By Lynn Keegan, RN, PhD, HNC, FAAN, and Gerald T. Keegan, MD, FACS
Breast cancer is the second most common cancer in the world and the most common cancer in women. Incidence rates are about five times higher in western countries than in developing countries and Japan.1 International and regional variation may be related to reproductive risk factors, such as age at menarche, parity and age at birth, and breastfeeding,2,3 but differences in dietary habits and physical activity also might be contributing factors. Multiple studies have suggested that obesity increases risk of breast cancer in postmenopausal women by around 50%. Peculiarly, although obesity in postmenopausal women has been found to increase risk of breast cancer, the opposite has been found in premenopausal women where obesity is associated with a moderate risk reduction.
The question as to whether high fat intake increases the risk of breast cancer has been quite controversial and the results have been conflicting. Some studies have even suggested that there is no causative link between fat intake and the development of breast cancer.4 The converse hypothesis—that low fat intake is associated with a lower breast cancer risk—has been demonstrated recently, but in this study dietary fat alone was not the sole determinant, since it was found that the combination of high fiber and low fat had the lowest risk.5 A diet containing more than 30% of the total calories from fat could be considered a high-fat diet. Different methods of assessing fat intake have further confused the data.6 The emerging information seems to suggest that saturated fat found in butter, high-fat milk, and meat, and fat used as a food additive rather than fats in general may be the offending culprit.7
Table 1: Comparison of high-fat and low-fat foods
Mechanisms of Action
Hormonal mechanisms as well as genetic and environmental factors play key roles in the etiology of breast cancer. One commonly proposed mechanism of action is related to the increased serum concentrations of free estradiol.3 Other hormonal factors, including insulin-like growth factors (IGF-1) and insulin itself, may be interacting causative factors in the development of breast cancer. Although dietary fat has not been shown conclusively to change the levels of circulating estrogens,8 obese women with more adipose tissue have more aromatase, a substance that catalyses the conversion of androgens to estrogens. This conversion becomes the main source of endogenous estrogens in postmenopausal women.9 Although not directly related, the combination of excess energy intake secondary to consumption of foods with a high glycemic index and low physical activity may lead to insulin resistance and hyperinsulinemia. Hyperinsulinemia can increase the risk of breast and other cancers due to the mitogenic effects of insulin.10,11
A difficulty with many studies is that the mechanism of action of fat intake on breast cancer is likely to be different in premenopausal vs. postmenopausal women. Studies on the relationship of body mass to the risk of breast cancer are complex and show opposing effects of a high basic metabolic index on premenopausal and postmenopausal risk.12,13 Studies actually have shown a U-shaped relationship between relative weight in adolescence and later risk of breast cancer. Women who were either much heavier or much thinner than average were at reduced risk.14 Multiple reasons could be suggested for this variance including the common element of delayed menarche as well as completely different mechanisms producing the protective effect.15
Clinical Trials—Animal Studies
In experimental animals, restriction of caloric intake has been a very effective tool in reducing spontaneous tumor recurrence. Reduced caloric intake in general, not necessarily just fat restriction, is accompanied by lower levels of circulating insulin, IGF-I and II, and epidermal growth factor. In addition, with the caloric restriction there is modification of the cellular responsiveness to estrogens, enhancement of the immunologic response, lower rates of cell proliferation, increased DNA repair, reduced expression of oncogenes, and enhanced expression of the tumor suppressive genes.15-17 Theoretically, the modification of these factors could contribute to a lower incidence of breast cancer. The evidence, however, for the role of fat intake and changes in the risk of breast cancer does not stand up to close scrutiny.
A study in Hong Kong using a Noble rat model of sex-hormone-induced cancer to examine the effect of a high-fat diet on the incidence and latency of prostate and mammary cancers in male and female animals found a very high incidence of hormone-induced cancers of both prostate and mammary gland, irrespective of diet.18 Alpha-tocopherol levels also were measured in female breast tissue to determine whether a high intake of polyunsaturated fatty acids depleted the antioxidant defense in target tissues, possibly suggesting a potentiating mechanism for carcinogenesis. The authors concluded that not only was there was no significant association between fat intake and the development of either prostate or breast cancer, but breast alpha-tocopherol was unaffected by dietary fat. The results did not support a role for dietary fat in promoting sex-hormone-induced prostate or mammary carcinogenesis.
