Improving lifestyle behaviors during chemotherapy for breast cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis (LEANer) Trial.

BACKGROUND: Little is known about improving physical activity (PA) and diet during and after chemotherapy for breast cancer. This secondary analysis examines changes in PA and diet quality during a yearlong intervention for patients with breast cancer undergoing chemotherapy and evaluates factors associated with these changes. METHODS: Newly diagnosed patients with breast cancer (N = 173) undergoing chemotherapy were randomized to a year-long nutrition and exercise intervention (n = 87) or usual care (UC, n = 86). Mixed models compared 1-year changes in PA and diet quality via the Healthy Eating Index (HEI)-2015 by study arm. Among the intervention group, baseline factors associated with change in PA and diet were assessed with multivariable linear and logistic regression. RESULTS: At 1 year, compared with UC, the intervention arm increased PA more (mean difference = 136.1 minutes/week; 95% CI, 90.2-182.0), participated in more strength training (56% vs. 15%; p < .001), and had suggestive improvements in HEI-2015 (mean difference = 2.5; 95% CI, -0.3 to 5.3; p = .08). In the intervention arm, lower fatigue was associated with improved PA (p = .04) and higher education was associated with improved HEI-2015 (p = .001) at 1 year. Higher HEI-2015 (p = .04) and married/living with someone (p = .05) were associated with higher odds of participating in strength training at 1 year. CONCLUSIONS: This year-long lifestyle intervention for patients with breast cancer undergoing chemotherapy resulted in increases in PA and suggestive improvements in diet quality. Behavior change was associated with baseline fatigue, diet quality, education, and married/living with someone. Addressing these factors in interventions may improve uptake of lifestyle behaviors in trials during and after chemotherapy.

Delivery of Cancer Survivorship Education to Community Healthcare Professionals.

Our pilot study aimed to evaluate the needs of community oncology providers with regard to cancer survivorship education, develop a survivorship curriculum based on the needs assessment, and evaluate the acceptability of the Project ECHO® (Extension for Community Healthcare Outcomes) model for delivery of the survivorship curriculum. A needs assessment was delivered to participants in suburban community cancer practices, and a curriculum was developed based on the results. Participants were enrolled in an ECHO curriculum consisting of 6 sessions from October to December 2019. Participants included registered nurses (RN), registered dietitians (RD), clinical social workers (LCSW), advanced practice providers (APP), radiation oncologists, and medical oncologists (MD). Participants were invited to participate in exit interviews designed to better evaluate the participant experience. Ninety percent of needs assessment participants (n = 37) expressed an interest in cancer survivorship education. Eight participants from 3 community practices in suburban Connecticut enrolled in the ECHO curriculum. Four participants (50%) agreed to participate in exit interviews. Five themes emerged from the exit interviews: interest in survivorship, time, positive experience, empowerment, and community. Our Survivorship ECHO pilot demonstrated the acceptability of the Project ECHO® model for delivering cancer survivorship education to oncology providers. Further research confirming the feasibility of this model in additional oncology provider settings is needed.

Examining the effect of obesity-associated gene variants on breast cancer survivors in a randomized weight loss intervention.

PURPOSE: Our study examined whether common variants of obesity-associated genes FTO, MC4R, BDNF, and CREB1 moderated the effects of a lifestyle intervention on weight change among breast cancer survivors. METHODS: 151 breast cancer survivors with a body mass index ≥ 25 kg/m2 were randomly assigned to a 6-month weight loss intervention or usual care group. Genotyping of FTO rs9939609, MC4R rs6567160, BDNF rs11030104, CREB1 rs17203016 was performed. Linear mixed models were used including the main effects of genotype (assuming a dominant genetic model), treatment arm on weight and percent body fat changes, and genotype by treatment interaction variable. All statistical tests were evaluated against a Bonferroni-corrected alpha of 0.0125. RESULTS: Women in the intervention group achieved significantly greater weight loss than the usual care group (5.9% vs 0.4%, p < 0.001), regardless of genotype. Changes in weight and percent body fat did not differ significantly between carriers of the FTO rs9939609, MC4R rs6567160, BDNF rs11030104, and CREB1 rs17203016 risk alleles compared to non-carriers (p-interaction > 0.0125 for each single-nucleotide polymorphisms). CONCLUSIONS: Women who are genetically predisposed to obesity and recently diagnosed with breast cancer may achieve significant and clinically meaningful weight loss through healthy eating and exercise. CLINICAL TRIAL REGISTRATION: NCT02863887 (Date of Registration: August 11, 2016); NCT02110641 (Date of Registration: April 10, 2014).

