The manner in which calories are restricted impacts mammary tumor cancer prevention

Abstract

Although treatments for breast cancer have improved and long-term survival after diagnosis is now common, prevention of the disease is the ultimate goal. Weight loss or weight maintenance is one approach that has been recommended to reduce the risk of breast cancer, particularly for peri/postmenopausal women. This approach is supported by decades of data indicating that calorie restriction prevents spontaneous and chemically induced mammary tumor development in rodents. In most cases, calorie restriction was implemented by a consistent daily reduction of calories, i.e. chronic calorie restriction (CCR). There have also been several studies where periods of reduced caloric intake were followed by periods of refeeding, i.e. intermittent calorie restriction (ICR), resulting in the prevention of spontaneous mammary tumorigenesis. In most of the early studies, there were no direct comparisons of CCR to ICR. One study using moderate calorie restriction in a chemically induced breast cancer rat model found a slight increase in mammary tumor incidence compared with ad libitum fed and CCR rats. However, recently, it has been demonstrated in several transgenic mouse models of breast cancer that ICR consistently provided a greater degree of protection than CCR. This review will provide a detailed comparison of ICR and CCR for breast cancer prevention. It will also examine potential mechanisms of action that may include periods of reduced IGF-I and leptin as well as an increase in the adiponectin:leptin ratio. Application of this approach to at-risk women may provide an approach to lower the risk of breast cancer in overweight/obese women.

Keywords: Animal models; breast cancer; calorie restriction; intermittent calorie restriction.

Figure 1

Comparison of ad libitum feeding versus chronic calorie restriction (CCR) feeding versus intermittent calorie restriction (ICR) feeding on mammary tumor incidence (%) in MMTV-TGF-α mice. (a) Study 1: intervention started at 10 weeks of age. ICR mice calorie restricted by 50% for 3 weeks followed by 3 weeks of ad libitum refeeding until 80 weeks of age (1 week of refeeding). Calorie intake for ICR and CCR mice reduced ~20%.[41] (b) Study 2: intervention started at 10 weeks of age. ICR mice calorie restricted by 50% for 3 weeks followed by 3 weeks of ad libitum refeeding until either 79 (after final restriction period) or 80 weeks of age (1 week of refeeding). Calorie intake for ICR and CCR mice reduced 11% and 14%, respectively.[42] (c) Study 3: intervention started at 10 weeks of age. ICR mice calorie restricted at 50% for 3 weeks followed by 3 weeks of controlled refeeding (i.e., matched to ad libitum fed mice's intake) until 79 (after final restriction period) or 82 weeks of age (after the final 3 weeks of refeeding). Calorie intake for ICR and CCR reduced ~25%.[43] For each study, the values are all different by Chi square analyses