Educating the Next Generation of Undergraduate URM Cancer Scientists: Results and Lessons Learned from a Cancer Research Partnership Scholar Program.

To improve cancer disparities among under-represented minority (URM) populations, better representation of URM individuals in cancer research is needed. The San Diego State University and University of California San Diego Moores Cancer Center Partnership is addressing cancer disparities through an educational program targeting undergraduate URM students. The Partnership provides a paid intensive summer research internship enriched with year-round activities that include educational sessions, a journal club, mentorship, social activities, and poster sessions and presentations. Program evaluation through follow-up surveys, focus groups, and other formal and informal feedback, including advisory and program steering committees, are used to improve the program. Long-term follow-up among scholars (minimum of 10 years) provides data to evaluate the program's long-term impact on scholars' education and career path. Since 2016, 63 URM undergraduate students participated in the scholar program. At the year-2 follow-up (2016 cohort; n = 12), 50% had completed their Graduate Record Examination (GRE) and/or applied to graduate or medical school. Lessons learned during the course of the program led to implementation of changes to provide a better learning experience and increase overall program satisfaction. Updates were made to recruitment timeline, improvements of the recruitment processes, refinement of the program contracts and onboarding meetings, identification of essential program coordinator skills and responsibilities, adjustments to program components, and establishment of a well-mapped and scheduled evaluation plan. The Partnership identified best practices and lessons learned for implementing lab-based internship scholar programs in biomedical and public health fields that could be considered in other programs.

Effects of Pistachio Consumption in a Behavioral Weight Loss Intervention on Weight Change, Cardiometabolic Factors, and Dietary Intake.

Epidemiological studies have linked regular nut consumption with lower body mass index and reduced likelihood of weight gain in adulthood. Nuts can displace other foods in the diet, and thus, promote a healthier dietary pattern. The purpose of this study was to examine the effect of pistachio nut consumption in overweight/obese adults. This randomized controlled study enrolled non-diabetic overweight/obese adults (n = 100) assigned to a 4-month behavioral weight loss intervention only group (controls) or also prescribed 1.5 oz/day (42 g/day) of pistachios (pistachio group). Outcomes were change in body weight, cardiometabolic factors, and dietary intake. Percent weight change was similar in the two groups (-5.1 [0.5] (mean [SE])% in the control group and -4.9 [0.6]% in the pistachio group, and body mass index (BMI) and waist circumference were reduced in both groups (time effect p ≤ 0.05). The pistachio group (but not the control group) exhibited a significant reduction in both systolic and diastolic blood pressure (time effect p = 0.01). Plasma alpha-carotene, beta-carotene, and lutein concentrations increased significantly in the pistachio group (time effect p < 0.05). Pistachio consumption was associated with increased dietary fiber intake and decreased consumption of sweets. Regular consumption of pistachios was associated with a comparable degree of weight loss, and similar reductions in BMI and waist circumference, in overweight/obese men and women compared to controls, and favorable changes in the diet, in the context of a behavioral weight loss intervention.

Walnut consumption in a weight reduction intervention: effects on body weight, biological measures, blood pressure and satiety.

