Breast Cancer, Diet Composition, and Survival
By Cheryl L. Rock, PhD, RD, and Wendy Demark-Wahnefried, PhD, RD
Although the etiologic role of nutritional and dietary factors in preventing primary breast cancer has been explored extensively in epidemiological studies, relatively few studies have examined the relationship between nutritional factors and survival after breast cancer diagnosis. Women often seek nutritional guidance following the diagnosis of breast cancer, and many report that they altered their diets or other lifestyle behaviors following diagnosis and treatment.1 Recent studies indicate that 66-81% of breast cancer survivors report use of dietary supplements,2,3 and 73% report adherence to a low-fat diet.2 In one survey study, 52% of respondents (n = 531) indicated that they wanted nutritional guidance at the time of diagnosis or soon after, although few reported having ever received recommendations from their physicians.2
How nutritional factors may affect the progression of breast cancer following diagnosis is a clinically relevant issue in the management of survivors. This article will examine the relationship between diet composition and survival or recurrence (the latter two outcomes are highly correlated among women with breast cancer). No interventional studies have been completed on this subject, although some are in progress. During the past two decades, the relationships between recurrence (or overall survival) and dietary intakes (primarily dietary fat) have been examined in 13 observational studies involving cohorts of women diagnosed with breast cancer.4-16 The dietary factors examined in these studies were mainly those associated with risk for primary breast cancer. With one exception,16 these studies used dietary data collected close to the time of diagnosis.
Dietary Fat
A major issue in the interpretation of the data relating dietary fat intake to breast cancer risk or progression is that fat intake and total energy consumption always co-vary (and also typically correlate with obesity), so an independent effect of total dietary fat per se is difficult to assess accurately. All methods of self-reported dietary assessment tend to underestimate energy intake, and this bias is most evident for high-fat foods. Underreporting affects the accuracy of dietary data more among women (vs. men), those categorized as overweight, minority groups, and younger (vs. older) adults.17 Rates of intake underreporting among breast cancer survivors are similar to rates in the general population, and obese women are twice as likely as non-obese women to underreport intake.18 To minimize underreporting bias, particularly in the interpretation of data on fat intake, adjustment for energy intake is the accepted approach applied in the analysis of effects of dietary fat on risk of disease.19
Total dietary fat intake was inversely associated with disease-free or overall survival in five of 12 studies that examined this relationship.4,7,8,10,13 One study found a relationship only in women with estrogen receptor-positive tumors;13 in another study, saturated fat but not total fat intake was found to be inversely related to survival.6 Fat intake was not energy-adjusted in most of the studies that found a relationship;4,8,10 and when the investigators energy-adjusted the dietary fat data in the analysis, fat intake was unrelated to survival.4,7 In a study in which selected foods (rather than nutrients) were examined in relation to recurrence or risk for death,5 intakes of butter, margarine, and lard were directly associated with risk of recurrence, but not with risk of death.
Vegetables, Fruit, and Related Nutrients
The analysis of associations between vegetable intake (or nutrients provided by vegetables and fruit, such as carotenoids and vitamin C) have produced somewhat more consistent results. Of the eight studies that examined these dietary factors,4,6,7,11,13-16 three found a significant inverse association with risk of death,6,14,15 and one found a significant inverse association among women without metastatic disease at diagnosis (62% of the cohort), although not in the total group.16
Several biologically feasible mechanisms and supportive laboratory evidence for constituents of vegetables have been demonstrated in cell culture and animal studies. Carotenoids have retinoid-like effects on cellular differentiation and inhibit mammary cell growth.20-23 Broccoli, cauliflower, kale, and other members of the Brassica genus favorably affect estrogen metabolism via the induction of metabolizing enzymes.24 In mammals, fiber can bind to estrogen in the enterohepatic circulation and thus hinders reabsorption, adding to the multiple effects that a high-vegetable diet can exert.25,26
Alcohol
Alcohol has been consistently and positively associated with risk for primary breast cancer in epidemiological studies.27 However, in the eight studies that examined the relationship between alcohol intake and survival,4,6,7,11,13-16 no significant associations were ob-served. In the study involving the analysis of relationships based on selected foods rather than nutrients,5 beer, but not wine or liquor, was directly associated with increased risk of recurrence but not death. These findings are fairly consistent and suggest that the biological or mechanistic link between alcohol intake and mammary carcinogenesis may be relevant to primary breast cancer risk but not to recurrence or overall survival.
