A new study presented at the 2011 Era of Hope breast cancer conference has reported that periods of severe calorie restriction accompanied by weight loss prevent mouse mammary tumor development even if the weight is regained. Sustained low calorie diets have been reported to prevent development of mammary tumors in rodents, however a long-term low calorie diet is not a realistic prevention strategy for most people. Also, suppose weight is lost through calorie restriction and then regained or partially regained? Few studies have investigated the effect of weight regain after caloric restriction on mammary tumor development. The authors used mice who have been bred to develop mammary tumors spontaneously to evaluate the effects of chronic caloric restriction compared to intermittent calorie restriction (periods of weight loss/regain) on mammary tumor development in four studies.

In the first three studies, mice were fed either (1) a standard diet without restriction ("at will group"); (2) an intermittent calorie restriction schedule consisting of three weeks of 50% of the calories consumed by the at will group, followed by three weeks of refeeding; or (3) chronic caloric restriction ("chronic restriction group"). In Study 4, the fat content of the diets was increased to determine whether fat intake during refeeding influenced mammary tumor development. All of the mice were euthanized after having completed at least 11 feeding cycles. Mammary tumor incidence and serum insulin-like growth factor-I (IGF-I) levels were determined in all studies. IGF-1 is required for mammary development at puberty and has been implicated in increased risk of breast cancer. In Studies 3 and 4, circulating levels of the fat hormones leptin and adiponectin were also measured. Leptin has been shown to stimulate breast cancer cell proliferations whereas adiponectin suppresses it.

In Studies 1 through 3, mammary tumor incidence was found to vary between 68% to 84% for mice eating at will compared to 36% to 44% to for mice on restricted diets and only 3% to 15% for mice on intermittent calorie restriction schedules. Mice in the chronic caloric restriction and at will groups that eventually developed mammary tumors were found to have higher IGF-I levels before any mammary tumors were detected compared to mice that remained tumor free. Mice in the intermittent calorie restriction group had lower serum IGF-I and leptin levels than at will and chronic caloric restriction mice and their adiponectin to leptin ratio increased. In Study 4, consumption of a higher fat diet during refeeding was not found to interfere with the protective effect of intermittent calorie restriction. The Study 4 mammary tumor incidence rates were 67% (at will group), 52% (chronic caloric restriction), and 4% (intermittent calorie restriction). The authors conclude that intermittent calorie restriction consistently prevents mammary tumor development to a greater extent than chronic caloric restriction despite identical overall calorie and nutrient intakes. Periods of intermittent calorie restriction are associated with reduced serum IGF-I and leptin levels and elevated adiponectin to leptin ratio, all of which may inhibit cell proliferation. The study results indicate that periods of severe calorie restriction accompanied by weight loss have a protective effect on mammary tumor development even if the weight is regained.