The use of cardiovascular disease states as exclusion criteria in breast cancer trials: A 4-decade perspective.

Abstract

e18053 Background: At the time of diagnosis, patients with breast cancer have a higher prevalence of cardiovascular risk factors than the general population. It is likely that the prevalence of actual cardiac disease is also increased, although no published data is available to support this claim. Individuals with breast cancer who also have heart disease are typically disqualified from clinical trials. We attempted to define the evolution of cardiovascular exclusion criteria in clinical trials of breast cancer over the decades. Methods: We searched the NEJM for original research in “breast cancer” published from 01/1980 to 12/2016. We reviewed the nature of cardiovascular disease as exclusion parameters as well as trends over time. Results: 20 RCTs were analysed, 5 from each decade (total # of patients 21,231). Mean number of cardiac exclusion criteria per study increased over the decades (1980s: 0; 1990s: 0.2; 2000s: 1; 2010s: 7). The most common cardiac exclusion criteria were CHF and recent MI (35% and 25% of studies, respectively). Factors associated with a higher likelihood of having a cardiac exclusion criteria were source of funding (industry vs. university: 77.7% vs. 18.1%, P-value 0.005) and study’s country of origin (U.S versus non-U.S: 57.1% versus 16.6%, P-value 0.02). Prior to 2010, the complete list of exclusion criteria was available with the manuscript. From 2010, it became embedded within the study’s protocol file (and not printed). Cardiovascular AEs were infrequent (1980s: 0.02%; 1990s: 0%, 2000s: 0.08%; 2010: 0.29%). Before 2000, studies described the significant cardiac toxicity in the manuscript. After 2000, a comprehensive registry of AEs contained within supplementary files became the norm. Conclusions: The use of cardiovascular exclusion criteria in clinical trials in breast cancer has become common over the past decades. Currently, it is almost impossible for a woman to enter a trial with even a single cardiac condition. Given that a sizeable fraction of breast cancer patients has cardiac disease, consideration should be given to narrowing the scope of cardiac exclusion criteria to allow more patients to participate, while making the results of those trials more broadly generalisable.