Animal models have revealed that calorie restriction extends life and protects against tumors, including mammary carcinogenesis. In humans, breast tissue appears to be particularly susceptible to carcinogenic processes in early life and before the first pregnancy. Michels and Ekbom conducted a retrospective cohort study of the impact of caloric restriction on the development of breast cancer. Specifically, they studied women with anorexia nervosa severe enough to require hospitalization to determine if these women had a lower incidence of breast cancer than was expected in the general population.

The authors used data from several Swedish Registries to find woman who were hospitalized for anorexia before age 40 between 1965 and 1998. Of the 7,303 women identified, 31 were excluded because of a cancer diagnosis before discharge. A standardized incidence ratio calculated the observed number of first primary cancer cases as a ratio to the number of cases expected. The modifying relationship of parity on breast cancer incidence was assessed by dividing women into parous and nulliparous groups.

In this cohort, 52 women were identified with any type of cancer during 96,887 person-years of follow-up between 1965 and 2000. The standardized incidence ratio for breast cancer was 0.47 among women who were diagnosed with anorexia before 40 years of age. These women had a 53 percent lower incidence of breast cancer than women in the Swedish general population. None of the women with anorexia diagnosed before 20 years of age developed breast cancer. The number of expected cases was 2.7. In the group including women aged 20 to 29 years, the actual and expected cases were 4.0 versus 6.4, respectively. In the group aged 30 to 39 years, there were 3.0 actual cases and 5.7 expected cases.

In the 73 percent of women who remained nulliparous, the standardized incidence ratio for breast cancer was 0.77 during 78,984 person-years of follow-up; the ratio was 0.24 during 17,903 person-years of follow-up in the parous group. The reduced incidence of breast cancer in these groups was 23 percent in nulliparous women and 76 percent in parous women.

The authors found a significant decrease in breast cancer incidence in the cohort of women with a hospital discharge diagnosis of anorexia compared with the Swedish general population, with additional protection conferred by subsequent pregnancy. These findings are consistent with observations that in developing countries where food is scarce but there is a high birth rate, women have a lower incidence of breast cancer than in affluent countries.

The impact of caloric restriction in the early period of breast development may be particularly important, as may differentiation of breast tissue during pregnancy in conferring a protective effect. The authors call for further research to determine if the lower incidence of breast cancer associated with anorexia is due to caloric restriction on breast cell development, to amenorrhea and lack of estrogen, or to a decreased level of growth factors.