Women's Intervention Nutrition Study Research Articles

Lifestyle factors and survival in women with breast cancer.

With increasing longevity and more effective cancer therapies, the population of cancer survivors is increasing. For example, it is estimated that there are over 2 million breast cancer survivors in the United States. Among cancer survivors and their families, there is substantial interest in whether there is anything that they can do beyond conventional therapy to improve their prognosis. Chief among these is interest in diet and use of complementary and alternative therapies. Despite this interest, there is surprisingly little that is known about the effects of these factors on cancer survival. This is in part because of the usual approach to research on diet and breast cancer in human populations. Studies that have had food and nutrition as a main interest have focused almost exclusively on cancer etiology and prevention; there are literally hundreds of such studies. Meanwhile, studies of populations after a breast cancer diagnosis have rarely considered lifestyle factors. Such studies have focused largely on therapeutics, such as effects of different chemotherapy regimens, or prognostic factors, such as the effects of stage of disease, hormone receptor status, or gene expression signatures on prognosis. To the extent that lifestyle factors have been a focus of cancer prognosis studies, they have often been aimed at the question of whether they impact quality of life, and not on whether they influence cancer survival or recurrence. There have been a handful of studies that have had lifestyle factors such as diet and physical activity as a principal focus. In addition to 2 randomized trials, the Women's Intervention Nutrition Study (WINS) and the Women's Healthy Eating and Living Study, there are at least 5 ongoing prospective cohort studies in breast cancer survivors that have diet as a main focus. Although these studies differ in various aspects, they are all aimed at examining whether differences in diet may result in differences in recurrence and mortality rates. One such study, the Pathways Study, is a prospective cohort study that began recruitment of study participants in early 2006. This study is unique in that it is enrolling women as soon after breast cancer diagnosis as is practical, whereas other studies have generally enrolled women after completion of adjuvant therapy or later. This and other studies promise to provide some of the first objective information regarding diet and breast cancer prognosis and serve as models for studies of diet and prognosis of other cancers.

Dietary Fat and Breast Cancer: Contributions From a Survival Trial

EDITORIALS 1753 The relation between dietary fat and breast cancer incidence and survival remains one of the most controversial hypotheses in nutritional epidemiology, with mostly observational studies showing rather inconsistent results ( 1 – 3 ) . In this ongoing debate, results of a pertinent intervention trial are potentially highly informative. In this issue of the Journal, Chlebowski et al. ( 4 ) report interim results of the Women’s Intervention Nutrition Study (WINS), a low-fat dietary intervention trial among women diagnosed with breast cancer. The WINS fi ndings, however, raise several concerns that complicate drawing etiologic conclusions about dietary fat and breast cancer as well as making defi nitive recommendations for survivors. Results of the interim analysis ( 4 ) suggest a benefi t of dietary fat reduction on relapse-free survival: the log-rank test was of borderline statistical signifi cance ( P = .07), and exploratory multivariable Cox regression analysis showed a statistically signifi cant decrease in the risk of relapse in the group assigned to the low-fat dietary eating plan ( P = .03). A key concern is whether the improved survival could have been confounded by the higher frequency of mastectomy in the intervention group than in the control group, given that a recent pooled analysis ( 5 ) showed that breast-conserving therapy was associated with a greater risk of locoregional recurrence than mastectomy. The authors note that adjustment for the surgical procedure did not eliminate the outcome advantage observed in women randomly assigned to the low-fat dietary eating plan. Moreover, among WINS patients who underwent lumpectomy, those in the intervention group also experienced lower ipsilateral breast recurrence (11 events out of 624, compared with 31 out of 1018 in the control group) [tables 2 and 4, ( 4 ) ]. A post hoc covariate adjustment, however, is not as inferentially strong as an analysis that is based on baseline equivalence across the two groups. The treatment imbalance thus lends

Dietary Fat Reduction and Breast Cancer Outcome: Interim Efficacy Results From the Women's Intervention Nutrition Study

Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management. A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided. Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 [95% confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7], respectively; P<.001), corresponding to a statistically significant (P = .005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status. A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment.

