Breast Cancer Prevention Strategies

In this issue, Love and Vogel bring attention to the fact that most breast cancers are not inherited but are the result of several, varied hormonal influences. This is an important message because prevention of breast cancer for some women can be accomplished by hormone manipulation from moderate exercise, maintaining low body mass, abstention from alcohol(Drug information on alcohol), and lactation. The authors discuss the physiologic role of delayed pregnancy but avoid the issue in terms of preventive strategy. Many women choose to delay pregnancy in pursuit of career development for economic reasons. This makes for a difficult choice in terms of breast cancer risk, but one that should be addressed. The article proposes that lobular maturation and exposure of the breast to hormones are two key processes in breast cancer. Indeed, emerging data also suggest that excess hormonal exposure in utero may influence adult breast cancer risk.

Although dietary intake is mentioned as one possible means for breast cancer prevention, its effects are understated. Epidemiologists search for the reasons behind extreme variations in the incidence and mortality of disease--an endeavor that is likely to tell us more about etiologic factors than would small differences. With regard to breast cancer, while we and others have researched and written about such risk factors as age at menarche and menopause, parity and age at first pregnancy, weight and alcohol consumption, physical activity and heredity, estrogen supplements and radiation, it would seem clear that none of these variables, either singly or taken together, can account for the major differences in incidence and death rates that exist between Japan and the United States (Figure 1).[1,2]

These differences are particularly striking in postmenopausal women, and can best be explained by dietary intake, as seen in Table 1, which charts food consumption data from 1951 through 1985. The low intake of meat and dairy products among the Japanese is especially noteworthy. Initially, it was thought that perhaps the lower rates of breast cancer in the Japanese are due to genetic differences. However, the fact that, among Japanese women who move to Hawaii, breast cancer rates by the second generation approach those seen in US women indicates that environmental factors, such as diet, play a determining etiologic role.

With respect to weight, premenopausal breast cancer is associated with low body weight, whereas postmenopausal women with breast cancer tend to be somewhat, but not excessively, overweight.

Fatty Acids and Breast Cancer Progression

The concept that diet is an important factor is supported by large-scale animal studies demonstrating that certain types of fatty acids significantly affect the promotion and progression of breast cancer. The diets given in these studies are isocaloric, so that the findings cannot be due to excess calories. Furthermore, mechanistic studies provide biologic validity for the link between nutrition and breast cancer that has been observed in both animal and human studies.

Nutritional assessment studies, both cohort and case-control, have yielded mixed results, which is not unexpected. First, when we compare breast cancer patients with controls, it needs to be recognized that the control patients have a relatively high fat diet as well. Also, because of inherent problems, such as reporting and recall biases associated with nutritional assessments, whether they are based on food frequency questionnaires, 24-hour dietary recall, or 4-day dietary records, dietary histories need to be viewed with caution.

Women's Intervention Nutrition Study

In view of these data, we are currently conducting the Women's Intervention Nutrition Study in postmenopausal stage I and II breast cancer patients treat-ed in standard fashion with either tamoxifen(Drug information on tamoxifen) (Nolvadex) or chemotherapy. This trial, being conducted at approximately 30 cancer centers, is investigating whether a low-fat diet (15% of total calories) can affect the recurrence rate of breast cancer, as compared with a diet in which 30% of calories come from fat. Among the 2,500 patients required for the study, approximately 900 patients have been accrued, and significant differences have already been seen in fat intake between years 1 and 2 in patients vs controls. In the case of large groups with marked dietary differences, 24-hour recall appears to be an adequate nutritional assessment. Furthermore, these data are also being confirmed by an assay of serum fatty acids as dietary biomarkers in women participating in the study.

This trial is based not only on epidemiologic and animal studies but also on the finding that survival among postmenopausal breast cancer patients treated with tamoxifen is twice as high among women in Japan as in Western countries.[3] Recently, Boyd et al have shown that breast duct density, as measured by mammography, is positively affected by a low-fat diet.[4] It is believed that a dense ductal pattern is associated with an elevated risk for breast cancer.

Summary

In summary, we believe that dietary fats, especially saturated and unsaturated fats rich in omega-6 fatty acids, although not fish oils or monounsaturated fats, significantly affect the promotion and progression of breast cancer. We suggest to our colleagues in oncology and those engaged in laboratory studies to pursue these leads in both experimental and clinical settings.