Low circulating concentrations of vitamin D metabolites have been associated with increased risk for several diseases and clinical conditions. Large observational studies and surveys have shown that obesity is independently associated with lower serum 25-hydroxyvitamin D (25(OH)D) concentration. Few studies have examined the effect of weight loss on serum 25(OH)D concentration. The purpose of this study was to prospectively examine the effect of weight loss on serum 25(OH)D concentration. Data were collected from 383 overweight or obese women who participated in a 2-year clinical trial of a weight-loss program, in which 51% (N = 195) lost at least 5% of baseline weight by 24 months, 18% (N = 67) lost 5–10%, and 33% (N = 128) lost >10%. Women who did not lose weight at 24 months had an increase in serum 25(OH)D of 1.9 (9.7) ng/ml (mean (SD)); 25(OH)D increased by 2.7 (9.1) ng/ml for those who lost 5–10% of baseline weight; and 25(OH)D increased by 5.0 (9.2) ng/ml for those who lost >10% of baseline weight (P = 0.014). At baseline, 51% (N = 197) of participants met or exceeded the recommended serum concentration of 20 ng/ml. By study end, 64% (N = 230) of overweight or obese women met this goal, as well as 83% (N = 20) of those whose weight loss achieved a normal BMI. These findings suggest that weight loss, presumably associated with a reduction in body fat, is associated with increased serum 25(OH)D concentration in overweight or obese women.
Obesity and components of energy imbalance, i.e., excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, “The Role of Obesity in Cancer Survival and Recurrence”; discussions included: 1) mechanisms associated with obesity and energy balance that influence cancer progression; 2) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; 3) associations between obesity and cancer risk, recurrence, and mortality; 4) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and 5) future directions.
neoplasms; obesity; diet; physical activity; survival; recurrence
To review and summarize evidence from clinical and epidemiologic studies that have examined the relationship between nutritional factors, survival, and recurrence after the diagnosis of breast cancer.
Materials and Methods
Relevant clinical and epidemiologic studies were identified through a MEDLINE search. References of identified reports also were used to identify additional published articles for critical review.
Several nutritional factors modify the progression of disease and prognosis after the diagnosis of breast cancer. Overweight or obesity is associated with poorer prognosis in the majority of the studies that have examined this relationship. Treatment-related weight gain also may influence disease-free survival, reduce quality of life, and increase risk for comorbid conditions. Five of 12 studies that examined the relationship between dietary fat and survival found an inverse association, which was not evident on energy adjustment in most of these studies. The majority of the studies that examined intakes of vegetables or nutrients provided by vegetables and fruit found an inverse relationship with survival. Alcohol intake was not associated with survival in the majority of the studies that examined this relationship.
Much remains to be learned about the role of nutritional factors in survival after the diagnosis of breast cancer. Healthy weight control with an emphasis on exercise to preserve or increase lean muscle mass and a diet that includes nutrient-rich vegetables can be recommended. Diets that have adequate vegetables, fruit, whole grains, and low-fat dairy foods and that are low in saturated fat may help to lower overall disease risk in this population.
To test effects of parent/child training designed to increase calcium intake, bone-loading physical activity (PA), and bone density.
Two-group randomized controlled trial.
Family-based intervention delivered at research center.
117 healthy children aged 10-13 years (58.1% female, 42.7% Hispanic, 40.2% White). Ninety-seven percent of participants had at least one parent graduate from high school and 37.2% had at least one parent graduate from a 4-year university.
Children and parents were randomly assigned to diet and exercise (experimental) or injury prevention (control) interventions. Children were taught in eight weekly classes how to engage in bone-loading PA and eat calcium-rich foods or avoid injuries. Parents were taught behavior management techniques to modify children’s behaviors.
Measures at baseline, three, nine and twelve months included 24-hour diet and PA recalls, and bone mineral density (BMD) by DXA.
ANOVA and Generalized Estimating Equations assessed group by time differences. Comparisons were conducted separately for boys and girls.
