Diet and Breast Cancer Recurrence
By Diane L. McKay, PhD, FACN. Dr. McKay is an Adjunct Assistant Professor, Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, and Scientist, Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Boston; she reports no financial relationships relevant to this field of study.
Breast cancer is the most commonly diagnosed cancer among women worldwide, and the second most common cause of cancer mortality among women in the United States.1 According to the American Cancer Society, death rates from breast cancer have steadily decreased in women since 1990, due to a combination of earlier detection and improved treatment.2 However, among breast cancer survivors, the long-term risk of recurrence is always a concern. Diet, exercise, and body fat are known to play a central role in both cancer prevention and recurrence, but a limited number of clinical studies have examined the potential benefits of dietary modification on breast cancer prognosis.3,4
Mechanisms of Action
Breast cancer is a hormone-related disease, and factors that modify the risk of this cancer will differ depending on whether it is diagnosed before or after menopause. Early life events, including diet, and factors that affect hormone status can modify breast cancer risk. Life events that protect against breast cancer include late menarche, early pregnancy, bearing children, and early menopause, all of which reduce the number of menstrual cycles and, therefore, lifetime exposure to estrogen.1
Factors that modify the risk of total body fatness and abdominal fatness, including physical activity and the energy density of foods and drinks, are also associated with breast cancer risk.1 There are many known interactions between nutritional factors and physiological processes involved in the initiation and proliferation of cancer cells. For example, retinoids, vitamins A and D, folate, coenzyme Q10, zinc, and selenium support DNA repair mechanisms, while phytochemical compounds, including polyphenols, carotenoids, and organosulfur compounds, promote apoptosis. Since fruits and vegetables are low in calories and fat, and a good source of these vitamins, minerals, and phytochemicals, they are recommended as part of an overall healthy diet to reduce the risk of many chronic diseases including cancer.
Clinical studies
The results of two large randomized trials examining the effects of diet on breast cancer recurrence have been published within the last two years. In the Women's Intervention Nutrition Study (WINS),3 2437 women with early-stage breast cancer who received conventional cancer management were randomly assigned to either a low-fat dietary intervention (with a goal of 15% of total calories from fat) or no dietary intervention (control) within one year of their initial diagnosis. The mean dietary fat intake in the intervention group after one year was reduced from 57.3 g (29.6% of calories) at baseline to 33.3 g (20.3%, P < 0.0001), while the control group lowered their fat intake from 56.3 g (29.6%) to 51.3 (29.2%, P < 0.0001). Even though subjects in both groups significantly lowered their fat intake, the 19 g (8% of calories) difference in fat intake between groups was maintained throughout the 5-year follow-up (P < 0.0001), resulting in a 2.7 kg lower mean body weight in the intervention group (P = 0.005). After five years, 9.8% of women in the low-fat intervention group reported relapse events compared with 12.4% of women in the control group (HR = 0.76, 95% CI = 0.60-0.98, P = 0.077 for stratified log rank and P = 0.034 for adjusted Cox analysis). Relapse events included either lateral breast cancer recurrence or new contralateral breast cancer. There was no difference in overall survival between the two groups (HR = 0.89, 95% CI = 0.65-1.21, P = 0.56). In a subgroup analysis, the dietary intervention did have a greater effect on relapse-free survival among women with estrogen receptor (ER)-negative cancer (HR = 0.58, 95% CI = 0.37-0.91) than women with ER-positive cancer (HR = 0.85, 95% CI = 0.63-1.14).
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The Women's Healthy Eating and Living (WHEL)4 trial assessed whether decreased dietary fat plus increased fruit and vegetable consumption influenced breast cancer recurrence or survival. All 3008 women in this study were treated for early stage breast cancer and enrolled within four years of their initial diagnosis. Subjects were randomized to receive either an intensive dietary intervention promoting the daily consumption of 5 vegetable servings with an additional 16 oz of vegetable juice, 3 fruit servings, 30 g fiber, and ≤ 15-20% of calories from fat (intervention group), or print materials describing the 5-A-Day diet5,6 recommendations of 5 servings of vegetables and fruits, > 20 g fiber, and < 30% total calories from fat per day (control group). Changes in fruit and vegetable consumption were validated by measuring plasma carotenoid concentrations. After a mean follow-up period of 7.3 years, 16.7% of women in the low-fat, high fruit and vegetable intervention group experienced an invasive breast cancer event compared with 16.9% of women in the control group (HR = 0.96, 95% CI = 0.80-1.14, P = 0.63). Similarly, no difference in overall survival was observed between the two groups (HR = 0.91, 95% CI = 0.72-1.15, P = 0.43).
Conclusion
The results of the WINS and WHEL studies appear to be contradictory, as a reduction in breast cancer recurrence was observed in one trial but not the other. Neither trial found an effect of diet on breast cancer survival. One reason for this discrepancy may be the lower mean between-group difference in fat intake attained in the WHEL trial compared with WINS (3.5% vs 8.0% difference in calories from fat, respectively). Another possible explanation for the discrepancy may be the moderate weight loss observed in WINS subjects, but not in WHEL subjects (2.7 kg vs. 0.4 kg, respectively). Taken together, these data support findings from observational studies suggesting that a high level of obesity, weight gain, or both after diagnosis is adversely associated with breast cancer recurrence and overall survival.7
Increased fruit and vegetable consumption had no effect in the absence of significant dietary fat reduction or weight loss. However, it is arguable that the increase in fruit and vegetable consumption attained in the WHEL study was not as great as it might have been. Observational studies do suggest that a diet rich in fruits and vegetables is associated with a reduced risk of some cancers, but the evidence for a protective effect against breast cancer or its recurrence is not convincing at this time. Nutritional factors that are more strongly associated with breast cancer risk include alcohol consumption, physical activity level, total body fat, and abdominal fat.1
Recommendation
All patients should be advised to maintain a healthy weight by engaging in regular physical activity and consuming a diet low in energy density. Recommendations to reduce dietary fat intake and increase fruit and vegetable consumption are consistent with current guidelines to reduce chronic disease risk, but may have only a modest effect on survival rates in breast cancer patients.
References
1. World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: A Global Perspective. Washington DC: AICR, 2007.
2. American Cancer Society. Cancer Facts & Figures 2007. Atlanta: American Cancer Society; 2007.
3. Chlebowski RT, et al. Dietary fat reduction and breast cancer outcome: Interim efficacy results from the Women's Intervention Nutrition Study. J Natl Cancer Inst 2006;98:1767-1776.
4. Pierce JP, et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: The Women's Healthy Eating and Living (WHEL) Randomized Trial. JAMA 2007;298:289-298.
5. National Cancer Institute. Action Guide for Healthy Eating. Bethesda, MD: National Cancer Institute;1995.
6. National Cancer Institute. Eat 5 Fruits and Vegetables a Day. Washington, DC: National Cancer Institute;1995.
7. Gapstur SM, Khan S. Fat, fruits, vegetables, and breast cancer survivorship. JAMA 2007;298: 335-336.
McKay DL. Diet and Breast Cancer Recurrence. 2008;11:25-28.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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