Breast Cancer Prevention Strategies

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

Although dietary intake is mentioned as one possible means for breastcancer prevention, its effects are understated. Epidemiologists searchfor the reasons behind extreme variations in the incidence and mortalityof disease--an endeavor that is likely to tell us more about etiologicfactors than would small differences. With regard to breast cancer, whilewe and others have researched and written about such risk factors as ageat menarche and menopause, parity and age at first pregnancy, weight andalcohol consumption, physical activity and heredity, estrogen supplementsand radiation, it would seem clear that none of these variables, eithersingly or taken together, can account for the major differences in incidenceand death rates that exist between Japan and the United States (Figure1).[1,2]

These differences are particularly striking in postmenopausal women,and can best be explained by dietary intake, as seen in Table1, which charts food consumption data from 1951 through 1985. The lowintake of meat and dairy products among the Japanese is especially noteworthy.Initially, it was thought that perhaps the lower rates of breast cancerin the Japanese are due to genetic differences. However, the fact that,among Japanese women who move to Hawaii, breast cancer rates by the secondgeneration approach those seen in US women indicates that environmentalfactors, such as diet, play a determining etiologic role.

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

Fatty Acids and Breast Cancer Progression

The concept that diet is an important factor is supported by large-scaleanimal studies demonstrating that certain types of fatty acids significantlyaffect the promotion and progression of breast cancer. The diets givenin these studies are isocaloric, so that the findings cannot be due toexcess calories. Furthermore, mechanistic studies provide biologic validityfor the link between nutrition and breast cancer that has been observedin both animal and human studies.

Nutritional assessment studies, both cohort and case-control, have yieldedmixed results, which is not unexpected. First, when we compare breast cancerpatients with controls, it needs to be recognized that the control patientshave 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 dietaryrecall, or 4-day dietary records, dietary histories need to be viewed withcaution.

Women's Intervention Nutrition Study

In view of these data, we are currently conducting the Women's InterventionNutrition Study in postmenopausal stage I and II breast cancer patientstreat-ed in standard fashion with either tamoxifen (Nolvadex) or chemotherapy.This trial, being conducted at approximately 30 cancer centers, is investigatingwhether a low-fat diet (15% of total calories) can affect the recurrencerate of breast cancer, as compared with a diet in which 30% of caloriescome from fat. Among the 2,500 patients required for the study, approximately900 patients have been accrued, and significant differences have alreadybeen 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 recallappears to be an adequate nutritional assessment. Furthermore, these dataare also being confirmed by an assay of serum fatty acids as dietary biomarkersin women participating in the study.

This trial is based not only on epidemiologic and animal studies butalso on the finding that survival among postmenopausal breast cancer patientstreated with tamoxifen is twice as high among women in Japan as in Westerncountries.[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 elevatedrisk for breast cancer.

Summary

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

References:

1. Kakizoe T (ed): Figures on Cancer in Japan. Tokyo, Japan, Foundationfor Promotion of Cancer Research, 1995.

2. Ries LAG, Miller BA, Hankey BF, et al (eds): SEER Cancer StatisticsReview, 1973-1991: Tables and Graphs. Bethesda, Maryland, National CancerInstitute, NIH publication no. 94-2789, 1994.

3. Wynder EL, Kajitani T, Kuno J, et al: A comparison of survival ratesbetween American and Japanese patients with breast cancer. Gynecol Obstet111:196-200, 1963.

4. Boyd NF, Greenberg C, Lockwood G, et al: The effects at 2 years ofa low-fat high-carbohydrate diet on radiological features of the breast:Results from a randomized trial (poster abstract 6). Dietary Fat and Cancer:Genetic and Molecular Interactions. Washington, DC, American InstituteFor Cancer Research 1996 Research Conference poster abstract booklet.