For boys, cross-sectional differences between experimental versus control group were achieved for 3 and 9-month calcium intake (1352 vs. 1052mg/day, 1298 vs. 970mg/day, p<0.05). For girls, marginal cross-sectional differences were achieved for high-impact PA at 12 months (p<0.10). For calcium intake, a significant group by time interaction was observed from pre to post test for the full sample (p=.008) and for girls (p=.006) but not for boys. No significant group by time differences in calcium were observed across the follow-up period. No group by time differences were observed for high impact physical activity. Among boys, longitudinal group by time differences reached significance for total hip BMD (p=.045) and femoral neck BMD (p=.033), even after adjusting for skeletal growth. Similar differential increases were observed among boys for BMC at the hip (p=.068) and total body (p=.054) regions. No significant group by time interaction effects were observed for girls at any bone site for BMD. For BMC, control girls showed a significant increase (p=.03) in spine BMC compared to intervention girls
This study demonstrated that parent/preteen training can increase calcium intake and attenuate the decline in high-impact PA. Results suggest that more powerful interventions are needed to increase activity levels and maximize bone mineral accrual during pre-adolescent years.
Calcium; diet; parent education; physical activity; preteens; Osteoporosis prevention; Manuscript format: research; Research purpose: intervention testing/ program evaluation; Study design: randomized trial; Outcome measure: behavioral, biometric; Setting: family; Health focus: fitness/physical activity, nutrition; Strategy: education, skill building/behavior change; Target population age: youth; Target population circumstances: geographic location
acculturation; diet; Asian Americans; nutrition assessment
A hypercoagulable state is a potential mechanism linking elevated blood pressure (BP), adiposity and a sedentary lifestyle to development of coronary heart disease (CHD). We examined relationships among aerobic fitness and adiposity in 76 sedentary subjects with elevated BP. Blood levels of plasminogen activator inhibitor-1 (PAI-1), D-dimer, von Willebrand factor (vWF) and thrombomodulin were assessed as biomarkers of coagulation. In individuals with elevated BP, percent body fat and fitness were associated with biomarkers indicative of a hypercoagulable state, even after demographic and metabolic factors were considered. D-dimer was positively associated with percent body fat (beta=0.37, p=0.003). PAI-1 was higher in men than in women (beta=−0.31, p=0.015) and associated with lower VO2peak (beta=−0.35, p=0.024). Thrombomodulin was positively associated with VO2peak (beta=0.56, p< 0.01). vWF was not significantly associated with fitness or adiposity. Our results emphasise that both percent body fat and physical fitness are important in the maintenance of haemostatic balance.
fitness; adiposity; coagulation; hypertension; blood pressure; D-dimer. PAI-1; von Willebrand factor; thrombomodulin
Physical health-related quality of life scores have been, inconsistently, associated with breast cancer prognosis. This analysis examined whether change in physical health scores were related to outcomes in women with a history of breast cancer.
2343 breast cancer survivors in a randomized diet trial provided self-reported assessment of physical health-related quality of life at baseline and year 1. Based on change in physical health score, participants were grouped into subpopulations of decreased physical health, no/minimal changes, and increased physical health. Cox regression analysis assessed whether change in physical health (from baseline to year 1) predicted disease-free and overall survival; hazard ratio (HR) was the measure of association.
There were 294 additional breast cancer events and 162 deaths among women followed for 7.3 years. Improvements in physical health were associated with younger age, lower BMI, being employed, not receiving tamoxifen, lower physical activity, and lower baseline physical and mental health. There was no association of change in physical health with additional breast cancer events or mortality among women diagnosed ≤ 2 years before study enrollment. However, among women who entered the study >2 years post diagnosis, the HR for increased compared to decreased physical health was 0.38 (95% CI, 0.16 to 0.85) for all-cause mortality.
