Diet and breast cancer: trial and error?

The risk of developing breast cancer in females is determined by characteristics of hormone- and pregnancy-related tissue growth and development and mechanistic interactions between carcinogens and molecular targets and clonal selection of cell lines. Animal models have substantiated the idea that breast tissue may have periods of increased sensitivity to carcinogens and that dietary fat, and particularly energy intake, affect cancer risk. In epidemiological research, ecological studies clearly demonstrated positive associations between dietary fat and breast cancer risk, but individual-based case-control studies and cohort studies did not support a causal interpretation. The debate is now whether the ecological fallacy or biases in analytical epidemiology account for the apparent discrepancy, and the character of the debate is mainly of a methodological nature. Ecological and analytical studies, however, are fundamentally different with respect to the time- and age-axes considered. The lack of association in analytical studies addressing late-stage carcinogenesis may be attributed to exposures being relevant earlier in life. Analytical studies that integrate insights relating to periods of increased tissue susceptibility and mechanistic models of carcinogenic action may be fruitful in producing new outlooks for breast cancer prevention.