Abstract ED01-03: Integrative prevention

Abstract

Abstract Progress in cancer prevention is linked to improved methods of cancer risk assessment, and to the identification and development of effective interventions to reduce cancer risks. But the ultimate goal of prevention is not just in reducing the risk of a single cancer, but in reducing the risks of several cancers, reducing the risk of chronic disease outcomes more broadly, or promoting sustained health - so called, integrative prevention. However, achieving the goals of integrative prevention through lifestyle modifications and/or chemopreventive agents with acceptable levels of safety has been challenging.1 Several chemopreventive agents have now been clearly demonstrated in experimental studies as efficacious in reducing cancer risks within a single organ, but few of these are in routine clinical use due to an unacceptable or unconvincing level of evidence that benefits of administration outweigh the potential harms. For example, tamoxifen is very effective in reducing the risk of invasive and noninvasive breast cancer in women at moderate risk,2 but concerns about venous thrombosis and uterine cancer have tempered enthusiasm for the agent's routine application in this setting. Aspirin and celecoxib can be given to reduce the incidence or recurrence of colorectal adenomas in various cohorts at moderate risk of colorectal cancer,3–5 but the untoward risks of upper gastrointestinal ulceration or serious cardiovascular events has thwarted adoption as a reasonable strategy in all but those with extreme cancer risks. In addition, some interventions have been suggested for preventive recommendations based largely on observational data. For example, American Cancer Society guidelines to increase the consumption of fruits, vegetables, and whole grains and to limit alcohol are largely premised on epidemiologic data suggesting the benefits of such a diet.6 Folic acid fortification of flour and related grain products in the U.S. was mandated by the FDA in 1996 based upon a variety of research including experimental studies that demonstrated reductions in neural tube defects following administration, and the presumptive safety of folic acid supplementation. But more recently, some studies and investigators have raised questions about the safety of such an approach based on concerns of increased risks for neoplasia.7 Supplementation of calcium in the American diet is another area in which there are data suggesting possible health benefits as well as harms. Finally, achieving and maintaining a “healthy” body mass index is another topic of importance and controversy, not so much due to an inconsistency in data across study designs, but to the fundamental questions of identifying an optimal level and timing. Most interestingly, the examples cited above raise the important question of what level of evidence for benefits relative to risks is necessary to allow health systems, agencies, or practitioners to be able to make preventive recommendations with a reasonable level of confidence. This is a particularly important and timely issue because of the significant costs, challenges in feasibility, and limitations involved with trials testing even the most promising interventions for specific cancer preventive indications. Among the most significant limitations, one must always consider carefully the limited power of most trials to detect less common or delayed risks, as well as their inability to assess the generalizability of benefits and risks in typically homogeneous trial populations. Therefore, although the notion of integrative prevention is wholly appealing, progress toward this goal has been slow and difficult, and is likely to remain so. It is important to consider the conceptual foundations of integrative prevention, and the inferential evidence base typically required for action. As the field progresses, we'll need to address the barriers inherent in research of this nature, develop possible solutions to them, and consider how those on the front-lines of clinical preventive care and public health practice can best weigh the evidence to make well-informed decisions. Citation Information: Cancer Prev Res 2010;3(1 Suppl):ED01-03.