These results appear to support testing an intervention to improve physical health in breast cancer patients among patients after the acute stage of treatment.
breast cancer; physical health; survival; mortality
Previous studies examining the relationship between micronutrient intakes and survival following diagnosis of breast cancer have reported mixed results. This may be partly due to considerable variance in amounts of micronutrients consumed from diet and supplements across studies.
Early stage breast cancer survivors (n=3081) completed four 24-hour dietary and supplement recalls at the baseline assessment (1995 to 2000) and were followed for a median of 9.0 years. Mean micronutrient intakes were compared to dietary reference intakes (DRI) to assess micronutrient adequacy for both users and non-users of supplements. Cox regressions were performed to assess whether intakes of selected micronutrients were associated with all-cause mortality.
412 deaths occurred between baseline and August 2009. Among these women, more supplement users had adequate micronutrient intakes than non-users for 15 out of 17 micronutrients. Less than 10% of supplement users (< 2% of non-supplement users) reported levels that exceeded the tolerable upper limit for each micronutrient except magnesium. After adjusting for age, tumor characteristics, and health status variables, micronutrient intakes were not significantly associated with all-cause mortality.
Dietary supplements may improve overall micronutrient intakes of breast cancer survivors. However, vitamin and mineral intakes were not associated with all-cause mortality.
dietary intake; supplement use; breast cancer survival
Health-related quality of life (HRQOL) has been hypothesized to predict time to additional breast cancer events and all-cause mortality in breast cancer survivors.
Women with early stage breast cancer (n=2967) completed the SF-36 (mental and physical health-related quality of life) and standardized psychosocial questionnaires to assess social support, optimism, hostility, and depression prior to randomization into a dietary trial. Cox regression was performed to assess whether these measures of quality of life and psychosocial functioning predicted time to additional breast cancer events and all-cause mortality; hazard ratios were the measure of association.
There were 492 additional breast cancer events and 301 deaths occurred over a median 7.3 years (range: 0.01–10.8 years) of follow-up. In multivariate models, poorer physical health was associated with both decreased time to additional breast cancer events and all-cause mortality (p trend=0.005 and 0.004, respectively), while greater hostility predicted additional breast cancer events only (p trend=0.03). None of the other psycho-social variables predicted either outcome. The hazard ratios comparing persons with poor (bottom two quintiles) to better (top three quintiles) physical health were 1.42 (95% CI: 1.16, 1.75) for decreased time to additional breast cancer events and 1.37 (95% CI: 1.08, 1.74) for all-cause mortality. Potentially modifiable factors associated with poor physical health included higher BMI, lower physical activity, lower alcohol consumption, and more insomnia (p<0.05 for all).
Interventions to improve physical health should be tested as a means to increase time to additional breast cancer events and mortality among breast cancer survivors.
physical health; breast cancer; oncology; survival
To investigate predictors of exercise adherence to a 12-week exercise intervention for sedentary women and men with elevated blood pressure (BP).
Fifty-one otherwise healthy and unmedicated adults (27 women and 24 men) with elevated BP (≥120/80 mmHg but <179/109 mmHg) participated in a 12-week exercise intervention involving cardiovascular and strength training. Participants kept weekly exercise logs detailing minutes spent exercising each week. The following were assessed before and after the intervention: cardiorespiratory fitness (in mL/kg/min), body mass index (BMI), level of habitual physical activity, physical fatigue, self-efficacy for exercise habits, and social support.
Regression analysis revealed that mean exercise minutes/week were predicted by higher age (p < .05), higher cardiorespiratory fitness (p < .05), and a gender by physical fatigue interaction (p < .01; R2 = 0.34, F < 3.248, p < .01). Women who reported higher physical fatigue prior to the intervention spent more time exercising during the 12-week intervention than those with lower levels of physical fatigue. This relationship persisted after controlling for age, BMI, cardiorespiratory fitness, level of habitual physical activity prior to the intervention, self-efficacy for exercise habits, and social support (p < .01). The gender by physical fatigue interaction explained 13.9% of the variance in mean minutes exercised/week above and beyond the effects of covariates.
