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EDITORIAL |
Dr. Chlebowski is Professor of Medicine, Division of Medical Oncology, Harbor-UCLA Research and Education Institute, Torrance, CA.
The revised American Cancer Society (ACS) guidelines for nutrition and physical activity for cancer survivors published in this issue of CA is a careful, objective analysis that used prospectively identified criteria to address an important area in clinical oncology. Thse guidelines represent a virtual clearinghouse of information on nutrition and physical activity for health care providers and for survivors of cancer and their families. The ACS and specifically the scientists and individuals involved in this considerable effort should be congratulated.
If we step back and review the recommendations, what bigger picture comes into focus? The four cancers specifically targeted for attention, including breast, colorectal, prostate, and lung, represent the most common cancers in the United States and account for approximately one half of all nonskin cancers annually.1 As we examine the conclusions by grade across cancer types for cancer recurrence, no interventions are thought to warrant convincing evidence for benefit in cancer survivors. In fact, only "striving for healthy weight after treatment" is graded to have a probable benefit on cancer recurrence in one disease (breast cancer). In general, the graded conclusions considerably overlap the cancer categories, and many of the favorable scores for overall survival depend on the anticipated effect on heart disease. Finally, some of the recommended strategies, such as weight loss, include a phrase that such interventions are appropriate "as long as it is approved by the treating oncologist." One perspective on the biologic and historical factors influencing the development of the information reviewed by this ACS guidelines panel is outlined below.
Examination of the purported mediating mechanisms for the nutrition and physical activity interventions facilitates understanding of the overlap in recommendations across not only types of cancer but also heart disease. To begin with the cancers, with the exception of lung cancer (importantly under the influence of smoking), breast, colorectal, and prostate cancers are all thought to be modulated in important ways by hormonal systems involved in cell growth and differentiation. These include reproductive hormones (androgens and estrogens) and insulin-regulatory hormones. As one example, obesity is associated with increased levels of estradiol, estrone, testosterone, androstenedione, insulin, and insulin-like growth factor type 1. In addition, these hormone systems have been linked to other life-threatening diseases, with higher fasting insulin associated with not only colon and breast cancer but also diabetes, heart disease, stroke, and cognitive dysfunction.2 Thus, the anticipated or observed effect of nutrition and physical activity change on chronic disease is based on sound biologic observations.
For the pharmacologically oriented discipline of clinical oncology, a reasonable question could be posed. If estrogen and insulin are the perceived problems influencing cancer growth, why not attack the problem directly using interventions such as the aromatase inhibitors to decrease estrogen and metformin levels to counteract insulin action? The answer is that such pharmacologic interventions are receiving considerable attention, but the results of such activities cannot be interpreted as direct tests of diet-cancer or physical activity-cancer relations. Such interventions target just one parameter and cannot fully reflect the body’s response to changes in whole foods or physical activity.3
A recent example of the problems of basing a pharmacologic therapy on biologic inference comes from the women’s health area. For more than half a century, the medical community has considered prescription of estrogen plus progestin to postmenopausal women to constitute hormone replacement therapy. Clinical benefit was antici-pated based on presumed maintenance of a hormone-rich, low-chronic-disease risk premenopausal hormonal environment. However, when evaluated in a randomized trial, the recent reports of the Women’s Health Initiative4–6 indicated that conjugated equine estrogens and medroxyprogesterone acetate do not represent hormone replacement therapy but rather a pharmacologic intervention associated with a broad range of increased chronic disease risk. The areas of nutrition and physical activity represent separate disciplines to be judged on their own merits in terms of their effect on chronic disease risk.
Is it fair for the guidelines panel to consider survival value based on the effect of nutrition or physical activity interventions on diseases other than cancer in a cancer survivor population? The answer certainly is yes. Increased and more effective screening procedures for prostate, breast, colorectal, and lung cancer are identifying cancer at increasingly earlier stages. For example, a 50-year-old woman with a mammographically detected invasive breast cancer measuring less than 1 cm with a 10% 10-year recurrence risk certainly might benefit from a reduction in heart disease risk associated with adopting a program of increased physical activity and weight reduction.
One additional factor in favor of nutrition, weight loss, and physical activity intervention strategies relates to safety. The strategies in this area with most current support could be considered a reaction to Western lifestyles and revolve around reducing body weight, increasing physical activity, and adopting a diet lower in calories and fat and higher in fruit and vegetable intake. These changes have been characterized as a return to the "evolutionary norm."7 As such, they are likely to be safe interventions because they reflect conditions under which hormonal control systems likely developed.
The guidelines panel could find no nutritional intervention for which convincing evidence for cancer recurrence risk reduction is available. Convincing evidence in this context usually requires a randomized clinical trial outcome difference. Why are such results lacking in the nutrition and physical activity areas? One reason is that this research area has received less focused attention and is likely perceived by oncologists and even funding agencies as a minor area of therapeutic investigation. In this regard, I turned to the Annual Proceedings of the American Society of Clinical Oncology, the largest forum for reporting clinical cancer-related investigations, for proportional content related to the area of nutrition and diet. In the past 5 years (through 2003), of 15,015 abstracts, only 25 were identified in the diet-nutrition area. Eight represented classic nutritional support (interventions to maintain weight in end-stage cancer patients), 5 related to complementary and alternative medicine, and only 12 (less than one tenth of 1%) were reports relevant to evaluating the interventions outlined in the ACS guidelines.
The ACS guidelines for nutrition and physical activity for cancer survivors assemble a powerful and persuasive argument that both increased physical activity and weight loss have sufficient scientific support to justify full-scale randomized clinical trials in specific cancer survivor populations. This report should provide an impetus for clinical investigators and funding agencies to give careful consideration to support of such efforts. We can be optimistic that future cancer survivors will be the beneficiaries of such efforts.
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  W. Demark-Wahnefried, N. M. Aziz, J. H. Rowland, and B. M. Pinto Riding the Crest of the Teachable Moment: Promoting Long-Term Health After the Diagnosis of Cancer J. Clin. Oncol., August 20, 2005; 23(24): 5814 - 5830. [Abstract] [Full Text] [PDF]
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