Abstract CT321: Prevention of cardiac dysfunction during adjuvant breast cancer therapy: the PRADA study
Authors: Gulati Geeta , Heck Siri Lagethon , Ree Anne Hansen , Bratland Åse , Steine Kjetil , Schulz-Menger Jeanette , Gravdehaug Berit , Hoffmann Pavel , Røsjø Helge , Geisler Jürgen , Omland Torbjørn 
Published: May 2015

Purpose: Breast cancer is the most common malignancy in women worldwide. Treatment modalities include chemotherapeutic regimens containing anthracyclines, radiotherapy, and if HER-2 positive, the monoclonal antibody trastuzumab. Anthracyclines and trastuzumab are known to cause cardiac dysfunction, which may interrupt the anticancer treatment and thus increase the risk of cancer relapse. In previous observational trials, of patients with established left ventricular dysfunction following high-dose chemotherapy, treatment with angiotensin converting enzyme inhibitors and beta-blockers appeared to be associated with beneficial effects.

Experimental design: A randomized, placebo-controlled, 2x2-factorial, double-blinded study is currently conducted at Akershus University Hospital, Lørenskog, Norway. In total, 120 women receiving adjuvant breast cancer therapy including anthracyclines and, if indicated, trastuzumab and/or radiation will be enrolled. Inclusion criteria comprise age between 18-70 years, Eastern Cooperative Oncology Group performance status ≤1, serum creatinine &lt;140umol/L or estimated creatinine clearance &gt;60 ml/min, systolic blood pressure ≥110 and ≤170 mmHg and left ventricular ejection fraction ≥ 50%. Cardiac magnetic resonance imaging (cMRI) with gadolinium contrast, echocardiography, cardiovascular biomarkers, and electrocardiogram are used to monitor cardiac function and injury.

Objective: To assess the prophylactic effect of candesartan and metoprolol monotherapy, or their combination on global left ventricular systolic function, as assessed by cMRI of the heart, during postoperative, adjuvant chemotherapy with or without anti-HER-2 treatment and/or radiotherapy for early breast cancer. Secondary objectives include assessment of cardiac function and injury by echocardiography and cardiovascular biomarkers.

Status: At our institution, postoperative, adjuvant chemotherapy was considered for 261 women in the period of September 2011 through November 2013. Among these, 105 (40%) were randomized for the PRADA-study. So far, 27 of 105 (26%) women included have received trastuzumab. The inclusion is estimated to continue through March 2014.

Study value: The PRADA study addresses an important clinical problem in the early breast cancer population. The study will provide novel and clinically important data concerning the potential prevention of cardiac dysfunction during adjuvant breast cancer treatment. Our first experience with repeated cardial cMRIs and echocardiography during adjuvant therapy in early breast cancer patients on cardioprotective therapy will be presented and discussed.

Citation Format: Geeta Gulati, Siri Lagethon Heck, Anne Hansen Ree, Åse Bratland, Kjetil Steine, Jeanette Schulz-Menger, Berit Gravdehaug, Pavel Hoffmann, Helge Røsjø, Jürgen Geisler, Torbjørn Omland. Prevention of cardiac dysfunction during adjuvant breast cancer therapy: the PRADA study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT321. doi:10.1158/1538-7445.AM2014-CT321