Both gender and fatigue should be considered when developing exercise interventions, such that more initial physical fatigue in women is associated with a tendency to devote greater amounts of time to exercising.
exercise; adherence; gender; fatigue
Self-reported diabetes has been associated with poor breast cancer outcomes. Research is needed to investigate the relationship between biologically determined glycemic control and breast cancer prognosis.
Archived baseline blood samples from the Women's Healthy Eating and Living Study were used to measure hemoglobin A1C (HbA1C) among 3,003 survivors of early-stage breast cancer (age of diagnosis, 28 to 70 years) observed for a median of 7.3 years for additional breast cancer events and 10.3 years for all-cause mortality. HbA1C levels provide an accurate, precise measure of chronic glycemic levels. Cox regression analysis was performed to assess whether baseline HbA1C levels predicted disease-free and overall survival.
Only 5.8% of women had chronic hyperglycemia (defined as HbA1C levels ≥ 6.5%). Those with HbA1C ≥ 6.5% were older and more likely to be less educated, have nonwhite ethnicity, be obese, and have more advanced breast cancer at diagnosis. HbA1C was significantly associated with overall survival (Ptrend < .001). After adjusting for confounders, risk of all-cause mortality was twice as high in women with HbA1C ≥ 7.0% compared with women with HbA1C less than 6.5% (hazard ratio [HR], 2.35; 95% CI, 1.56 to 3.54). For disease-free survival, there was a nonsignificant 30% increase in risk for HbA1C levels ≥ 7.0% (HR, 1.26; 95% CI, 0.78 to 2.02). During study follow-up, previously diagnosed rather than undiagnosed diabetes seemed to account for the increased risk.
Chronic hyperglycemia is statistically significantly associated with reduced overall survival in survivors of early-stage breast cancer. Further study of diabetes and its relationship to breast cancer outcomes is warranted.
Dietary intervention trials aim to change dietary patterns of individuals. Participating in such trials could impact dietary self-report in divergent ways: Dietary counseling and training on portion-size estimation could improve self-report accuracy; participant burden could increase systematic error. Such intervention-associated biases could complicate interpretation of trial results. The authors investigated intervention-associated biases in reported total carotenoid intake using data on 3,088 breast cancer survivors recruited between 1995 and 2000 and followed through 2006 in the Women's Healthy Eating and Living Study, a randomized intervention trial. Longitudinal data from 2 self-report methods (24-hour recalls and food frequency questionnaires) and a plasma carotenoid biomarker were collected. A flexible measurement error model was postulated. Parameters were estimated in a Bayesian framework by using Markov chain Monte Carlo methods. Results indicated that the validity (i.e., correlation with “true” intake) of both self-report methods was significantly higher during follow-up for intervention versus nonintervention participants (4-year validity estimates: intervention = 0.57 for food frequency questionnaires and 0.58 for 24-hour recalls; nonintervention = 0.42 for food frequency questionnaires and 0.48 for 24-hour recalls). However, within- and between-instrument error correlations during follow-up were higher among intervention participants, indicating an increase in systematic error. Diet interventions can impact measurement errors of dietary self-report. Appropriate statistical methods should be applied to examine intervention-associated biases when interpreting results of diet trials.
bias (epidemiology); diet; intervention studies; Markov chain Monte Carlo; measurement error; nutrition assessment; reproducibility of results; validity
This analysis was conducted to determine whether comorbid medical conditions predict additional breast cancer events and all-cause mortality in women with a history of early stage breast cancer.
Women (n=2542) participating in a randomized diet trial completed a selfadministered questionnaire regarding whether they were currently being treated for a wide variety of diseases (cardiovascular, diabetes, gallbladder, gastrointestinal, arthritis, and osteoporosis) and conditions (high blood pressure, elevated cholesterol level). Height and weight were measured at baseline. Participants were followed for a median of 7.3 years (range 0.8 to 15.0). Cox regression analysis was performed to assess whether comorbidities predicted disease-free and overall survival; hazard ratio (HR) was the measure of association.
