An Antiestrogenic Activity Score for tamoxifen and its metabolites is associated with breast cancer outcome.

PURPOSE: Endoxifen concentrations have been associated with breast cancer recurrence in tamoxifen-treated patients. However, tamoxifen itself and other metabolites also show antiestrogenic anti-tumor activity. Therefore, the aim of this study was to develop a comprehensive Antiestrogenic Activity Score (AAS), which accounts for concentration and antiestrogenic activity of tamoxifen and three metabolites. An association between the AAS and recurrence-free survival was investigated and compared to a previously published threshold for endoxifen concentrations of 5.97 ng/mL. PATIENTS AND METHODS: The antiestrogenic activities of tamoxifen, (Z)-endoxifen, (Z)-4-hydroxytamoxifen, and N-desmethyltamoxifen were determined in a cell proliferation assay. The AAS was determined by calculating the sum of each metabolite concentration multiplied by an IC50 ratio, relative to tamoxifen. The AAS was calculated for 1370 patients with estrogen receptor alpha (ERα)-positive breast cancer. An association between AAS and recurrence was investigated using Cox regression and compared with the 5.97 ng/mL endoxifen threshold using concordance indices. RESULTS: An AAS threshold of 1798 was associated with recurrence-free survival, hazard ratio (HR) 0.67 (95% confidence interval (CI) 0.47-0.96), bias corrected after bootstrap HR 0.69 (95% CI 0.48-0.99). The concordance indices for AAS and endoxifen did not significantly differ; however, using the AAS threshold instead of endoxifen led to different dose recommendations for 5.2% of the patients. CONCLUSIONS: Endoxifen concentrations can serve as a proxy for the antiestrogenic effect of tamoxifen and metabolites. However, for the aggregate effect of tamoxifen and three metabolites, defined by an integrative algorithm, a trend towards improving treatment is seen and moreover, is significantly associated with breast cancer recurrence.

Impact of breast cancer on anti-mullerian hormone levels in young women.

Young women with breast cancer face treatments that impair ovarian function, but it is not known if malignancy itself impacts ovarian reserve. As more breast cancer patients consider future fertility, it is important to determine if ovarian reserve is impacted by cancer, prior to any therapeutic intervention. A cross-sectional study was conducted comparing if ovarian reserve, as measured by anti-mullerian hormone (AMH), follicle stimulating hormone (FSH), and inhibin B (inhB), differed between 108 women with newly diagnosed breast cancer and 99 healthy women without breast cancer. Breast cancer participants were ages 28-44 and were recruited from two clinical breast programs. Healthy women ages 30-44 without a history of infertility were recruited from gynecology clinics and the community. The median age (interquartile range) was 40.2(5.5) years for breast cancer participants and 33.0(4.6) years for healthy controls. The unadjusted geometric mean AMH levels (SD) for breast cancer participants and controls were 0.66(3.6) and 1.1(2.9) ng/mL, respectively. Adjusting for age, body mass index, gravidity, race, menstrual pattern, and smoking, mean AMH levels were not significantly different between breast cancer participants and healthy controls (0.85 vs. 0.76 ng/mL, p = 0.60). FSH and inhB levels did not differ by breast cancer status. In exploratory analysis, the association between AMH and breast cancer status differed by age (p-interaction = 0.02). AMH may be lower with breast cancer status in women older than 37. In younger women, AMH levels did not differ significantly by breast cancer status. Among the youngest of breast cancer patients, ovarian reserve as measured by AMH, FSH, and inhibin B did not differ significantly from healthy women of similar age. In older breast cancer patients, ovarian reserve may be adversely impacted by cancer status. These findings support the potential success and need for fertility preservation strategies prior to institution of cancer treatment.

Insulin Resistance Improves More in Women than In Men in Association with a Weight Loss Intervention.

