Focus on Cancer Prevention

10/17/02 - A low fat diet rich in omega-3 fatty acids derived from fish oil, which may increase serum estradiol levels, alters the make-up of the mammary gland and reduces breast cancer risk, according to a study conducted by researchers at Georgetown University.

"The timing of estrogen exposure is essential in determining its effect on breast cancer risk," according to Dr Leena Hilakivi-Clarke, professor of oncology and director of tumor biology, and lead investigator of the study. "Exposure to estrogen around puberty has been demonstrated to decrease the risk of developing breast cancer later in life; however, this is not an optimal chemoprevention method."

The study, designed to identify potential dietary methods to alter pre-puberty estrogen levels, compared low fat (16 per cent energy) or high fat (39 per cent energy) diets composed of either omega-3 or n-6 polyunsaturated fatty acids (PUFAs) in menhaden (fish) oil or corn oil, respectively, in nursing rats and their female offspring. Both the low and high fat fish oil diets increased circulating estrogen levels, but only the low fat diet reduced breast cancer risk.

The study was one of several presented at this week's American Association for Cancer Research's (AACR) first annual Frontiers in Cancer Prevention Research meeting, which aimed to set the stage for further exploration into the connection between cancer and obesity.
Another study presented by researchers at the National Cancer Institute (NCI) found that prevention of obesity through dietary interventions, such as calorie restriction or occasional fasting, inhibits breast cancer growth.

The study used mice with inherent alterations in two important and commonly altered genetic pathways in the human cancer process. Their mice were deficient in p53 (a tumor suppressor gene that acts like a brake to protect against uncontrolled cell proliferation) and also had high mammary gland expression of Wnt-1 (an oncogene that acts like an accelerator to enhance cell proliferation).

Female p53-deficient Wnt-1 transgenic mice provided with unlimited access to food became obese and rapidly developed fatal mammary tumors, while mice provided with fewer calories each day, or fasted one day per week, lived tumor-free two to three times longer than the obese mice.
"Reduced serum levels of insulin-like growth factor (IGF)-1, which is a diet-responsive growth factor, were associated with the reduction in calorie intake and inhibition of mammary tumors in these mice," said Stephen Hursting, Ph.D., deputy director of the Office of Preventive Oncology, Division of Cancer Prevention, NCI and lead investigator of the study.

"These observations suggest that IGF-1 may be an important biological mediator of the protection afforded by the obesity-preventing interventions."

Hursting's group is also currently testing whether exercise is effective in this model.

Other research from the Hormel Institute at University of Minnesota found that a healthy diet combined with periods of calorie restriction may provide more protection against breast cancer than a constant low calorie diet.

"The manner in which caloric restriction is implemented may play an important role in the development of breast cancer," according to Margot Cleary, lead investigator of the study. "There appears to be a point above which calorie intake stimulates the growth of breast cancer and can potentially override, to some degree, the protective effect of severe caloric restriction."

Mammary mouse tumor virus (MMTV)–TGFa mice (TGFa regulates growth) were fed either an ad lititum (as desired; AL), a calorie restricted (CR) or an intermittent caloric restriction/refeeding (IR-R) diet. The incidence of mammary tumors was 84 per cent in AL mice, 37 per cent for the CR mice, and 15 per cent for the IR-R mice. Age of mammary tumor detection was significantly extended in the IR-R mice to 79.4 weeks of age compared to 67.9 weeks of age for AL mice. In addition, AL mice were younger at death than were both IR-R and CR mice.

According to the American Cancer Society, more than 203,500 new cases of breast cancer will be diagnosed and more than 39,600 women will die in 2002. Breast cancer is the second leading cause of cancer-related death in women.

*These statements have not been evaluated by the Food and Drug Administration

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