BACKGROUND: Dietary strategies that help patients adhere to a weight reduction diet may increase the likelihood of weight loss maintenance and improved long-term health outcomes. Regular nut consumption has been associated with better weight management and less adiposity. The objective of this study was to compare the effects of a walnut-enriched reduced-energy diet to a standard reduced-energy-density diet on weight, cardiovascular disease risk factors, and satiety. METHODS: Overweight and obese men and women (n = 100) were randomly assigned to a standard reduced-energy-density diet or a walnut-enriched (15% of energy) reduced-energy diet in the context of a behavioral weight loss intervention. Measurements were obtained at baseline and 3- and 6-month clinic visits. Participants rated hunger, fullness and anticipated prospective consumption at 3 time points during the intervention. Body measurements, blood pressure, physical activity, lipids, tocopherols and fatty acids were analyzed using repeated measures mixed models. RESULTS: Both study groups reduced body weight, body mass index and waist circumference (time effect p < 0.001 for each). Change in weight was -9.4 (0.9)% vs. -8.9 (0.7)% (mean [SE]), for the standard vs. walnut-enriched diet groups, respectively. Systolic blood pressure decreased in both groups at 3 months, but only the walnut-enriched diet group maintained a lower systolic blood pressure at 6 months. The walnut-enriched diet group, but not the standard reduced-energy-density diet group, reduced total cholesterol and low-density lipoprotein cholesterol (LDL-C) at 6 months, from 203 to 194 mg/dL and 121 to 112 mg/dL, respectively (p < 0.05). Self-reported satiety was similar in the groups. CONCLUSIONS: These findings provide further evidence that a walnut-enriched reduced-energy diet can promote weight loss that is comparable to a standard reduced-energy-density diet in the context of a behavioral weight loss intervention. Although weight loss in response to both dietary strategies was associated with improvements in cardiovascular disease risk factors, the walnut-enriched diet promoted more favorable effects on LDL-C and systolic blood pressure. TRIAL REGISTRATION: The trial is registered at ( NCT02501889 ).

A walnut-containing meal had similar effects on early satiety, CCK, and PYY, but attenuated the postprandial GLP-1 and insulin response compared to a nut-free control meal.

Regular nut consumption is associated with lower adiposity and reduced weight gain in adulthood. Walnut feeding studies have observed minimal effect on body weight despite potential additional energy intake. Several mechanisms may explain why consuming nuts promotes weight control, including increased early phase satiety, possibly reflected in postprandial response of gastrointestinal and pancreatic peptides hypothesized to affect appetite. The purpose of this study was to compare postprandial insulin, glucagon and gastrointestinal peptide response and satiety following a meal with ∼54% of energy from walnuts or cream cheese, using a within-subject crossover study design in overweight/obese adults (N = 28). Sixty minutes after the walnut-containing meal, glucagon-like peptide-1 was lower than after the reference meal (p=0.0433), and peptide YY, cholecystokinin and ghrelin did not differ after the two meals. Sixty and 120 min after the walnut-containing meal, pancreatic polypeptide (p = 0.0014 and p = 0.0002) and glucose-dependent insulinotropic peptide (p < 0.0001 and p = 0.0079) were lower than after the reference meal, and 120 min after the walnut-containing meal, glucagon was higher (p=0.0069). Insulin and C-peptide increased at 60 min in response to both meals but were lower at 120 min after the walnut-containing meal (p=0.0349 and 0.0237, respectively). Satiety measures were similar after both meals. These findings fail to support the hypothesis that acute postprandial gastrointestinal peptide response to a walnut-containing meal contributes to increased satiety. However, inclusion of walnuts attenuated the postprandial insulin response, which may contribute to the more favorable lipid profile observed in association with regular walnut consumption.

The IL-6 Gene Promoter SNP and Plasma IL-6 in Response to Diet Intervention.

We recently reported that interleukin-6 (IL-6), an inflammatory marker associated with breast pathology and the development of breast cancer, decreases with diet intervention and weight loss in both insulin-sensitive and insulin-resistant obese women. Here, we tested whether an individual's genotype at an IL6 SNP, rs1800795, which has previously been associated with circulating IL-6 levels, contributes to changes in IL-6 levels or modifies the effect of diet composition on IL-6 in these women. We genotyped rs1800795 in overweight/obese women (N = 242) who were randomly assigned to a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich (18% energy), higher fat (35% energy), lower carbohydrate (45% energy) diet in a 1-year weight loss intervention study of obesity-related biomarkers for breast cancer incidence and mortality. Plasma IL-6 levels were measured at baseline, 6 and 12 months. At baseline, individuals with a CC genotype had significantly lower IL-6 levels than individuals with either a GC or GG genotype (p < 0.03; 2.72 pg/mL vs. 2.04 pg/mL), but this result was not significant when body mass index (BMI) was accounted for; the CC genotype group had lower BMI (p = 0.03; 32.5 kg/m² vs. 33.6 kg/m²). We did not observe a 2-way interaction of time*rs1800795 genotype or diet*rs1800795 genotype. Our findings provide evidence that rs1800795 is associated with IL-6 levels, but do not support a differential interaction effect of rs1800795 and diet composition or time on changes in circulating IL-6 levels. Diet intervention and weight loss are an important strategy for reducing plasma IL-6, a risk factor of breast cancer in women, regardless of their rs1800795 genotype.