BACKGROUND: Fasting glucose and homeostatic model assessment-insulin resistance (HOMA-IR) are important measures of the risk for metabolic syndrome and diabetes. Weight loss interventions are considered part of the first line of therapy for those who develop disease states associated with insulin resistance, such as pre-diabetes, diabetes, or metabolic syndrome. Sex differences in insulin resistance have been extensively reported, but sex differences in the ability to improve insulin sensitivity are not well-established. This study sought to identify factors that predict change in HOMA-IR in response to weight loss. METHODS: Non-diabetic subjects who were overweight/obese (n=100) were randomly assigned to a walnut-enriched reduced-energy diet or a standard reduced-energy-density diet in a 6-month weight loss intervention. There were no significant differences in weight change, glucose, insulin, or HOMA-IR between the two diet groups. These subjects were combined into a single cohort and analyzed with multivariate analysis. RESULTS: The combined groups lost an average of 8.7 kg (p<0.0001), decreased serum glucose by an average 0.2 mmol/L (p<0.001), and decreased HOMA-IR by an average of 1.4 (p<0.0001). Change in HOMA-IR (R2=0.69) was positively associated with weight change (p<0.0001) and male sex (p<0.01), and negatively associated with baseline HOMA-IR (p<0.0001). CONCLUSION: Findings from this study suggest that men may have a more difficult time improving insulin sensitivity as compared with women with an equivalent weight loss and baseline HOMA-IR. One hypothesis to explain the differences across sexes may be due to sex differences in visceral adipose fat (VAT). This may mean that insulin resistant men require more aggressive intervention than women to prevent progression to metabolic syndrome or diabetes.

Factors Associated with Visceral Fat Loss in Response to a Multifaceted Weight Loss Intervention.

BACKGROUND: Visceral adipose tissue is more metabolically active than other fat depots and is more closely associated with obesity-related diseases, such as cardiovascular disease and type 2 diabetes, than indicators of obesity, such as body mass index. Across various strategies to promote weight loss, including energy-reduced diet and exercise, variable effects on VAT compared to loss of total body fat have been reported. METHODS: To examine the effect of a behavioral weight loss intervention using portion-controlled prepackaged entrées on VAT, we examined data and measurements from overweight/obese men and women (N=183) who were assigned to a weight loss intervention and prescribed a reduced-energy diet with either portion-controlled prepackaged entrées or self-selected meals in a randomized clinical trial. VAT was estimated with dual-energy X-ray absorptiometry at baseline and study end (12 weeks). RESULTS: VAT loss was greater for the prepackaged entrees group (p=0.02), with an average loss of 29% compared to an average loss of 19% among participants consuming self-selected meals. VAT (mean [SEM]) was 1651 (71) g and 1546 (157) g at baseline and 1234 (59) g and 1278 (118) g at study end in the prepackaged entrees and self-selected meal groups, respectively. Greater VAT loss was associated with higher baseline weight and VAT, and greater weight loss, but not associated with age or physical activity. CONCLUSION: Prescribing portion-controlled prepackaged entrees in a behavioral weight loss intervention promotes a reduction in VAT, which should promote improved metabolic profile and reduced cardiovascular disease risk.

Low-energy reporting in women at risk for breast cancer recurrence. Women's Healthy Eating and Living Group.

This study examined the extent of low-energy reporting and its relationship with demographic and lifestyle factors in women previously treated for breast cancer. This study used data from a large multisite clinical trial testing the efficacy of a dietary intervention to reduce risk for breast cancer recurrence (Women's Healthy Eating and Living Study). Using the Schofield equation to estimate energy needs and four 24-h dietary recalls to estimate energy intakes, we identified women who reported lower than expected energy intakes using criteria developed by G. R. Goldberg et al. (Eur. J. Clin. Nutr., 45: 569-581, 1991). We examined data from 1137 women diagnosed with stage I, stage II, or stage IIIA primary, operable breast cancer. Women were 18-70 years of age at diagnosis and were enrolled in the Women's Healthy Eating and Living Study between August 19, 1995, and April 1, 1998, within 4 years after diagnosis. The Goldberg criteria classified about one-quarter (25.6%) as low-energy reporters (LERs) and 10.8% as very LERs. Women who had a body mass index >30 were almost twice (odds ratio, 1.95) as likely to be LERs. Women with a history of weight gain or weight fluctuations were one and a half times as likely (odds ratio, 1.55) to be LERs as those who were weight stable or weight losers. Age, ethnicity, alcohol intake, supplement use, and exercise level were also related to LER. Characteristics (such as body mass index, age, ethnicity, and weight history) that are associated with low-energy reporting in this group of cancer survivors are similar to those observed in other populations and might affect observed diet and breast cancer associations in epidemiological studies.

