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,
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
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
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 (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. Recently, Boyd et al have shown that breast duct density,
as measured by mammography, is positively affected by a low-fat diet.
It is believed that a dense ductal pattern is associated with an elevated
risk for breast cancer.
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.
1. Kakizoe T (ed): Figures on Cancer in Japan. Tokyo, Japan, Foundation
for Promotion of Cancer Research, 1995.
2. Ries LAG, Miller BA, Hankey BF, et al (eds): SEER Cancer Statistics
Review, 1973-1991: Tables and Graphs. Bethesda, Maryland, National Cancer
Institute, NIH publication no. 94-2789, 1994.
3. Wynder EL, Kajitani T, Kuno J, et al: A comparison of survival rates
between American and Japanese patients with breast cancer. Gynecol Obstet
4. Boyd NF, Greenberg C, Lockwood G, et al: The effects at 2 years of
a 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 Institute
For Cancer Research 1996 Research Conference poster abstract booklet.