Overall, there were 406 additional breast cancer events and 242 deaths. Participants with diabetes had over 2-fold the risk of additional breast cancer events (HR 2.1, 95% CI: 1.3, 3.4) and mortality (HR 2.5, 95% CI: 1.4, 4.4). The presence of multiple comorbidities did not statistically significantly predict additional breast cancer events. However, compared to no comorbidities, participants with 3 or more comorbidities had a HR of 2.1, 95% CI: 1.3, 3.3 for mortality.
Type 2 diabetes was associated with poor breast cancer prognosis. Given that 85 percent of deaths were caused by breast cancer, these findings suggest that multiple comorbidities may reduce the likelihood of surviving additional breast cancer events.
comorbidities; breast cancer; mortality
Both alcohol consumption and obesity have been linked with breast cancer morbidity and mortality. An inverse association between alcohol intake and obesity suggests possible confounding between these variables (and perhaps other factors) with breast cancer outcomes.
Alcohol intake (beer, wine, spirits, and total) was examined in 3088 women previously diagnosed and treated for breast cancer, within an intervention trial that targeted vegetables, fiber, and fat but not alcohol or weight loss. Factors associated with baseline alcohol intake were included in Cox proportional hazards models for recurrence and mortality.
Alcohol intake was significantly associated with higher education and physical activity levels. Neither light alcohol intake nor obesity was significantly associated with breast cancer recurrence, but moderate alcohol intake > 300 g/month was protective against all-cause mortality (HR = 0.69, CI=0.49-0.97) in a proportional hazards model adjusted for obesity. Obese women were 61% more likely to be nondrinkers than drinkers, and 76% more likely to be light drinkers than moderate/heavy drinkers. In non-obese women, alcohol intake > 10 g/month was associated with lower risk of all-cause mortality (HR = 0.68, 95% CI = 0.51-0.91).
Light alcohol intake, regardless of body weight, did not increase the risk of breast cancer recurrence or all-cause mortality in this cohort of middle-aged women previously diagnosed with breast cancer. Alcohol intake was associated with other favorable prognostic indicators that may explain its apparent protective effect in non-obese women.
alcohol; breast cancer; obesity; mortality; recurrence
Obesity is characterized by chronic mild inflammation and may influence the risk and progression of cancer.
The current study is an exploratory analysis of the effect of a weight loss intervention that emphasized increased physical activity on inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) at the end of the 16-week intervention period in overweight breast cancer survivors.
Study participants averaged 56 years of age (N = 68). Intervention participants (n = 44 vs. 24 controls) participated in a cognitive behavioral therapy-based weight management program as part of an exploratory randomized trial. The intervention incorporated strategies to promote increased physical activity and diet modification. Baseline and 16-week data included height, weight, body composition, physical activity level, and biomarkers IL-6, IL-8, TNF-α, and VEGF.
Weight loss was significantly greater in the intervention group than controls (−5.7 [3.5] vs. 0.2 [4.1] kg, P < 0.001). Paired t tests noted favorable changes in physical activity level (P < 0.001 intervention, P = 0.70 control), marginally lower IL-6 levels (P = 0.06 intervention, P = 0.25 control) at 16 weeks for participants in the intervention group, and lower TNF-α levels for participants in the intervention (P < 0.05) and control groups (P < 0.001). Increased physical activity was associated with favorable changes in IL-6 for participants in the intervention group (R2 = 0.18; P < 0.03).
Favorable changes in cytokine levels were observed in association with weight loss in this exploratory study with overweight breast cancer survivors.