Dietary fat reduction in postmenopausal women with primary breast cancer: Phase III Women’s Intervention Nutrition Study (WINS)

10 Background: Despite preclinical and observational studies suggesting benefit, dietary fat influence on breast cancer outcomes has been controversial. Methods: We conducted a randomized trial to test whether an intensive dietary intervention designed to reduce dietary fat intake was effective in influencing relapse-free survival in postmenopausal women with primary breast cancer. A total of 2,437 women with early stage resected breast cancer, 48–79 years old, were randomized within 365 days from surgery in a 40:60 ratio to dietary intervention or control groups at 37 U.S. sites. All received standard breast cancer management: mastectomy or lumpectomy plus radiation; tamoxifen for ER positive, protocol-defined chemotherapy for ER negative and optional chemotherapy for ER positive cases. The dietary intervention included eight bi-weekly individual counseling sessions conducted by centrally trained nutritionists who provided ongoing contacts throughout. Results: Patient characteristics and recurrence risk factors were balanced. Dietary fat intake reduction was greater in the dietary group (fat gram intake/day at 12 months, 33.3 ± 16.7, mean ± standard deviation (SD) versus 51.3 ± 24.4 in controls, respectively, p<0.001). After 60 months median follow-up, the 277 reported relapse events are outlined below by treatment group and receptor status. Conclusion: Life-style intervention resulting in dietary fat intake reduction may improve the relapse-free survival of postmenopausal breast cancer patients. No significant financial relationships to disclose.

Dietary Fat Reduction Improves Relapse-Free Survival in Postmenopausal Women Previously Treated for Early-Stage Breast Cancer: Results from a Phase III Women's Intervention Nutrition Study

pausal status, and therefore the association of fat intake with breast cancer risk may be different in postmenopausal women compared with premenopausal women. • Moreover, dietary patterns in early life have been implicated in the etiology of breast cancer, and dietary fat consumption during adolescence or even in childhood may influence the risk of breast cancer in adulthood.8 As rapid growth and maturation of the breasts occur during adolescence, a woman’s diet as an adolescent could potentially affect her risk of developing breast cancer more than her diet would as an adult.8,9 Although case-controlled studies generally do not support an association between childhood diet and risk of breast cancer,10,11 most studies suffer

Dietary patterns in women treated for breast cancer who successfully reduce fat intake: The Women’s Intervention Nutrition Study (WINS)

Objective The objectives of this study were to assess the types of dietary changes made by women who successfully reduced their fat intake in response to low-fat diet instruction and to evaluate the effects of these changes on nutrient intake. Design Two hundred women enrolled in the low-fat intervention arm of the Women’s Intervention Nutrition Study (WINS) were randomly selected. Woman whose baseline fat intake was less than 20% energy from fat were excluded from the study, resulting in a total population of 163. These women were categorized into either the strictly adherent (SA) (those who met their fat gram goal and reported less than 20 % calories from fat, n=50) or the not strictly adherent (NSA) (those who exceeded their fat gram goal and reported 20% or greater calories from fat, n=113) group. The food choices made by SA and NSA subjects were analyzed to identify those that promoted greater adherence. Subjects/setting The participants were free-living women who had been instructed to follow a diet that would meet a specific fat gram goal calculated to provide 15% of calories from fat. Statistical analyses performed Descriptive statistics were used to describe food groups and subgroups. t tests were used to determine statistical significance between and within groups. χ 2 analysis was used to assess differences in demographic variables. Results There were no marked differences in food patterns of the SA and NSA subjects when compared with the Food Guide Pyramid (FGP) recommendations. Both met FGP serving recommendations at baseline. At 12 months, both showed reductions in the number of servings from fats and oils; SA subjects showed a greater reduction (from 4.18±3.6 to 3.0±2.4) as well as a reduction in servings from the bread group intake (5.7±2.2 to 4.8±2.1). Evaluation of food subgroups from within FGP groups showed strategies that promoted fat reduction, such as reducing portion sizes of high-fat foods. The use of these strategies was greater in the SA subjects. The reduction in fat intake had little impact on nutrient adequacy. SA and NSA subjects reduced energy intake from baseline to follow-up, with SA subjects reporting lower intakes. There were few differences in nutrient intakes between the SA and NSA subjects at either time period. Conclusions The results from this study suggest specific strategies that promote successful reduction in fat intake without compromising nutrient intake. This information can be used to guide others in making dietary changes.