Responsiveness of carotenoids to a high vegetable diet intervention designed to prevent breast cancer recurrence.

Epidemiological studies suggest that a high vegetable diet may reduce risk for breast cancer and may also improve prognosis after the diagnosis of breast cancer. Circulating carotenoids may serve as a biomarker of vegetable and fruit intake, although several factors affect their bioavailability from food sources and may influence concentrations. One purpose of this study was to identify factors predictive of serum carotenoid, retinol, and alpha-tocopherol concentrations in 79 postsurgically resected breast cancer patients at enrollment and at 12 months in a feasibility study of a high vegetable, low fat diet intervention to reduce risk for cancer recurrence. Another purpose was to identify variables associated with change in these serum concentrations 12 months after randomization into control and intervention groups. The diet intervention (versus control) group had significantly greater increases in carotenoid intakes (P < 0.03) and significantly greater increases in serum concentrations of lutein, alpha- and beta-carotene, lycopene, and retinol (P < 0.04). Stepwise multiple regression revealed the level of dietary intake to be predictive of most serum carotenoid concentrations at baseline and 12 months, with additional associations between selected micronutrient concentrations and serum cholesterol, body mass index, age, percentage of energy intake from fat, and alcohol intake also observed at these time points. Intervention group change in serum carotenoid concentrations was inversely associated with baseline level, age, and change in serum cholesterol concentration and positively associated with change in carotenoid and alcohol intake. Circulating carotenoid concentrations are responsive to a high vegetable diet intervention, which also included reduced dietary fat and increased fiber intakes, to reduce risk for breast cancer recurrence.

Comparison of serum carotenoid responses between women consuming vegetable juice and women consuming raw or cooked vegetables.

The objective of this study was to examine serum concentrations of alpha-carotene, beta-carotene, lutein, lycopene, and beta-cryptoxanthin due to consumption of vegetable juice versus raw or cooked vegetables. Subjects included female breast cancer patients who had undergone surgical resection and who were enrolled in a feasibility study for a trial examining the influence of diet on breast cancer recurrence. A high-vegetable, low-fat diet was the focus of the intervention, and some of the subjects were specifically encouraged to consume vegetable juice. At 12 months, blood samples were collected and analyzed for carotenoid concentrations via high-performance liquid chromatography methodology. Matched analysis and paired t test were conducted on two groups: those who consumed vegetable juice (the juice group) and those who consumed raw or cooked vegetables (no juice group). Serum concentrations of alpha-carotene and lutein were significantly higher in the vegetable juice group than in the raw or cooked vegetable group (P < 0.05 and P = 0.05, respectively). Paired t test analysis did not demonstrate a significant difference in serum values of beta-carotene, lycopene, and beta-cryptoxanthin between subjects consuming juice and those not consuming any juice. These results suggest that alpha-carotene and lutein appear to be more bioavailable in the juice form than in raw or cooked vegetables. Therefore, the food form consumed may contribute to the variability in serum carotenoid response to vegetable and fruit interventions in clinical studies.

Dietary supplement use by women at risk for breast cancer recurrence. The Women's Healthy Eating and Living Study Group.

OBJECTIVE: To develop a method of collecting, organizing, and analyzing information on nutrient and nonnutrient dietary supplement use by women at risk for breast cancer recurrence as a component of nutrition assessment and monitoring, and to describe the characteristics associated with dietary supplement use in this population at enrollment in a clinical trial to prevent breast cancer recurrence. DESIGN: Cross-sectional descriptive study design. SUBJECTS: Women diagnosed with breast cancer within the previous 4 years (n=435). ANALYSIS: Dietary supplements reported in four 24-hour dietary recalls were categorized according to primary nutrient and nonnutrient contents. Prevalence of dietary supplement use is described. Associations between supplement use and demographic and participant characteristics were examined using chi(2) analysis and logistic regression. RESULTS: Dietary supplement use was reported by 80.9% of the women. Increased likelihood of supplement use was associated with demographic (eg, older age, higher level of education, white race vs other ethnic groups) and personal (eg, lower body mass index, moderate alcohol consumption) characteristics. Use of vitamin C and related compounds, other nutrients (eg, n-3 fatty acids, evening primrose oil), and herbal products was inversely associated with months since diagnosis; use of miscellaneous supplements (eg, shark cartilage) was directly associated with more advanced stage at diagnosis. APPLICATIONS: Monitoring dietary supplement use is an important aspect of nutrition assessment, especially in populations with chronic health conditions or medical diagnoses. Demographic and personal characteristics, time passed since diagnosis, and stage of cancer at diagnosis are predictive of dietary supplement use by women at risk for breast cancer recurrence. Associations in this population may be present in other groups that are the object of nutrition intervention efforts.

