Low-Fat Diet and Risk of Breast Cancer

Abstract

To the Editor: The Women’s Health Initiative (WHI) randomized controlled trial of a low-fat dietary pattern by Dr Prentice and colleagues found a reduced risk of invasive breast cancer that did not quite reach statistical significance. An important issue is not whether the results are significant but whether any reduction in risk should be attributed to lower fat intake or to the reduction of body weight observed in the intervention group and generated by lower energy intake in that group. As seen in Table 2 of the article, over a 6-year period the average body weight reduction was more pronounced in the intervention group than in the comparison group by 1.4 kg (the mean value of the differences in weight changes of 2.2, 1.3, and 0.8 kg at years 1, 3, and 6, respectively). Huang et al found that among nonusers of hormone therapy, a weight gain of more than 20 kg compared with stable weight was associated with a relative risk of 1.99 for development of breast cancer over 16 years. A crude calculation would suggest that a weight change of 1 kg may be associated with a change in the relative risk of 0.049 (the excess risk of 0.99 divided by 20); if so, a reduction of body weight by 1.43 kg would be associated with a risk reduction of 7%, similar to the 9% reduction found in the intervention group of the WHI trial. This at least merits consideration in the interpretation of the results of this study. The mechanism linking increased body weight to breast cancer risk invokes increased aromatization of androstenedione to estrone in adipose tissue. Estrogens among postmenopausal women are likely to function as growthenhancing compounds with fairly short latency, comparable with that observed after cessation of hormone therapy ( 1 year). If an effect of fat reduction beyond that mediated by weight reduction were to be proposed on the basis of the results of the trial, body weight reduction would have to be controlled for in the analysis.