Effects of diet composition on weight loss, metabolic factors and biomarkers in a 1-year weight loss intervention in obese women examined by baseline insulin resistance status.

BACKGROUND: Obesity is a risk factor for postmenopausal breast cancer incidence and premenopausal and postmenopausal breast cancer mortality, which may be explained by several metabolic and hormonal factors (sex hormones, insulin resistance, and inflammation) that are biologically related. Differential effects of dietary composition on weight loss and these metabolic factors may occur in insulin-sensitive vs. insulin-resistant obese women. OBJECTIVE: To examine the effect of diet composition on weight loss and metabolic, hormonal and inflammatory factors in overweight/obese women stratified by insulin resistance status in a 1-year weight loss intervention. METHODS AND RESULTS: Nondiabetic women who were overweight/obese (n=245) were randomly assigned to a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich (18% energy), higher fat (35% energy), lower carbohydrate (45% energy) diet. All groups lost weight at follow-up (P<0.0001), with mean (SEM) percent loss of 9.2(1.1)% in lower fat, 6.5(0.9)% in lower carbohydrate, and 8.2(1.0)% in walnut-rich groups at 12months. The diet×time×insulin resistance status interaction was not statistically significant in the model for overall weight loss, although insulin sensitive women at 12months lost more weight in the lower fat vs. lower carbohydrate group (7.5kg vs. 4.3kg, P=0.06), and in the walnut-rich vs. lower carbohydrate group (8.1kg vs. 4.3kg, P=0.04). Sex hormone binding globulin increased within each group except in the lower carbohydrate group at 12months (P<0.01). C-reactive protein and interleukin-6 decreased at follow-up in all groups (P<0.01). CONCLUSIONS: Findings provide some support for differential effects of diet composition on weight loss depending on insulin resistance status. Prescribing walnuts is associated with weight loss comparable to a standard lower fat diet in a behavioral weight loss intervention. Weight loss itself may be the most critical factor for reducing the chronic inflammation associated with increased breast cancer risk and progression.

Randomized clinical trial of portion-controlled prepackaged foods to promote weight loss.

OBJECTIVE: Providing portion-controlled prepackaged foods in a behavioral counseling intervention may promote more weight and fat loss than a standard self-selected diet. METHODS: The primary aim was to test whether providing portion-controlled prepackaged lunch and dinner entrées within a behavioral weight loss intervention promotes greater weight loss at 12 weeks compared to self-selected foods in adults with overweight/obesity. Other aims were to examine effects on biological factors, fitness, and meal satisfaction. One-half of those assigned to prepackaged entrées were provided items with a higher protein level (>25% energy) as an exploratory aim. RESULTS: Participants (N = 183) had a baseline weight of 95.9 (15.6) kg (mean [SD]) and BMI of 33.2 (3.5) kg/m(2) . Weight data at 12 weeks were available for 180 subjects. Weight loss for regular entrée, higher protein entrée, and control groups was 8.6 (3.9)%, 7.8 (5.1)%, and 6.0 (4.4)%, respectively (P < 0.05, intervention vs. control). Intervention participants lost more body fat than controls (5.7 [3.4] vs. 4.4 [3.3] kg, P < 0.05). CONCLUSIONS: A meal plan incorporating portion-controlled prepackaged entrées promotes greater weight and fat loss than a standard self-selected diet, with comparable meal satisfaction. Initial weight loss predicts long-term weight loss so these results are relevant to likelihood of longer term success.