Factors associated with weight gain in women after diagnosis of breast cancer. Women's Healthy Eating and Living Study Group.

OBJECTIVE: To identify the factors associated with weight gain after diagnosis of breast cancer in a heterogeneous population of women. DESIGN: Descriptive cross-sectional study. SUBJECTS: 1,116 patients who had been diagnosed with stage I, stage II, or stage IIIA primary, operable breast cancer within the previous 4 years. Patients were recruited during enrollment into a diet intervention trial to reduce risk for breast cancer recurrence. Analysis Demographic data, weight history, and physical activity information obtained by questionnaire and medical information obtained by chart review; dietary assessment based on four 24-hour dietary recalls collected by telephone. Associations between weight change after the diagnosis of breast cancer and prediction variables were examined using univariate and multiple linear regression analyses. RESULTS: Overall, 60% of the subjects reported weight gain, 26% reported weight loss, and 14% reported no change in weight after the diagnosis of breast cancer. The overall mean weight change was a gain of 2.7 kg (6 lb). Factors positively and independently associated with weight gain were time since diagnosis of breast cancer, adjuvant chemotherapy, African-American ethnicity, current energy intake, and postmenopausal status at time of study entry. Factors inversely and independently associated with weight gain were prediagnosis body mass index, age at diagnosis, education level, and exercise index score. APPLICATIONS: Higher energy intake and lower level of physical activity are independently associated with increased risk for weight gain after the diagnosis of breast cancer. Strategies to modify these behaviors are likely to influence the long-term pattern of weight change.

Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes.

We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen and examined potential correlates of endoxifen concentration levels in serum including cytochrome P450 2D6 (CYP2D6) metabolizer phenotype and body mass index (BMI). Concentration levels of tamoxifen, endoxifen, 4-hydroxytamoxifen (4OH-tamoxifen), and N-desmethyltamoxifen (ND-tamoxifen) were measured from samples taken from 1,370 patients with estrogen receptor (ER)-positive breast cancer who were participating in the Women's Healthy Eating and Living (WHEL) Study. We tested these concentration levels for possible associations with breast cancer outcomes and found that breast cancer outcomes were not associated with the concentration levels of tamoxifen, 4-hydroxytamoxifen, and ND-tamoxifen. For endoxifen, a threshold was identified, with women in the upper four quintiles of endoxifen concentration appearing to have a 26% lower recurrence rate than women in the bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55-1.00)). The predictors of this higher-risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and lower tamoxifen concentrations as compared with the mean for the cohort as a whole. This study suggests that there is a minimal concentration threshold above which endoxifen is effective against the recurrence of breast cancer and that ~80% of tamoxifen takers attain this threshold.

Food avoidance by women at risk for recurrence of breast cancer.

BACKGROUND: This cross-sectional study examined self-reported restriction of foods by middle-aged and older women at risk for breast cancer recurrence, who were participating in an intervention study, and by women without breast cancer. METHODS: Data examined were height, weight, dietary intake, and avoidance of specific food types in women with breast cancer (n = 56) and a comparison group of women without breast cancer (n = 51). Data were analyzed with t-tests and chi-square analysis. RESULTS: The broad food categories of meat, dairy foods, and sweets were restricted by women both with (53%, 74%, and 62%, respectively) and without breast cancer (47%, 63%, and 63%, respectively). Significantly more women with breast cancer avoided cakes, butter, and milk, compared with women without breast cancer (p < 0.05). Women in both groups attained a mean consumption of >75% of the Recommended Dietary Allowance for many nutrients; however, mean consumption for calcium was <75% of the RDA for the two groups. CONCLUSIONS: Analysis of food avoidance by women with breast cancer who participate in diet-intervention studies and by women without breast cancer may provide information about adherence to dietary guidelines and adequate nutrient consumption among these populations.