Clinical Trials—Human Studies
Human studies are far less definitive in their conclusions. Many studies are impaired by not making a differentiation between saturated and unsaturated fats.
Currently the best data come from the European Prospective Investigation of Cancer and Nutrition Norfolk study, which tried to make this distinction by using a detailed analysis of food diaries in more than 1,300 women.6 The researchers concluded that women who consumed more than 90 g/d of fat had twice the risk of breast cancer of those who had eaten less than 40 g/d. Data from a segment of the Nurses’ Health Study from 1991 to 1999 based on questionnaires on dietary habits concluded a significant premenopausal risk from the intake of animal and dairy products.7 The study found no relationship between breast cancer risk and the amount of vegetable fat intake.
A recently published comprehensive statistical analysis on the relationship of caloric restriction and breast cancer in women hospitalized for anorexia nervosa concluded that severe caloric restriction in humans conferred protection from invasive breast cancer.15 Low caloric intake prior to first birth followed by subsequent pregnancy appeared to be associated with an even more pronounced reduction in risk. This study confirmed an earlier finding in prepubertal girls who were exposed to the Norwegian famine in World War II, who consumed 22% fewer calories, and who subsequently were found to have a lower rate of breast cancer than women from earlier or later birth cohorts.19 Although low caloric intake may correlate with low fat intake, the presumed positive correlation does not necessarily indicate causality.
Conclusion
The relationship of fat intake to breast cancer is not fully established either in terms of demographics or mechanisms of action. The best current studies suggest that saturated fats from red meat and dairy products are related to an increased risk of breast cancer. No clear evidence incriminates vegetable fat intake in increased risk. Multiple other factors play significant interactive roles.
Recommendations
Health professionals should advise their patients of the importance of maintaining a low fat, low-glycemic index diet. Patients need to be reminded of the importance of fiber intake and regular physical exercise. Patients with a family history of breast cancer need to continue to have regular examinations and routine mammograms.
Gerald T. Keegan, MD is Emeritus Staff, Scott & White Clinic and Hospital, and former Professor of Surgery (Urology), Texas A&M University School of Medicine.
References
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8. Holmes MD, et al. Dietary fat intake and endogenous sex steroid hormone levels in postmenopausal women. J Clin Oncol 2000;18:3668-3676.
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12. Van den Brandt PA, et al. Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 2000;152:514-527.
13. Friedenreich CM. Review of anthropromorphic factors and breast cancer risk. Eur J Cancer Prev 2001;10: 15-32.
14. Coates RJ, et al. Risk of breast cancer in young women in relation to body size and weight gain in adolescence and early adulthood. Br J Cancer 1999;81:167-174.
15. Michels K, et al. Caloric restriction and incidence of breast cancer. JAMA 2004;291:1226-1230.
16. Dirx MJM, et al. Energy restriction and the risk of spontaneous mammary tumors in mice: A meta- analysis. Int J Cancer 2003;106;766-770.
17. Fernandes G, et al. Dietary lipids and calorie restriction affect mammary tumor incidence and gene expression in mouse mammary tumor virus/v-Ha-ras transgenic mice. Proc Natl Acad Sci U S A 1995;92: 6494-6498.
18. Leung G, et al. No effect of a high-fat diet on promotion of sex hormone-induced prostate and mammary carcinogenesis in the Noble rat model. Br J Nutr 2002; 88:399-409.
19. Tretli S, et al. Lifestyle changes during adolescence and risk of breast cancer: An ecologic study of the effect of World War II in Norway. Cancer Causes Control 1996;7:507-512.
Keegan L, Keegan GT. The role of fat intake in breast cancer. Altern Ther Women's Health 2004;6(7):49-53.
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