Impact of a behavioral weight loss intervention on comorbidities in overweight and obese breast cancer survivors.

PURPOSE: Comorbid medical conditions are common among breast cancer survivors, contribute to poorer long-term survival and increased overall mortality, and may be ameliorated by weight loss. This secondary analysis evaluated the impact of a weight loss intervention on comorbid medical conditions immediately following an intervention (12 months) and 1-year postintervention (24 months) using data from the Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial-a phase III trial which was aimed at and successfully promoted weight loss. METHODS: ENERGY randomized 692 overweight/obese women who had completed treatment for early stage breast cancer to either a 1-year group-based behavioral intervention designed to achieve and maintain weight loss or to a less intensive control intervention. Minimal support was provided postintervention. New medical conditions, medical conditions in which non-cancer medications were prescribed, hospitalizations, and emergency room visits, were compared at baseline, year 1, and year 2. Changes over time were analyzed using chi-squared tests, Kaplan-Meier, and logistic regression analyses. RESULTS: At 12 months, women randomized to the intervention had fewer new medical conditions compared to the control group (19.6 vs. 32.2 %, p < 0.001); however, by 24 months, there was no longer a significant difference. No difference was observed in each of the four conditions for which non-cancer medications were prescribed, hospital visits, or emergency visits at either 12 or 24 months. CONCLUSIONS: These results support a short-term benefit of modest weight loss on the likelihood of comorbid conditions; however, recidivism and weight regain likely explain no benefit at 1-year postintervention follow-up.

Effects of Diet Composition and Insulin Resistance Status on Plasma Lipid Levels in a Weight Loss Intervention in Women.

BACKGROUND: Optimal macronutrient distribution of weight loss diets has not been established. The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies, and insulin resistance status may interact with diet composition and affect weight loss and lipid responses. METHODS AND RESULTS: Overweight and obese women (n=245) were enrolled in a 1-year behavioral weight loss intervention and randomly assigned to 1 of 3 study groups: a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich, higher fat (35% energy), lower carbohydrate (45% energy) diet. Blood samples and data available from 213 women at baseline and at 6 months were the focus of this analysis. Triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterol were quantified and compared between and within groups. Triglycerides decreased in all study arms at 6 months (P<0.05). The walnut-rich diet increased high-density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet (P<0.05). The walnut-rich diet also reduced low-density lipoprotein cholesterol in insulin-sensitive women, whereas the lower fat diet reduced both total cholesterol and high-density lipoprotein cholesterol in insulin-sensitive women (P<0.05). Insulin sensitivity and C-reactive protein levels also improved. CONCLUSIONS: Weight loss was similar across the diet groups, although insulin-sensitive women lost more weight with a lower fat, higher carbohydrate diet versus a higher fat, lower carbohydrate diet. The walnut-rich, higher fat diet resulted in the most favorable changes in lipid levels. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01424007.

Correlates of quality of life in overweight or obese breast cancer survivors at enrollment into a weight loss trial.