Phytoestrogens and Soy
Cross-country comparisons suggest that soy, rich in phytoestrogens, may have a protective effect in breast cancer.28 However, phytoestrogens can act as estrogen agonists as well as antagonists, so phytoestrogens theoretically could promote mammary neoplasia and progression of breast cancer. This issue is of most relevance to postmenopausal women who have lower levels of endogenous estrogens in the circulation that would compete for estrogen receptor binding sites. Results from cell culture studies,29 as well as in vivo feeding studies that have measured tumor burden in transplanted mice,30 have shown cancer-stimulating effects of either genistein or soy at physiologic levels. Therefore, some concern about phytoestrogen consumption among breast cancer survivors has been expressed. To date, no epidemiological or clinical studies have examined or reported the relationship between soy intake and survival in women who have been diagnosed with breast cancer (however, there does not appear to be decreased survival in Asian breast cancer patients consuming a high-soy diet). As recently reviewed,31 current data from laboratory studies are conflicting. Although moderate consumption of soy isoflavones (in amounts provided by a typical Chinese or Japanese diet) is not believed to interfere with benefits of tamoxifen or to promote cancer progression, currently there is insufficient information to make a recommendation about the use of soy foods for cancer survivors.
Dietary Supplements
Studies conducted to date have not identified dietary supplement use as being protective against recurrence in breast cancer survivors. Nutrients exhibiting protective effects in observational studies (e.g., beta carotene and vitamin C) were provided from food sources (vegetables and fruit) and consumed in amounts achievable with food choices rather than high-dose supplements.6,14,15 Because dietary supplements are relatively unregulated, it will be difficult to ascertain any effects from supplement use unless studies control for both purity and dosage and are performed with placebo controls. Certainly, clinicians should be aware of the current lack of regulation over these substances and should encourage patients who currently are taking supplements to obtain them from established manufacturers. However, given the history of previous dietary supplement trials, in which beta-carotene supplementation was found to increase the risk of lung cancer among high-risk individuals,32,33 caution is warranted. The combination and synergy of nutrients and phytochemicals contained within whole foods (i.e., vegetables, fruits, and whole grains) may be much more effective for both the primary and secondary prevention of cancer than single nutrients.
Ongoing Clinical Trials
Two large multicenter, randomized controlled trials are examining whether diet modification can influence the risk of recurrence and survival following the diagnosis of early-stage breast cancer. In the Women’s Intervention Nutrition Study (WINS), which involves 2,500 women randomized within 12 months of primary surgery, the primary dietary goal is a reduction in dietary fat intake (£ 15% energy from fat). In the Women’s Healthy Eating and Living (WHEL) study, the target population is 3,100 women randomized following completion of initial therapies and within four years of diagnosis. The primary emphasis of the WHEL study diet intervention is increased vegetable and fruit intake, with daily dietary goals of five vegetable servings, 16 ounces of vegetable juice, three fruit servings, 15-20% energy from fat, and 30 g dietary fiber. In both of these studies, participants will be followed for an average of at least six years; results are anticipated after study completion in 2004 (WHEL) and 2005 (WINS).
Current Recommendations
Although randomized controlled trials have not yet been completed on the effect of diet on breast cancer, there is no harm and possible benefit in encouraging a diet with nutrient- and phytochemical-rich vegetables and fruit, which provides an adequate intake of multiple constituents, including vitamins and fiber.
The risk of morbidity and mortality from causes other than breast cancer should be considered when making dietary recommendations for breast cancer survivors, especially those diagnosed with early-stage cancers. Diets that emphasize vegetables, fruit, whole grains, fiber, and low-fat dairy foods and are low in saturated fat are associated with decreased risk of all-cause mortality in women.34 Sufficient dietary calcium and vitamin D and increased physical activity are particularly appropriate recommendations to maintain bone health.
Dr. Rock is Associate Professor, University of California, San Diego, Department of Family and Preventive Medicine, Cancer Prevention and Control Program; Dr. Demark-Wahnefried is Associate Professor, Department of Surgery, Duke Comprehensive Cancer Center, Cancer Prevention, Detection, and Control Program, Durham, NC.
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Rock CL, Demark-Wahnefried W. Breast cancer, diet composition, and survival. Altern Ther Women's Health 2002;4:9-12.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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