Weight loss; Physical activity; Exercise; Inflammatory factors; Obesity; Breast cancer survivors
The validity of self-reported dietary intake is critical to the design and interpretation of diet-disease investigations. For many nutrients, there are no ideal methods to establish validity, given correlated error between reference and assessment tools, and constraints on time and resources available to perform such studies. Therefore, we quantified associations between macronutrient intakes and plasma HDL-cholesterol and TAG, relying on known associations between these factors to test the criterion validity of the FFQ used in the Multi-Ethnic Study of Atherosclerosis (MESA). Baseline dietary macronutrient intakes (derived from 120-item FFQ), and fasting plasma HDL and TAG were measured in 4510 MESA participants, aged 45–84 years. After adjusting for non-dietary factors known to affect plasma lipid concentrations, greater carbohydrate intake was associated with lower HDL and higher TAG (β per 5-unit change in percentage energy intake from carbohydrate = −5 (se 1) mg/l (P<0·001) for HDL and 15 (se 6) mg/l (P=0·008) for TAG), whereas higher energy intake from fat was associated with higher HDL and lower TAG (β per 5-unit change in percentage energy from fat = 3·7 (se 2) mg/l (P=0·01) for HDL and β = 19 (se 7) mg/l (P=0·004) for TAG). Associations of dietary carbohydrate and fat intakes with HDL and TAG concentrations were consistent with previous studies, demonstrating criterion validity of these dietary measures in the MESA.
FFQ; Criterion validity; Plasma lipids; Macronutrients
Research suggests that physical activity is associated with improved breast cancer survival, yet no studies have examined the association between post-diagnosis changes in physical activity and breast cancer outcomes. The aim of this study was to determine whether baseline activity and 1-year change in activity are associated with breast cancer events or mortality.
A total of 2,361 post-treatment breast cancer survivors (Stage I–III) enrolled in a randomized controlled trial of dietary change completed physical activity measures at baseline and one year. Physical activity variables (total, moderate–vigorous, and adherence to guidelines) were calculated for each time point. Median follow-up was 7.1 years. Outcomes were invasive breast cancer events and all-cause mortality.
Those who were most active at baseline had a 53% lower mortality risk compared to the least active women (HR = 0.47; 95% CI: 0.26, 0.84; p = .01). Adherence to activity guidelines was associated with a 35% lower mortality risk (HR = 0.65, 95% CI: 0.47, 0.91; p < .01). Neither baseline nor 1-year change in activity was associated with additional breast cancer events.
Higher baseline (post-treatment) physical activity was associated with improved survival. However, change in activity over the following year was not associated with outcomes. These data suggest that long-term physical activity levels are important for breast cancer prognosis.
Exercise; Recurrence; Survival; Behavior; Lifestyle
Reducing the concentration of polyamines (spermine, spermidine, and putrescine) in the body pool may slow the cancer process. Because dietary spermine, spermidine, and putrescine contribute to the body pool of polyamines, quantifying them in the diet is important. Limited information about polyamine content of food is available, especially for diets in the United States. This brief report describes the development of a polyamine database linked to the Fred Hutchinson Cancer Center food frequency questionnaire (FFQ). Values for spermine, spermidine, and putrescine were calculated and reported per serving size (nmol/serving). Of the foods from the database that were evaluated, fresh and frozen corn contain the highest levels of putrescine (560,000 nmol/serving and 902,880 nmol/serving) and spermidine (137,682 nmol/serving and 221,111 nmol/serving), and green pea soup contains the highest concentration of spermine (36,988 nmol/serving). The polyamine database and FFQ were tested with a convenience sample (n=165). Average daily polyamine intakes from the sample were: 159,133 nmol/day putrescine, 54,697 nmol/day spermidine, and 35,698 nmol/day spermine. Orange and grapefruit juices contributed the greatest amount of putrescine (44,441 nmol/day) to the diet. Green peas contributed the greatest amount of spermidine (3,283 nmol/day) and ground meat contributed the greatest amount of spermine (2,186 nmol/day). Development of this database linked to an FFQ provides a means of estimating polyamine intake and contributes to investigations relating polyamines to cancer.
Breast cancer survivors not only experience distressing physical symptoms associated with treatments, but also are faced with psychosocial challenges. Despite growing scientific evidence that physical activity (PA) may mitigate psychosocial distress experienced by women treated for breast cancer, the literature is equivocal.