OBJECTIVE: The purpose of this analysis was to examine the correlates of the physical and psychosocial domains of quality of life (QOL) in a cohort of breast cancer survivors participating in a weight loss intervention trial. METHODS: Correlates of QOL and psychosocial functioning were examined in 692 overweight or obese breast cancer survivors at entry into a weight loss trial. QOL was explored with three measures: Short-form 36 (SF-36), Impact of Cancer scale (IOC), and the Breast Cancer Prevention Trial (BCPT) symptom scales. Available data included information on weight and physical activity, as well as demographic and medical characteristics. Multivariate analyses were used to identify associations adjusted for other characteristics. RESULTS: In multivariate analysis, younger age was associated with higher negative impact scores (p < 0.0001). Hispanic, African-American, and Asian women had higher positive IOC impact scores compared with White non-Hispanic women (p < 0.01). Increased number of comorbidities was associated with lower physical and mental QOL scores (p < 0.01). Body mass index was not independently associated with QOL measures. Physical activity was directly associated with physical and mental QOL and IOC positive impact, and inversely related to IOC negative impact and Breast Cancer Prevention Trial symptom scales. CONCLUSIONS: Quality-of-life measures in breast cancer survivors are differentially associated with demographic and other characteristics. When adjusted for these characteristics, degree of adiposity among overweight or obese women does not appear to be independently associated with QOL. Among overweight or obese breast cancer survivors, higher level of physical activity is associated with higher QOL across various scales and dimensions.

Physical activity levels of overweight or obese breast cancer survivors: correlates at entry into a weight loss intervention study.

PURPOSE: Physical activity is associated with reduced risk and progression of breast cancer, and exercise can improve physical function, quality of life, and fatigue in cancer survivors. Evidence on factors associated with cancer survivors' adherence to physical activity guidelines from the American Cancer Society and the U.S. Department of Health and Human Services is mixed. This study seeks to help fill this gap in knowledge by examining correlates with physical activity among breast cancer survivors. METHODS: Overweight or obese breast cancer survivors (N = 692) were examined at enrollment into a weight loss intervention study. Questionnaires and medical record review ascertained data on education, race, ethnicity, menopausal status, physical activity, and medical history. Measures of anthropometrics and fitness level were conducted. Regression analysis examined associations between physical activity and demographic, clinical, and lifestyle factors. RESULTS: Overall, 23% of women met current guidelines. Multivariate analysis revealed that body mass index (p = 0.03), emergency room visits in the past year (p = 0.04), and number of comorbidities (p = 0.02) were associated with less physical activity. Geographic region also was associated with level of physical activity (p = 0.02), with women in Alabama reporting significantly less activity than those in other participating regions. CONCLUSIONS: The majority of overweight/obese breast cancer survivors did not meet physical activity recommendations. Physical activity levels were associated with degree of adiposity, geographic location, and number of comorbidities. The majority of overweight breast cancer survivors should be encouraged to increase their level of physical activity. Individualizing exercise prescriptions according to medical comorbidities may improve adherence.

Quality of life outcomes from the Exercise and Nutrition Enhance Recovery and Good Health for You (ENERGY)-randomized weight loss trial among breast cancer survivors.

Obesity is a poor prognostic factor and is negatively related to quality of life (QOL) in breast cancer survivors. Exercise and Nutrition to Enhance Recovery and Good Health for You is the largest weight loss trial completed among cancer survivors. Percent losses in body weight with an intensive group-based intervention versus an attention control were 6.0 versus 1.5 % (p < 0.0001) and 3.7 versus 1.3 % (p < 0.0001) at 12 and 24 months, respectively. ENERGY also was designed to answer the research question: Does weight loss significantly improve vitality and physical function (key components of QOL)? 692 breast cancer survivors (BMI: 25-45 kg/m(2)) at 4 US sites were randomized to a year-long intensive intervention of 52 group sessions and telephone counseling contacts versus a non-intensive (control) of two in-person counseling sessions. Weight, self-reported QOL, and symptoms were measured semi-annually for two years. Significant decreases in physical function and increases in symptoms were observed among controls from baseline to 6 months, but not in the intervention arm, -3.45 (95 % Confidence Interval [CI] -6.10, -0.79, p = 0.0109) and 0.10 (95 %CI 0.04, 0.16, p = 0.0021), respectively. Improvements in vitality were seen in both arms but trended toward greater improvement in the intervention arm -2.72 (95 % CI -5.45, 0.01, p = 0.0508). These differences diminished over time; however, depressive symptoms increased in the intervention versus control arms and became significant at 24 months, -1.64 (95 % CI -3.13, -0.15, p = 0.0308). Increased QOL has been reported in shorter term diet and exercise trials among cancer survivors. These longer term data suggest that diet and exercise interventions improve some aspects of QOL, but these benefits may diminish over time.

