long term permanent cardiac dysfunction and associated heart failure. Larger, multi-center trials are warranted to evaluate the short and long term benefits of CPT in this pt population.
Citation Format: Susan Faye Dent, Henning Steen, Moritz Montenbruck, Sebastian Esch, Pia Wulfing, Kyle Janson, Daniel Lenihan. Cardioprotective therapy in breast cancer patients with subclinical and clinical cardiotoxicty [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-18.