Setting goals and empowering lifestyle modification

There are many attributes and characteristics that are important to obtaining success in a dietary change program, whether it is for participants in a research study, a group of new moms in WIC (the Special Supplemental Nutrition Program for Women, Infants, and Children), or patients getting ready to go home after a coronary artery bypass graft. It is important to distinguish which characteristics promote the best control along with assuring that, through dietary adherence to a specific program, overall nutrition quality is maintained. Winters and associates showed that strict adherence to a reduced fat program in the Women’s Intervention Nutrition Study (WINS) was obtained by following the five principles of the WINS Low-Fat Eating Plan while still maintaining nutrition integrity ( 1 Winters B.L. Mitchell D.C. Smiciklas-Wright H. Grosvenor M.B. Liu W. Blackburn G.L. Dietary patterns in women treated for breast cancer who successfully reduce fat intake The Women’s Intervention Nutrition Study (WINS). J Am Diet Assoc. 2004; 104: 551-559 Google Scholar ).

Diet and breast cancer: can dietary factors influence survival?

Breast cancer accounts for over one third of invasive cancers in women. Earlier detection and improved initial treatments have resulted in an increasing number of women who have completed standard treatments but who remain at risk for breast cancer recurrence or early death. Epidemiological studies have linked diet composition with prognosis, and many women attempt to modify their diets and improve nutritional status following diagnosis The hypothesis that dietary factors may reduce risk for secondary cancer events and increase survival in this population is currently under study in two large randomized clinical trials: the Women's Intervention Nutrition Study (WINS) and the Women's Healthy Eating and Living (WHEL) Study. The WHEL Study is testing the effect of a diet high in vegetables, fruit, and fiber, and low in fat, on disease-free survival in women with early stage breast cancer. Hypothesized mechanisms include effects of diet modification on gonadal hormones, retinoid-like activities of carotenoids, and other protective effects of biologically active dietary constituents.

Designing a Quality Assurance System for Dietary Data in a Multicenter Clinical Trial: Women's Intervention Nutrition Study

Reliable dietary intake data are essential for determining outcomes in nutrition-related clinical trials. Nevertheless, systems for quality assurance of dietary intake data are often slighted in the design of such trials and not incorporated or monitored as the trials continue. The Women's Intervention Nutrition Study (WINS), a multicenter clinical trial investigating the effect of reduction of dietary fat intake together with adjuvant systemic therapy on recurrence rates in and survival of postmenopausal women with early stage, surgically treated, breast cancer, has developed a quality assurance system to minimize errors and to produce data that are complete and reliable. The system involves development of standardized procedures for data collection, a quality control program to evaluate the data collected, and continual monitoring and reevaluation. The WINS system is offered as a model for studies collecting dietary intake data, no matter how simple or complex the trial design. J Am Diet Assoc. 2000; 100:1186-1190.

Centralized Retention Strategies in the Multi-Center Women's Intervention Nutrition Study (WINS)

High attrition rates in large-scale clinical trials can ultimately result in decreased statistical power. WINS is a randomized trial with a recruitment goal of 2,500 women, evaluating the influence of dietary fat intake reduction on breast cancer recurrence, conducted at 38 clinical sites. To date, WINS has enrolled 1735 participants, with a 7.7% “inactive” rate (56% low-fat intervention group, 44% control group). Reasons for attrition include: unable to contact/not interested (23.8%), other medical/family problems (16.4%), caring for sick relative (9.7%), cancer recurrence (8.9%) (participants with a recurrence are encouraged to remain in the trial), too busy (7.5%), and wanted to be in the intervention group (7.5%). In response to an identified need to implement behaviorally oriented retention strategies study-wide, local and centralized procedures were developed by the WINS Intervention Unit (IU). Working with all clinical sites, the IU facilitates ongoing communication and development of local action plans for retention problems. In addition, the IU identifies “inactive” participants refractory to local clinic strategies, collects background information on such participants from clinical site Nutritionists, and via telephone, implements retention strategies by a behaviorally trained Nutrition Intervention Coordinator (NIC). During this contact, the NIC discusses participant's concerns and attempts to negotiate a compromise resulting in study continuation, such as taking “time-off” from the study or participation in a modified capacity. Following recent implementation, approximately 2-4 participants/month have been identified as candidates for this intervention. Data collection procedures are in place to evaluate effectiveness. A centralized IU can be used to develop local retention action plans and deliver behaviorally oriented telephone interventions in a large-scale clinical trial. The effectiveness of this approach is currently under evaluation.