Nutrient intakes from foods and dietary supplements in women at risk for breast cancer recurrence. The Women's Healthy Eating and Living Study Group.

Dietary supplements have been suggested to have a role in cancer prevention and treatment. The purpose of this study was to describe the nutrient intakes from foods and dietary supplements in women at the time of enrollment into a clinical trial to prevent breast cancer recurrence. Subjects were within four years of diagnosis with Stage I, II, or IIIA breast cancer and had completed medical treatment (n = 435). Intakes were assessed with four 24-hour recalls over two weeks. Dietary nutrient intakes in supplement users were compared with intakes in nonusers, and supplement nutrient intakes in participants consuming diets providing < 75% were compared with those in participants consuming > or = 75% of recommended levels. Intakes of participants with diets meeting general guidelines for disease prevention were compared with intakes of those whose diets did not meet these guidelines. Dietary supplement use was reported by 352 (80.9%) of the participants, but frequency of excess intakes did not exceed 5% for all micronutrients examined. Women whose diets provided higher levels of most vitamins and minerals were more likely to obtain additional amounts of these micronutrients from dietary supplements. Participants reporting use of any supplement consumed diets providing more dietary fiber (p < 0.04) and less dietary fat (p < 0.001) than nonusers of any supplement. These results illustrate the importance of monitoring dietary supplement use in clinical trials with a focus on preventing cancer recurrence, because supplements can contribute substantially to nutrient intakes in the population under study.

Plasma carotenoids are biomarkers of long-term high vegetable intake in women with breast cancer.

We investigated predictors of change in plasma carotenoids from baseline to 3 y and examined plasma carotenoid concentrations at 1 and 3 y in response to a high vegetable diet. Participants were 56 women diagnosed with breast cancer and enrolled in a randomized feasibility study for a trial examining the effect of a diet high in vegetables and fruits on the risk of breast cancer recurrence. Independent t test analysis revealed that the intervention group had significantly higher vegetable and fruit servings and fiber at 12 mo and significantly higher vegetable servings at 36 mo compared with the control group (P < 0.05). Energy intake from fat was significantly lower in the intervention group at 12 and 36 mo. The intervention group had significantly higher consumption of beta-carotene, alpha-carotene, lutein and beta-cryptoxanthin at 12 mo (P < 0.05). beta-Carotene, alpha-carotene and lutein intakes also were significantly higher at 36 mo (P < 0.05). At 36 mo, the intervention group had significantly higher plasma concentrations of alpha-carotene and beta-carotene compared with the control group. Repeated-measures ANOVA revealed that the intervention group had significantly increased (P < 0.05 with Bonferroni correction) plasma beta-carotene, alpha-carotene, lutein and lycopene concentrations at 12 and 36 mo compared with baseline. Baseline carotenoid concentrations were significantly inversely predictive (P < 0.05) of plasma carotenoid change. In addition, change in body mass index (BMI) and plasma cholesterol concentrations were predictive of plasma carotenoid change from baseline to 3 y. Results of this study demonstrate that change in plasma carotenoid concentrations is associated with change in BMI, change in plasma cholesterol and baseline carotenoid concentrations. Plasma carotenoid response can be an indicator of long-term high vegetable intake for women at risk of breast cancer recurrence.

Bioavailability of beta-carotene is lower in raw than in processed carrots and spinach in women.

