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TitleApproaches to Breast Cancer Prevention
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Page 1

APPROACHES TO BREAST
CANCER PREVENTION

Page 2

Developments in Oncology

Volume 62

Page 122

Diet, Body Size and the Prevention of Breast Cancer 117

Table 2 Case-control and cohort studies of intake of fatty foods and breast cancer in women

Relationship between foods
Study design and risk for breast cancer
(number of

Ref Location participants) Increased risk No increased risk

23 California cohort of Seventh none meat
Day Adventists poultry
(184 deaths)

24 Italy case:control dairy products meat
(368:373)

25 Alberta case:control beef eggs
(577:826) pork cheese

desserts cream
butter milk

26 France case:control cheese butter
(1010:1950) milk yogurt

27 Greece case:control none meat
(120:120) eggs

dairy products

28 California cohort of Seventh none meat
Day Adventists cheese
(142 cases in milk
20 years) eggs

29 Vancouver case:control gravy pork
(846:862) beef sausage

milk butter
cheese

30 Utah case:control food containing milk
(172:190) fiber cheese

yogurt

There has been considerable debate as to why the dietary fat and breast cancer
hypothesis that emerged from animal and correlational studies has not been sup-
ported by case-control and cohort studies [5]. There are four possible explanations:

1. The hypothesis may not be true. Human breast cancer may be a different dis-
ease from that seen in rodents, and the correlational studies may reflect an arti-
factual relationship with fat that is really due to a set of other causal factors.

2. The diet within a single population may be too homogeneous. Because the same
amount of variation in dietary fat intake seen among countries in international
correlational studies is not found among individuals within case-control or co-

Page 123

118 Tim E. Byers and David F. Williams

hort studies, the expected magnitude of risk at the extremes of the population's
distribution of fat intake may be too small to detect.

3. Mis-classification due to unreliable measurements of dietary intake of individ-
uals may bias the expected relative risk (of the order of 1.5-2.0 for the extreme
quartiles of intake) towards 1.0. Hence the dietary fat-breast cancer association
could not be detected without studying prohibitively large samples.

4. Diet many years earlier may have more effect on breast cancer risk than does
more recent diet.

It is obvious that the role of dietary fat in breast cancer risk in women needs
clarification by randomized controlled trials and the Women's Health Trial (WHT)
was conceived to determine this role [31]. The WHT was planned as a multisite in-
tervention trial. Approximately 32000 women at high risk for breast cancer were to
have been randomized into an intervention group (that would intensively reduce fat
intake to 20% of calories) or a control group (that would receive minimal dietary ad-
vice). Breast cancer incidence was then to be monitored prospectively over 10 years.

In 1988 the National Cancer Institute (NCI) decided not to fund the WHT, des-
pite successful pilot testing. NCI was uncertain about the assumptions of the size of
the expected effect of the intervention on breast cancer risk, and questioned
whether women would maintain a diet with only 20% of calories derived from fat,
over several years. Inflating the sample size to compensate for these uncertainties
made the cost of the trial prohibitive [4]. Whether another trial, perhaps combining
heart disease as an outcome, can be funded in the future is yet to be decided. An in-
dependent role for total caloric intake and energy balance has recently been postu-
lated by both animal experimenters and epidemiologists. Rats on a calorie-restricted
diet are unlikely to develop mammary cancer even when fed a diet very high in the
proportion of calories derived from fat [32]. Energy balance studies in which rats are
exercised, and also some limited epidemiologic studies, suggest that high levels of
physical activity might lower the risk of mammary cancer [32,33]. These observations
present a challenge to epidemiologists for the design [34] and interpretation [35] of
relevant studies in women.

Other Dietary Factors

Many of the studies summarized in Tables 1 and 2 investigated the role of risk fac-
tors in the diet other than fat. Findings for other dietary factors are generally as
weak and inconsistent as are those for dietary fat. This raises the possibility that
many of the relationships to risk described in various studies may be chance findings.
Some studies suggest that eating fruits and vegetables might be associated with lower
risk, but this finding has been inconsistently observed [9].

Prospective studies have been conducted in which nutrient levels in blood sam-

Page 244

244

tissue culture for testing agents 170
toremifene 163
total mastectomy (see also Mastectomy)

138,140
toxicity monitoring of agents 216, 217
transformed cells 7,170,172,175
transforming growth factor alpha 54, 175
transforming growth factor beta 54, 151,

161,175,233
transforming growth factors (see Growth

factors)
trioxifene 162
tumour doubling time 170, 172, 175
tumor heterogeneity 192
tumor initiation (see Cancer initiation)
tumorigenesis (see Carcinogenesis)
tumour differentiation (see Differentiation

mechanism)
tumour promotion (see Cancer promotion)
tumour suppressor genes 54

Index

UK women (see British women)
United States women 27-29, 88, 89, 97, 99,

106,116,120,124,125,128

viral infection in initiation 5, 6, 9
vitamin A analogues in protection 119,

164,172,234
vitamin C in protection 176
vitamin E in protection 176

weight as risk factor 114,122,123,126
weight control in protection 127
weight-for-height index 123
wet cerumen genotype 224

younger age groups, risk for 31,78,79,
81-83,89

Yugoslavian women 27-29

zinc in protection 174

Page 245

Women at High Risk to Breast Cancer

Edited by Basil A. Stoll, Honorary Consultant Physician to Oncology Department, St.
Thomas' Hospital and Joint Breast Clinic, Royal Free Hospital, London, U.K.

Health professionals who have to counsel women anxious about their risk of developing
breast cancer, urgently need an up-to-the-minute account of factors which make a woman
more susceptible to the disease. This book provides an authoritative and balanced survey
of the latest research into the genetic, familial, hormonal, reproductive, nutritional, racial
and geographic factors which are associated with an increased predisposition to breast
cancer.
The book also discusses the effectiveness of population screening for breast cancer, the
psychological problems and correct counselling, and the state of the art in genetic
counselling. In relation to prevention, some of the chapters discuss recent research which
suggests that the factors which stimulate the growth of breast cancer can be modulated by
hormones, chemical agents or elements in the diet.
The book's interdisciplinary and fully practical approach make it a valuable reference not
only for physicians and nurses but also for health educators, counsellors and other
psychosocial professionals involved in cancer care and education in the community.

Hardbound, 143 pp.
1989 KLUWER ACADEMIC PUBLISHERS ISBN 0-89838-416-8

A new monograph entitled Women at High Risk to Breast Cancer is a welcome reference
that will be particularly useful to clinicians, epidemiologists, and counselors who
concern themselves with the prevention and early detection of breast cancer ... Of special
importance is a presentation of interventions that might be used in the future to prevent
breast cancer, once developmental issues have been resolved by basic research and
feasibility demonstrations ... The reader can use this massive accumulation of references
to stimulate independent consideration of ways to advance the understanding of breast
cancer development, recognizing that this understanding will ultimately lead to breast
cancer control.

KAREN JOHNSTON
Vincent T. Lombardi Cancer Center
Georgetown University School of Medicine,
Washington, DC, U.S.A.

Review in:
J. of the National Cancer Institute,
Volume 81, No. 24, December 1989

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