Strategies to Maintain Long Term Adherence to a Very Low Fat Diet in a Large Scale Clinical Trial: The Women's Intervention Nutrition Study (WINS)

The potential health benefits of very low fat diets are currently under investigation in several large trials. Long term adherence to the dietary intervention is critical to answering the research question. The purpose of this study is to summarize reported barriers to adherence to a 15% kcal fat diet, and to describe successful strategies designed to address these barriers. The Women's Intervention Nutrition Study (WINS) is a long term (5+years), multi-center, randomized trial investigating the relationship between a 15%kcal fat diet and breast cancer recurrence in postmenopausal women with early stage breast cancer. Eligible women are randomly assigned to: Non-intervention Group who maintain usual diet; or Intensive Intervention Group (EG), counseled to 15% kcal fat. At each visit, participants are queried about obstacles to adherence to the low fat diet. In response to the reported barriers, WINS Intervention Unit developed several intervention strategies including: 1) individualized counseling that incorporates goal assessment, tailored messages based on stages of change, self monitoring, participant educational material (individualized modules addressing specific barriers), relapse prevention, and cognitive restructuring; 2) interactive monthly group meetings at each site and; 3) adherence monitoring of each site by the WINS National Intervention Unit. Data shows the success of these strategies with a reduction in the frequency of reported barriers: (4 vs 12 month data): “Eats Out” (27.9% vs 9.5%), ‘Too Busy” (13.4% vs 4.4%), “No Control/Cravings” (13.2% vs 4.7%), “Depression” (9.7% vs 3.8%), “Don’t Understand” (7.5% vs 0), and “No Support” ( 5.0% vs 2.2%). Comprehensive strategies to address barriers to adherence reduce participant burden, contributing to long term retention and adherence of participants.

Food Pattern Changes in Women Participating in the Women's Intervention Nutrition Study (WINS)

The potential impact of fat lowering recommendations on food choices and dietary adequacy has been of interest, particularly in special populations. WINS was designed to assess the efficacy of reducing fat intake to 15% kcal on recurrence of breast cancer. Women are randomly assigned to a non-intervention group (NIG) or a low-fat intensive intervention group (IIG). Dietary intake data is collected by three 24-hour telephone recalls at baseline and annually using the University of Minnesota's NDS. Results show that baseline fat intake of all participants is 27% kcal. Fat intake remains at the baseline level in the NIG at 12 mos. but decreases significantly in the EG to 17.5% (median values). Information on nutrient intake is not sufficient to assess food choices in this free-living population exposed to a vast variety of low-fat items. To determine food choices we conducted food pattern analysis on data from a randomly selected subset of women (n=200 from each group). Both groups met Food Guide Pyramid recommendations at baseline and at 12 mos. The only significant difference in main food group intake by 12 mos. was a reduction in fats, oils, and sweets in the HG, (p < 0.0001). This reduction was accompanied by changes in the number of HG users in subcategories of main food groups. Subcategory analysis comparing the HG to the NIG shows the IIG reduced fat grams per serving (⇓>1.5 gm/serving) in the sweets, pastries and desserts; snack foods; cheese; nuts and seeds and fats and oils subcategories. In summary, women in the HG made appropriate food choices to meet goals while those in the NIG maintained baseline food choices. These data strongly suggest that although there are a variety of low-fat food choices available in the market place, an intensive intervention protocol such as the WINS Low-fat Eating Plan results in the selection of foods that are lower in fat when compared to a non-instructed group.

Early Stage Breast Cancer Participants can Make Significant Reductions in Dietary Fat Intake: Evidence From The Women's Intervention Nutrition Study (Wins)