Randomized trial of exercise on depressive symptomatology and brain derived neurotrophic factor (BDNF) in ovarian cancer survivors: The Women's Activity and Lifestyle Study in Connecticut (WALC).

OBJECTIVES: Depression is one of the most prevalent mental disorders, and rates are higher among cancer survivors than the general population, and higher in ovarian cancer patients compared to cohorts of other cancer survivors. Physical activity has been associated with lower depressive symptoms in cancer survivors, yet no trial has examined this association in women with ovarian cancer. We examined the effect of exercise on depression symptomatology and serum brain derived neurotrophin factor (BDNF) which has been associated with depression, in women with ovarian cancer. METHODS: We conducted a 6-month home-based randomized trial of exercise vs. attention-control (AC) in 144 ovarian cancer survivors. Depressive symptomatology was measured via the Center for Epidemiologic Studies Depression Scale (CES-D). Serum total and free BDNF was measured at baseline and 6-months. Student's t-statistic and mixed-model repeated measures analysis was used to evaluate six-month change between arms in CES-D scores and BDNF. RESULTS: Women were 57.3 ±â€¯8.6 (mean ±â€¯SD) years old, 1.7 ±â€¯1.0 years post-diagnosis with a baseline CES-D score of 11.79 ±â€¯10.21. The majority (55%) were diagnosed with stage III/IV ovarian cancer. CES-D scores decreased in the exercise arm by 2.7 points (95% CI: -4.4, -0.9) or a 21% decrease compared to a 0.3 point decrease (-2.2, 1.5) (3% decrease) in the AC arm (P = 0.05). There was no difference in change in total or free BDNF between the exercise and AC arms. CONCLUSIONS: Ovarian cancer survivors are able to exercise at recommended levels, and exercise was associated with a significant reduction in depressive symptomatology.

Endocrine-related quality of life in a randomized trial of exercise on aromatase inhibitor-induced arthralgias in breast cancer survivors.

BACKGROUND: The objective of this study was to evaluate the role of a 12-month exercise intervention on endocrine-related quality of life (QOL) and overall QOL among breast cancer survivors with aromatase inhibitor (AI)-induced arthralgia in the Hormones and Physical Exercise (HOPE) Study. METHODS: This was a randomized controlled trial of 121 breast cancer survivors who were currently receiving AIs and experiencing at least mild arthralgia. QOL was assessed using the Functional Assessment of Cancer Therapy (FACT) questionnaires and the 36-Item Short Form Survey (SF-36) at baseline, 6 months, and 12 months. Participants were randomized to either a 1-year gym-based, supervised exercise intervention group (150 minutes of aerobic exercise and 2 strength-training sessions each week) or a usual care group. Effects of the intervention on QOL were assessed using mixed-model, repeated-measures analysis. RESULTS: At 12 months, the exercise group had greater improvement in the overall QOL measures as well as the breast cancer-specific (scores, 2.2 vs 0.7; P = .02), endocrine-specific (scores, 5.6 vs 1.6; P < .001), and fatigue-specific (score, 5.8 vs 0.5; P < .001) subscales compared with the usual care group. The results indicated a stronger effect at 12 months versus 6 months after the intervention. CONCLUSIONS: Combined aerobic and resistance exercise, such as treadmill walking and strength training, improved endocrine-related and overall QOL among breast cancer survivors who were experiencing adverse side effects from AIs. Because adverse side effects associated with AI use are quite common and this is the main reason for treatment discontinuation, this nonpharmacologic intervention could benefit many breast cancer survivors and increase successful adherence to AIs in breast cancer treatment.

Lymphedema in ovarian cancer survivors: Assessing diagnostic methods and the effects of physical activity.