Populations at risk of vitamin A deficiency usually rely on dietary provitamin A carotenoids to meet vitamin A needs, yet bioavailability of these compounds is influenced by several factors as follows: location in the plant source, the presence of other influencing dietary components, and type and extent of processing. The purpose of this study was to examine the plasma beta-carotene response to raw vs. processed carrots and spinach. Subjects were eight healthy females aged 23-36 y who consumed approximately 9.3 mg beta-carotene daily from either raw or thermally processed and pureed vegetables in two 4-wk treatment periods in a crossover study. Plasma concentrations of total, all-trans-, and cis-beta-carotene and alpha-carotene were measured at base line and the end of each treatment period by using HPLC assays. Total and all-trans (but not cis) plasma beta-carotene concentrations were significantly greater than base-line concentrations in the processed feeding period (P < 0. 04) and tended to be greater in the raw feeding period (P = 0.08). Daily consumption of processed carrots and spinach over a 4-wk period produced an increase in plasma beta-carotene concentration that averaged three times that associated with consumption of the same amount of beta-carotene from these vegetables in the raw form (P = 0.09). Increased cis isomers provided in the processed vegetables did not result in significantly greater plasma cis-beta-carotene isomer concentrations. These results suggest that isomerization of beta-carotene by heat treatment does not negate the enhanced beta-carotene uptake associated with consuming commercially processed vegetables compared with raw vegetables.

Feasibility of a randomized trial of a high-vegetable diet to prevent breast cancer recurrence.

Epidemiologic evidence supports the concept that diet influences risk for breast cancer and suggests that prognosis after the diagnosis of breast cancer may also be related to modifiable nutritional factors. The purpose of this study was to investigate the feasibility of a randomized trial of a high-vegetable, reduced-fat, and increased-fiber diet intervention to reduce risk for recurrence among breast cancer survivors. This major change in dietary pattern was promoted through intensive telephone counseling. Participants were 93 women who had been diagnosed with breast cancer (stages I, II, and IIIA) within the previous four years and who had completed their initial treatment. We assessed adherence to the study diet using repeated 24-hour dietary recalls at 6 and 12 months and measurement of circulating carotenoid concentrations. Six months after randomization, the intervention group had significantly increased their mean intake of vegetables (+4.6 servings/day), fruit (+0.7 servings/day), and fiber (+6.4 g/1,000 kcal) and significantly reduced their intake of dietary fat (-9.9% of energy) compared with the control group. Circulating concentrations of carotenoids also increased in the intervention group. These changes persisted at the 12-month visit. Results of this study demonstrate that telephone counseling can be a useful approach in diet intervention and that breast cancer survivors can adopt and maintain a high-vegetable, reduced-fat dietary pattern.

Eating pathology and obesity in women at risk for breast cancer recurrence.

OBJECTIVE: This cross-sectional study investigated the relationship among obesity, depressive symptoms, eating attitudes and behaviors, and dietary intake. It compared women at risk for recurrence of breast cancer and women who had not been diagnosed with breast cancer and were recruited from the same community and age group (middle-aged and older). METHOD: Body mass index (BMI), dietary intake, self-reported depressive symptoms, and eating disorder psychopathology (assessed with the Eating Disorder Examination - Questionnaire [EDE-Q]) were examined in women who had been diagnosed with breast cancer (n = 56) and the comparison group of women with no breast cancer history (n = 52). Multivariate regression analysis was used to identify factors independently associated with global and subscale EDE-Q scores and BMI. RESULTS: BMI and depressive symptoms were significantly and independently associated with global and subscale EDE-Q scores in women at risk for breast cancer recurrence and women with no breast cancer history. Dietary restriction was also significantly associated with EDE-Q scores in the group with no breast cancer history. CONCLUSIONS: An association among obesity, depressive symptomatology, and abnormal eating attitudes and behavior may affect response to standard nutritional interventions in women at risk for breast cancer recurrence.

Correlates of obesity in postmenopausal women with breast cancer: comparison of genetic, demographic, disease-related, life history and dietary factors.