This study investigated the relationships between cardiorespiratory fitness (CRF), PA, and psychosocial factors in breast cancer survivors.
Data involving overweight or obese breast cancer survivors (N = 260) were examined. CRF was determined by a submaximal graded exercise test. PA, depressive symptoms, total fatigue, and global self-esteem were assessed with self-report measures. Pearson's correlations were conducted to determine associations among CRF, PA, depressive symptoms, total fatigue, and global self-esteem. Multiple regression models, with age and body mass index as covariates, were performed using continuous levels for CRF and PA.
Bivariate correlations suggested that CRF and PA were unrelated to the psychosocial variables. One of the regression models identified a marginally significant (P = 0.06) inverse association between depressive symptoms and PA.
CRF and PA were not associated with psychosocial factors in this sample of breast cancer survivors. However, minimal PA was reported by the majority of participants, so low PA variability likely influenced these findings.
Breast cancer survivors; Physical activity; Cardiorespiratory fitness; Psychosocial health
In some cohort studies, a high-vegetable diet has been associated with greater likelihood of recurrence-free survival in women diagnosed with breast cancer. Carotenoids are obtained primarily from vegetables and fruit, and they exhibit biological activities that may specifically reduce the progression of mammary carcinogenesis. The present analysis examines the relationship between plasma carotenoids at enrollment and 1, 2 or 3, 4 and 6 years and breast cancer-free survival in the Women’s Healthy Eating and Living (WHEL) Study participants (n = 3043), who had been diagnosed with early stage breast cancer. The primary endpoint was time to a second breast cancer event (a recurrence or new primary breast cancer). An average carotenoid concentration over time was estimated for each participant as the average area under the plasma carotenoid curve (AUC) formed by the plasma carotenoid concentrations at scheduled clinic visits. Multiple regression Cox proportional hazards analysis with adjustment for prognostic and other factors was used to examine the association between carotenoids and breast cancer-free survival. A total of 508 (16.7%) breast cancer events occurred over a median 7.12 years follow-up. Compared to the lowest tertile, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval 0.54–0.83) after adjustment. The interaction between study group and tertile of average carotenoid concentration over time was not significant (P = 0.23). Higher biological exposure to carotenoids, when assessed over the time frame of the study, was associated with greater likelihood of breast cancer-free survival regardless of study group assignment.
Carotenoids; Diet; Breast Cancer; Survival; Cohort
To determine whether a low-fat diet high in vegetables, fruit, and fiber differentially affects prognosis in breast cancer survivors with hot flashes (HF) or without HF after treatment.
Patients and Methods
A secondary analysis was conducted on 2,967 breast cancer survivors, age 18 to 70 years, who were randomly assigned between 1995 and 2000 in a multicenter, controlled trial of a dietary intervention to prevent additional breast cancer events and observed through June 1, 2006. We compared the dietary intervention group with a group who received five-a-day dietary guidelines.
Independent of HF status, a substantial between-group difference among those who did and did not receive dietary guidelines was achieved and maintained at 4 years in intake of vegetable/fruit servings per day (54% higher; 10 v 6.5 servings/d, respectively), fiber (31% higher; 25.5 v 19.4 g/d, respectively), and percent energy from fat (14% lower; 26.9% v 31.3%, respectively). Adjusting for tumor characteristics and antiestrogen treatment, HF-negative women assigned to the intervention had 31% fewer events than HF-negative women assigned to the comparison group (hazard ratio [HR] = 0.69; 95% CI, 0.51 to 0.93; P = .02). The intervention did not affect prognosis in the women with baseline HFs. Furthermore, compared with HF-negative women assigned to the comparison group, HF-positive women had significantly fewer events in both the intervention (HR = 0.77; 95% CI, 0.59 to 1.00; P = .05) and comparison groups (HR = 0.65; 95% CI, 0.49 to 0.85; P = .002).
A diet with higher vegetable, fruit, and fiber and lower fat intakes than the five-a-day diet may reduce risk of additional events in HF-negative breast cancer survivors. This suggestive finding needs confirmation in a trial in which it is the primary hypothesis.
Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01−1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03−1.53), and free estradiol (HR, 1.31; 95% CI, 1.03−1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer.
The reliability of biomarkers profoundly impacts validity of their use in epidemiology and can have serious implications for study power and the ability to find true associations. We assessed reliability of plasma carotenoid levels over time and how it could influence study power through sample size and effect-size.
Plasma carotenoid levels were measured in a cohort study of 1323 women participating in the control arm of the Women's Healthy Eating and Living Study. We compared mean plasma levels at baseline, year 1, and year 4 of the study for alpha-carotene, beta-carotene, lycopene, lutein, and beta-cryptoxanthin. Reliability of these levels over time was assessed by Spearman correlations and intraclass correlation.
We found limited variation in mean levels between any 2 time points. Variation did not exceed 8% for lycopene, lutein, and beta-cryptoxanthin, 15% for alpha-carotene, and 18% for beta-carotene. Spearman correlations for individual carotenoids over time varied between 0.50 and 0.80, with lycopene having the lowest correlation. Intraclass correlations ranged from 0.47 to 0.66 for carotenoids.
Intraclass correlations for plasma carotenoids over a period of several years are acceptable for epidemiologic studies. However, such variation is enough to decrease statistical power and increase the sample size needed to detect a given effect.
We examined the effect of dietary energy density change on body weight in participants of a randomized trial. Intervention participants markedly increased fruit and vegetable intake while reducing energy intake from fat. Participants were 2,718 breast cancer survivors, aged 26−74 yr, with baseline mean body mass index of 27.3 kg/m2 (SD = 6.3). We assessed dietary intake by sets of four 24-h dietary recalls and validated with plasma carotenoid concentrations. Weight and height were measured at baseline, 1 yr, and 4 yr. Dietary energy density was calculated using food but excluding beverages. Intervention participants significantly reduced dietary energy density compared to controls and maintained it over 4 yr—both in cross-sectional (P < 0.0001) and longitudinal (Group × Time interaction, P < 0.0001) analyses. Total energy intake or physical activity did not vary between groups. The intervention group had a small but significant weight loss at 1 yr (Group × Time interaction, P < 0.0001), but no between-group weight difference was observed at 4 yr. Our study showed that reducing dietary energy density did not result in a reduction in total energy intake and suggests that this strategy alone is not sufficient to promote long-term weight loss in a free-living population.
Many individual risk factors for insomnia have been identified for women with a history of breast cancer. We assessed the relative importance of a wide range of risk factors for insomnia in this population.
Two thousand six hundred and forty-five women ≤4 years post-treatment for Stage I (≥1 cm)–IIIA breast cancer provided data on cancer-related variables, personal characteristics, health behaviors, physical health/symptoms, psychosocial variables, and the Women's Health Initiative-Insomnia Rating Scale (WHI-IRS; scores ≥9 indicate clinically significant insomnia).
Thirty-nine per cent had elevated WHI-IRS scores. In binary logistic regression, the variance in high/low insomnia group status accounted for by each risk factor category was: cancer-specific variables, 0.4% (n.s.); personal characteristics, 0.9% (n.s.); health behaviors, 0.6% (n.s.); physical health/symptoms, 13.4% (p < 0.001); and, psychosocial factors, 11.4% (p < 0.001). Insomnia was associated with worse depressive (OR = 1.32) and vasomotor symptoms (particularly night sweats) (OR = 1.57).
Various cancer-specific, demographic, health behavior, physical health, and psychosocial factors have been previously reported as risk factors for insomnia in breast cancer. In our study (which was powered for simultaneous examination of a variety of variables), cancer-specific, health behavior, and other patient variables were not significant risk factors when in the presence of physical health and psychosocial variables. Only worse depressive and vasomotor symptoms were meaningful predictors.
breast cancer; insomnia; depression; mood; vasomotor symptoms; night sweats; hot flashes; quality of life