Results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial: A Behavioral Weight Loss Intervention in Overweight or Obese Breast Cancer Survivors.

PURPOSE: Obesity increases risk for all-cause and breast cancer mortality and comorbidities in women who have been diagnosed and treated for breast cancer. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is the largest weight loss intervention trial among survivors of breast cancer to date. METHODS: In this multicenter trial, 692 overweight/obese women who were, on average, 2 years since primary treatment for early-stage breast cancer were randomly assigned to either a group-based behavioral intervention, supplemented with telephone counseling and tailored newsletters, to support weight loss or a less intensive control intervention and observed for 2 years. Weight and blood pressure were measured at 6, 12, 18, and 24 months. Longitudinal mixed models were used to analyze change over time. RESULTS: At 12 months, mean weight loss was 6.0% of initial weight in the intervention group and 1.5% in the control group (P<.001). At 24 months, mean weight loss in the intervention and control groups was 3.7% and 1.3%, respectively (P<.001). Favorable effects of the intervention on physical activity and blood pressure were observed. The weight loss intervention was more effective among women older than 55 years than among younger women. CONCLUSION: A behavioral weight loss intervention can lead to clinically meaningful weight loss in overweight/obese survivors of breast cancer. These findings support the need to conduct additional studies to test methods that support sustained weight loss and to examine the potential benefit of intentional weight loss on breast cancer recurrence and survival.

Mediation of Weight Loss and Weight Loss Maintenance through Dietary Disinhibition and Restraint.

Understanding the degree to which eating behaviors, such as disinhibition and restraint, are associated with weight loss and weight loss maintenance could contribute to further refinement of effective weight management intervention strategies. The purpose of this analysis was to examine if these factors mediate weight loss or weight loss maintenance using data from a randomized controlled trial testing a commercial weight loss program that delivered behavioral counseling and structured meal plans including prepackaged foods. Mediation analyses were used to examine whether changes in disinhibition and restraint mediated the relationship between intervention and weight change during initial weight loss (0-6 months), continued weight loss (6-12 months), or weight loss maintenance (12-24 months) phases. Only decreases in disinhibition between baseline and 6 months mediated the intervention effect on initial weight loss. Our results suggest the mediation effects of these eating behaviors are modest and other factors contribute to a larger, more complex long-term weight loss prognosis.

Weight loss, glycemic control, and cardiovascular disease risk factors in response to differential diet composition in a weight loss program in type 2 diabetes: a randomized controlled trial.

OBJECTIVE: To test whether a weight loss program promotes greater weight loss, glycemic control, and improved cardiovascular disease risk factors compared with control conditions and whether there is a differential response to higher versus lower carbohydrate intake. RESEARCH DESIGN AND METHODS: This randomized controlled trial at two university medical centers enrolled 227 overweight or obese adults with type 2 diabetes and assigned them to parallel in-person diet and exercise counseling, with prepackaged foods in a planned menu during the initial phase, or to usual care (UC; two weight loss counseling sessions and monthly contacts). RESULTS: Relative weight loss was 7.4% (95% CI 5.7-9.2%), 9.0% (7.1-10.9%), and 2.5% (1.3-3.8%) for the lower fat, lower carbohydrate, and UC groups (P < 0.001 intervention effect). Glycemic control markers and triglyceride levels were lower in the intervention groups compared with UC group at 1 year (fasting glucose 141 [95% CI 133-149] vs. 159 [144-174] mg/dL, P = 0.023; hemoglobin A1c 6.9% [6.6-7.1%] vs. 7.5% [7.1-7.9%] or 52 [49-54] vs. 58 [54-63] mmol/mol, P = 0.001; triglycerides 148 [134-163] vs. 204 [173-234] mg/dL, P < 0.001). The lower versus higher carbohydrate groups maintained lower hemoglobin A1c (6.6% [95% CI 6.3-6.8%] vs. 7.2% [6.8-7.5%] or 49 [45-51] vs. 55 [51-58] mmol/mol) at 1 year (P = 0.008). CONCLUSIONS: The weight loss program resulted in greater weight loss and improved glycemic control in type 2 diabetes.