BACKGROUND: Lymphedema is a poorly understood side effect of gynecologic cancer treatment. This study was designed to determine the prevalence of lower limb lymphedema (LLL) in a sample of ovarian cancer survivors via 3 different diagnostic methods and to assess the effect of a randomized exercise intervention. METHODS: Physically inactive ovarian cancer survivors (n = 95) were enrolled in a 6-month randomized trial of exercise (primarily brisk walking) versus attention control. LLL was measured at baseline and 6-month visits via a self-report questionnaire, optoelectronic perometry, and an evaluation by a certified lymphedema specialist. RESULTS: LLL prevalence ranged from 21% to 38% according to the diagnostic method, and there was substantial agreement between the self-report questionnaire and the lymphedema specialist evaluation (κ = 0.61). There was no agreement between the evaluation with optoelectronic perometry and the specialist evaluation. With LLL defined by any method, the baseline prevalence was 38% in both groups. At 6 months, both groups experienced a decreased LLL prevalence: 28% in the exercise group and 35% in the control group. There was no difference in the change in lymphedema prevalence between the 2 groups (P = .64). Body mass index was a significant predictor of LLL. CONCLUSIONS: With a potential prevalence of LLL as high as 40%, further evaluation of diagnostic methods is required to better characterize this side effect of ovarian cancer treatment. No adverse effect of exercise on LLL was found. Further research is strongly needed to evaluate predictors of LLL and the effects of exercise on LLL in order to develop effective physical activity recommendations for women with ovarian cancer. Cancer 2018;124:1929-37. © 2018 American Cancer Society.

Exercise and weight loss interventions and miRNA expression in women with breast cancer.

PURPOSE: Obesity and weight gain are associated with comorbidities including a higher risk of tumor recurrence and cancer-related deaths among breast cancer (BC) survivors; however, the underlying mechanisms linking obesity and cancer are poorly understood. Given the lack of clinically validated BC biomarkers, obesity and weight-loss studies utilize serum biomarkers as the intermediary outcomes of tumor recurrence. Studies have indicated microRNAs (miRNA)s are reliable biomarkers for cancer. We hypothesized that miRNA expression correlates with obesity and weight loss amongst BC survivors. This would yield insight into the biological pathways by which this association occurs, enabling more precise development of therapeutics. PATIENTS AND METHODS: We correlated baseline body mass index (BMI) with serum miRNA expression in 121 BC survivors enrolled in the Hormones and Physical Exercise (HOPE) trial. We then analyzed expression of the 35 most abundant miRNAs from HOPE in a six-month randomized controlled weight-loss trial (Lifestyle, Exercise, and Nutrition; LEAN) in 100 BC survivors. Ingenuity pathway analysis (IPA) software was used to identify biological pathway targets of the BMI-associated and intervention-responsive miRNAs using predictive biomarkers. RESULTS: Pearson correlations in HOPE identified eight miRNAs associated with BMI, including miR-191-5p (r = - 0.22, p = 0.016) and miR-122-5p (r = 0.25, p = 0.0048). In the LEAN validation study, levels of miR-191-5p significantly increased during the six-month intervention (p = 0.082). Ingenuity Pathway Analysis identified "Estrogen-mediated S-phase entry" (HOPE p = 0.003; LEAN p < 0.001) and "Molecular mechanisms of cancer" (HOPE p = 0.02; LEAN p < 0.001) as the top canonical pathways that significantly correlated with BMI-associated and intervention-responsive miRNAs and contain obesity and cancer-relevant genes including the E2F family of transcription factors and CCND1, which have been implicated in sporadic BC. CONCLUSION: While the association between obesity and BC recurrence and mortality has been demonstrated in the literature, mechanisms underlying the link between weight gain and cancer are unclear. Using two independent clinical trials, we identified novel miRNAs associative to BMI and weight loss that contribute to the development of cancer. Predictive modeling of miRNA targets identified multiple canonical pathways associated with cancer, highlighting potential mechanisms explaining the link between BMI and increased cancer risk.

Randomized controlled trial of weight loss versus usual care on telomere length in women with breast cancer: the lifestyle, exercise, and nutrition (LEAN) study.

PURPOSE: Some studies suggest that telomere shortening may be associated with increased breast cancer risk and mortality. Obesity is also associated with increased breast cancer risk and mortality. Few studies have examined changes in telomere length in overweight or obese breast cancer survivors. The purpose of our study was to examine the effect of a 6-month diet- and exercise-induced weight loss intervention versus usual care on telomere length in breast cancer survivors. METHODS: 151 breast cancer survivors with body mass index (BMI) ≥ 25 kg/m2 were randomly assigned to a 6-month weight loss intervention (n = 93) or to usual care (n = 58). Fasting blood samples, height, weight, physical activity, and diet were measured at baseline and 6-months. Relative telomere length (RTL) was measured by quantitative-polymerase chain reaction (qPCR) done on buffy coat-extracted genomic DNA. Mean baseline to 6-month changes were compared between groups (intention-to-treat) using generalized estimating equations. RESULTS: Complete telomere data were available in 125 participants. Women were 58 ± 8 years, with BMI 33.0 ± 6.2 kg/m2 and were 2.9 ± 2.5 years from diagnosis; 90% were non-Hispanic white, and 76% had stage 0/I breast cancer. After 6 months, women randomized to weight loss had 3% telomere lengthening compared to 5% shortening in the usual care group (p = 0.12). Among women with stage 0/I, the intervention group experienced 7% telomere lengthening compared to 8% shortening in the usual care group (p = 0.01). No intervention effect was observed in women with stage II/III breast cancer. CONCLUSION: Our findings suggest a weight loss intervention in stage 0 and 1 breast cancer survivors may lead to telomere lengthening, compared to a shortening in their usual care counterparts.