LEARNING OUTCOME: To comprehend the logistics and success of nutrition intervention in a large, multi-centered clinical trial. WINS is a NCI sponsored multi-center randomized trial testing the hypothesis that dietary fat intake reduction as a component of standard adjuvant breast cancer therapy (tamoxifen + defined Chemo Rx) will reduce recurrence and increase survival for women with localized breast cancer. Currently over 1,000 women of a target of 2,500 (≥48 to ≤ 78 years), from 34 participating clinics have been randomized to either the intervention group (IIG) (target of 15% energy from fat) or the non-intervention group (NIG). The intervention is initially provided in a series of eight one on one counseling sessions with a Registered Dietitian over a four month period. Social and behavioral theories are incorporated to promote dietary change and long-term adherence through individualized intervention and goal setting. IIG counseling also includes individual “booster” visits every 3 months and monthly group nutrition and support sessions. Dietary data is collected annually via unannounced 24-hour telephone recalls using the Nutrition Data System. Data from the interim analysis (n=293) shows significant dietary change is achieved hi the IIG from baseline to 12 months [% energy from fat (25.9% to 17.2%, median)] with no significant change in NIG participants. This represents a total reduction of fat intake of 39.1% in the IIG. WINS has designed a successful intervention for reducing dietary fat intake in a one on one and group counseling format, thus allowing for definitive evaluation of the effect of dietary fat intake reduction on breast cancer outcome.

The Challenges of Assessing Fat Intake in Cancer Research Investigations

Ecological comparison of the incidence of cancer (eg, large-scale differences between countries in the incidence of breast, prostate, and colon cancer) can be explained best by substantial differences in the intake of dietary fat. Additionally, there is a vast amount of animal and mechanistic data that strongly supports the hypothesis that dietary fat, independent of caloric intake, appears to have a major effect on the incidence and mortality rates for cancer. Yet, results from human case and cohort studies are inconsistent in linking carcinogenesis with fat intake. This is due to several factors. Reported intakes may not reflect previous long-term intakes and may be con-founded by several sources of error, including memory and estimates of portion size. Additionally, ongoing media reports of adverse health effects from high-fat diets may impart a social desirability bias to self-reporting of fat intake. These factors may be significant when investigating the relationship between dietary intake and cancer. Studies have shown considerable error in self-reported dietary data, with under-estimations in energy intake ranging from 3% to 18%. Such a wide range likely is due to differences in dietary assessment methodologies, which highlights the need to continue to develop improved techniques of data collection to relate nutrition better to health outcomes. The Women's Intervention Nutrition Study (WINS) is investigating the effect, of dietary fat on the incidence of recurrence and survival in women with early-stage breast cancer. WINS is employing the multiple-pass 24-hour telephone recall system along with enhanced quality control measures to assess dietary intake. This dietary assessment method is particularly applicable when comparing two populations when one population is treated by an extensive dietary intervention. J Am Diet Assoc. 1997; 97(supll):S5-S8.

Fat, Caloric Intake, and Obesity: Lifestyle Risk Factors for Breast Cancer

Dietary fat is a likely important determinant of postmenopausal breast cancer as part of an intricate and inseparable interaction of lifestyle cancer risk factors that include dietary fat, type of fat, energy intake and expenditure, and obesity. These factors possibly build upon individual susceptibilities derived from a complex array of polygenetic risk determinants. Epidemiologic studies have not provided conclusive evidence for a dietary fat-breast cancer association, partly because studies that focus on a single nutrient cannot always evaluate readily the interactive effects of other lifestyle factors. Further, persons generally underestimate their usual dietary intake, measured by either food frequency questionnaires (FFQs) or diet records. A dietary measurement model that accounts for this underreporting demonstrated that FFQs and diet records may not be able to detect a dietary fat-breast cancer association because of measurement error biases. Although meta-analysis of epidemiologic data across individual studies suggests only a weak association between breast cancer and dietary fat, this result is compatible with the dietary measurement model and does not rule out a contributing role for dietary fat, either alone or with other causative factors. Research is needed that focuses on a comprehensive approach to dietary lifestyle choices and breast cancer risk and that emphasizes a fat-caloric intake-obesity linkage. The best hope for a definitive answer may rest with randomized, controlled clinical trials. Two such trials, the Women's Health Initiative and the Women's Intervention Nutrition Study, are under way. J Am Diet Assoc. 1997;97(suppl):S24-S30.

Cancer prevention

Cancer prevention

Nutritional aspects of breast cancer.