Predictors of improvement in cardiometabolic risk factors with weight loss in women.

BACKGROUND: Weight loss is associated with improvements in cardiometabolic risk factors, including serum glucose, insulin, C-reactive protein, and blood lipids. Few studies have evaluated the long-term (>18 months) effect of weight loss on these risk factors or sought to identify factors associated with sustained improvements in these measures. METHODS AND RESULTS: In 417 overweight/obese women (mean [SD] age, 44 [10] years) participating in a weight loss trial, we sought to identify predictors of weight loss-associated cardiometabolic risk factors after 12 and 24 months of intervention. Total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol (LDL-C), high-density lipoprotein (HDL)-cholesterol, non-HDL-cholesterol, triglycerides (TG), insulin, glucose, C-reactive protein (CRP), and cardiopulmonary fitness were measured at baseline and at 12 and 24 months. After 24 months, significant reductions in body weight, waist circumference, CRP, TC, HDL-cholesterol, and non-HDL-cholesterol were observed (P<0.01). After 24 months, mean TC and non-HDL-cholesterol were reduced regardless of the amount of weight lost, whereas reductions in LDL-cholesterol, CRP, insulin, and TG were observed only in those who lost ≥10% body weight. Step-test performance improved only in those who lost ≥10% body weight after 24 months. Change in weight demonstrated a positive predictive value for change in cholesterol, insulin, glucose, and triglycerides. Baseline level of the biomarker showed the greatest predictive value for follow-up measures for insulin, cholesterol, glucose, and triglycerides. CONCLUSIONS: Our data extend the results from short-term weight loss trials and suggest that the magnitude of weight loss and baseline values for risk factors are associated with improvements in cardiometabolic risk factors even after 24 months. CLINICAL TRIALS REGISTRATION INFORMATION URL: http://www.clinicaltrials.gov/. Unique identifier: NCT00640900.

Favorable changes in serum estrogens and other biologic factors after weight loss in breast cancer survivors who are overweight or obese.

BACKGROUND: Obesity is associated with an increased risk for recurrence and all-cause mortality in breast cancer survivors. Excess adiposity is associated with increased estrogen, insulin, and leptin, and with decreased sex hormone binding globulin (SHBG) concentrations, which may promote breast cancer progression and recurrence. This study aimed to assess the effects of weight loss on these factors. PATIENTS AND METHODS: Breast cancer survivors who were overweight or obese (n = 220) and who were enrolled in a weight loss intervention study provided baseline and follow-up blood samples and weight data. Serum estrogens, SHBG, insulin, and leptin were measured at baseline, 6 months, and 18 months. RESULTS: Weight loss of ≥5% of initial weight decreased leptin and insulin compared with those who did not achieve that amount of weight loss (P < .0001). Weight loss also increased SHBG at 6 and 18 months (P < .01). Postmenopausal women who lost ≥5% of body weight at 6 months had lower estrone (P = .02), estradiol (P = .002), and bioavailable estradiol (P = .001) concentrations than women who did not lose at least 5% of body weight, and weight loss at 18 months was significantly related to a change in serum bioavailable estradiol concentration (P = .02). CONCLUSIONS: Favorable changes in estrogens, SHBG, insulin, and leptin were observed in association with weight loss in these women who were overweight or obese and who had been diagnosed and treated for breast cancer. Weight loss appears to have favorable effects on hormonal and biologic factors associated with increased risk for recurrence and poorer prognosis.