BACKGROUND: Obesity in women has been associated with a variety of factors, including genetic predisposition, social class, early age at menarche, exercise, alcohol consumption and diet. Obesity is a risk factor for the occurrence and the recurrence of breast cancer in postmenopausal women, perhaps because of increased exposure to estrogen, insulin and insulin-like growth factors (IGFs). The progesterone receptor (PR) and the steroid hormone receptor coactivator pCIP/ACTR/AIB1/TRAM1/RAC3 (AIB1) are hypothesized to mediate signaling crosstalk between these hormonal pathways. Polymorphisms in both genes have been described and their association with breast cancer risk reported. If genetic factors contribute to obesity, and the PR and AIB1 genes influence estrogenic, insulin and IGF pathways, then genetic patterns resulting from PR and AIB1 polymorphisms may be associated with obesity in postmenopausal women. OBJECTIVE: We compared the PR and AIB1 genotypes of postmenopausal women with breast cancer with demographic, disease-related, reproductive, lifestyle and dietary variables in terms of the strength of their relationship with obesity (BMI> or =30 kg/m2). SUBJECTS: A total of 301 postmenopausal women previously diagnosed with Stage I, II or IIIA breast cancer, who are enrolled in the Women's Healthy Eating and Living (WHEL) study (age: 34.5-70.8 y, BMI: 17.8-54.6 kg/m2). MEASUREMENTS: The PR polymorphism PROGINS was identified by PCR. The length of the AIB1 polyglutamine repeat was determined by PCR and nondenaturing gel electrophoresis or DNA sequencing. BMI was obtained at the baseline clinic visit upon entry into the WHEL study. Information about date of diagnosis, stage of disease, tumor hormone receptor status and adjuvant treatment received were obtained from medical records. Reproductive, menstrual history, demographic, family history of cancer, smoking history and exercise frequency and intensity information were obtained from questionnaires. Dietary and alcohol intake data came from four 24-h telephone recalls of food intake obtained at the study entry. RESULTS: The combined inheritance of PROGINS A1/A1 and AIB1 28/29, 28/30, 28/31, 29/29 or 29/30 (AIB1 LG) genotypes (adjusted odds ratio (OR)=2.22 (95% confidence interval 1.25-3.93)) and early age at menarche (<12 y) (adjusted OR=2.34 (1.12-4.86)) were each associated with the risk for obesity. Current use of tamoxifen (adjusted OR=0.49 (0.28-0.87)) and an alcohol intake > or =10 g/day (adjusted OR=0.28 (0.11-0.77)) were inversely associated with BMI > or =30 kg/m2. CONCLUSION: Early age at menarche and a PROGINS A1/A1+AIB1 LG genetic pattern had comparable levels of association with obesity in this cross-sectional sample of postmenopausal women with breast cancer. Since this was a cross-sectional rather than a case-control design, the association between PROGINS and AIB1 genotype and obesity found in this sample should be considered preliminary, and must be re-evaluated with a new and larger sample.

Reduction in fat intake is not associated with weight loss in most women after breast cancer diagnosis: evidence from a randomized controlled trial.

BACKGROUND: A reduction in dietary fat intake has been suggested as a method to promote weight loss in women at risk for breast cancer recurrence. METHODS: Weight change in response to diet intervention was examined in 1010 women who had completed treatment for Stage I, Stage II, or Stage IIIA (American Joint Committee on Cancer staging system) primary operable breast cancer during their first year of participation in a randomized, controlled, diet intervention trial to reduce risk of recurrence. Diet intervention was performed by telephone counseling and promoted a low fat diet that also was high in fiber, vegetables, and fruit. The comparison group was provided with general dietary guidelines to reduce disease risk. Multiple linear regression models were used to examine the relations among demographic and personal characteristics, changes in diet composition and exercise level, and change in body weight or body mass index. RESULTS: The average weight change in the 1-year period was 0.04 kg for the intervention group and 0.46 kg for the comparison group. For the total group, body weight was stable (+/- 5% baseline weight) for 743 women (74%), whereas 114 (11%) lost weight, and 153 (15%) gained weight. These distributions were similar in the two study groups inclusive of all study participants and for only those women with a baseline body mass index of > or = 25 kg/m2. Initial body mass index and changes in fiber and vegetable intakes, but not change in percent of energy obtained from fat, were associated independently with change in weight or body mass index. CONCLUSIONS: For most women at risk for breast cancer recurrence, diet intervention to promote a reduction in fat intake was not associated with significant weight loss. Testing the effect of a substantial change in diet composition on risk for breast cancer recurrence is unlikely to be confounded by weight loss in subjects who were the recipients of intensive intervention efforts.