Nutrition, in its broadest sense, plays a clear role in breast cancer, identified through its relationship to such known risk factors as rate of growth and development, age at menarche, adult height, postmenopausal body weight, and fat distribution. The relative importance of daily diet is hotly debated. There is no agreement on the relative importance of nutrition's effect, the responsible food groups and nutrients, nor the age or ages at which it can be influential. Evidence linking breast cancer and diet comes from human ecologic and observational studies as well as a body of experimental feeding studies in rats and mice. The population studies, including increasing numbers of migrant studies, and the animal experiments suggest that high-fat diets promote breast cancer, particularly among older women. Studies that compare diets of persons with and without breast cancer and those that record breast cancer incidence among women with different dietary histories have been inconclusive enough as to warrant randomized intervention trials. Recognition of differences between the risk factors for premenopausal and postmenopausal women and increasing insight into the ages at which known risk factors exert their influence have helped in the design of these trials. Human feeding studies and the trials themselves are identifying metabolic changes and their biomarkers as well as biomarkers for changes in fat and nutrient intakes. The Women's Health Initiative Dietary Modification Trial was designed to show whether a sustained (9-year) low-fat, high-fruit-and-vegetable eating pattern will lower the incidence of breast cancer among women who will be between ages 59 and 88 when the trial ends, the time of peak incidence. Meanwhile, the Women's Intervention Nutrition Study will learn in approximately 5 years whether a low-fat, adjuvant eating pattern will improve the prognoses of postmenopausal women with early and moderate stage breast cancer and whether tamoxifen should be used as at least part of their treatment. The results of these trials will have important applications for both public health and the provision of medical care.

The scope of nutrition intervention trials with cancer-related endpoints

The National Cancer Institute currently is supporting three full-scale dietary modification trials with cancer-related endpoints. These studies are the dietary component of the Women's Health Initiative, designed to determine whether a low-fat diet will reduce the incidence of breast and colorectal cancer and/or coronary heart disease; the Women's Intervention Nutrition Study, designed to test whether a dietary fat reduction program will decrease breast cancer recurrence and increase patient survival; and the Polyp Prevention Trial, designed to determine whether a low-fat, high-fiber diet will reduce the recurrence of adenomatous polyps. Design issues associated with these full-scale dietary modification outcome trials have been addressed successfully in a series of feasibility studies. The ability to achieve a sustained reduction of 50% in dietary fat intake with maintenance of nutritional adequacy has been demonstrated in randomized trials of postmenopausal populations with resected breast cancer and in populations at increased risk for breast cancer. In these studies comparing dietary fat reduction programs with control lifestyles, a series of associated biologic changes, consistent with the self-reported dietary alterations, have been observed. These changes include body weight reduction, serum and/or plasma estradiol concentration reduction, fasting plasma cholesterol concentration reduction, and alteration in free fatty acid levels. Such results provide a substantial basis for reliably estimating the level of adherence that can be anticipated in trials of dietary change, a prerequisite for appropriate calculation of the sample size needed for multicenter, full-scale outcome studies. As a result, the efficacy of a series of dietary alterations (including fat reduction, fiber addition, and/or increased fruit and vegetable intake) on cancer-related endpoints with potential major public health significance (breast cancer recurrence, breast cancer development, and colonic polyp recurrence) now are being addressed definitively in prospective clinical trials.

Epidemiology and Natural History of Breast Cancer: Implications for the Body Weight–Breast Cancer Controversy

The mechanisms of differentiation of the mammary gland apparently can explain the contradictory findings on the association of breast cancer with excess body weight. Excess weight may be related to the initiation of breast cancer in premenopausal women through its effect on menstrual cycles and on progesterone secretion and to the promotion of breast cancer in postmenopausal women through its effect on estrogen metabolism. Although body weight is unlikely to be as strong a risk factor for breast cancer as it is for endometrial cancer, it may have a greater importance from a public health point of view, because the ratio of the incidence of breast cancer to that of endometrial cancer is 4.5 in whites and 6 in blacks. Thus, more studies seem warranted. It is not possible, however, to rule out the view that the reported correlation between excess weight and breast cancer is attributable to failure to adjust for potential confounders, such as dietary fat. New insights may come from the combined assessment of weight, different types of dietary fat, and reproductive history factors known to be involved in the natural history of breast cancer. For example, in the Women's Intervention Nutrition Study (WINS), the survival rate of breast cancer patients on a 20 per cent fat diet is being compared with that of breast cancer patients of similar weight keeping their usual 35 to 40 per cent fat diet. This investigation will show whether dietary fat influences the rate of progression (metastasis) and of promotion (occurrence of cancer in the other breast) independent of body weight.