Effect of the LIVESTRONG at the YMCA exercise program on physical activity, fitness, quality of life, and fatigue in cancer survivors.

BACKGROUND: Physical activity (PA) has been linked to a lower risk of developing and dying of cancer, yet many cancer survivors do not exercise. In the current study, the authors evaluated the impact of the LIVESTRONG at the YMCA exercise program, available at Young Men's Christian Associations (YMCAs) across the United States, on PA, fitness, quality of life, fatigue, body composition, serum biomarkers, and program safety in cancer survivors. METHODS: Cancer survivors were recruited through the Yale Cancer Center and the Dana-Farber Cancer Institute and randomized to a 12-week, twice-weekly LIVESTRONG at the YMCA exercise program at YMCAs in Connecticut or Massachusetts or to a control group. Questionnaires, dual-energy x-ray absorptiometry scans, 6-minute walk tests (6MWTs), and a fasting blood draw were completed at baseline and at 12 weeks. Intervention effects were evaluated using mixed model repeated measures analysis, with changes at 12 weeks in PA and 6MWT as the primary endpoints. RESULTS: A total of 186 participants were randomized (95 to the exercise group and 91 to the control group). The majority of patients were diagnosed with AJCC stage I to II cancer and 53% had breast cancer. Participants randomized to the LIVESTRONG at the YMCA program experienced increases in PA (71% exercising at ≥ 150 minutes/week vs 26% of controls; P<.05) and improvements in the 6MWT (group difference: 28.9 meters [95% confidence interval, 0.3-49.0; P = .004]) and quality of life (group difference: 2.6 [95% confidence interval, 0.1-5.0; P = .04]). No adverse events were reported. CONCLUSIONS: The LIVESTRONG at the YMCA exercise program has the potential to impact thousands of survivors across the YMCA network and could lead to improvements in disease and psychosocial outcomes in the growing population of cancer survivors. Cancer 2017;123:1249-1258. © 2016 American Cancer Society.

Effect of exercise on body composition among women with ovarian cancer.

PURPOSE: Obesity is associated with a higher risk of mortality in women with ovarian cancer. Exercise has improved body composition among cancer survivors, yet no randomized controlled trial has explored the effect of exercise on body composition in women with ovarian cancer. In this analysis, we examined the effect of a six-month aerobic exercise intervention on body composition among ovarian cancer survivors in the Women's Activity and Lifestyle Study in Connecticut (WALC). METHODS: Women with ovarian cancer (N = 144) were randomized in a 1:1 ratio to 6 months of an aerobic exercise intervention or attention-control, and body composition was measured as a secondary outcome at baseline and 6 months via dual-energy X-ray absorptiometry (DEXA). Women with at least one DEXA scan were included in the analysis (N = 103). RESULTS: On average, participants were 57.1 (± 8.7) years old and 1.6 (± 0.9) years since diagnosis. Women randomized to exercise maintained weight during the trial (- 0.11 kg, P = 0.82), while women in attention-control gained weight (+ 1.40 kg, P = 0.03); however, the between-group difference did not reach statistical significance (P = 0.09). We found no statistically significant differences by study arm for changes in body fat percentage, bone mineral density, or lean body mass. CONCLUSIONS: Weight was maintained as a result of a 6-month aerobic exercise intervention among post-treatment ovarian cancer survivors. Future exercise and healthy eating interventions should consider additional measures (e.g., computer tomography scans, D3-creatinine) to more accurately assess changes in body composition. IMPLICATIONS FOR CANCER SURVIVORS: Moderate-intensity aerobic exercise may help ovarian cancer survivors maintain weight.

Effect of Exercise on Chemotherapy-Induced Peripheral Neuropathy Among Patients Treated for Ovarian Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Chemotherapy-induced peripheral neuropathy (CIPN), one of the most common and severe adverse effects of chemotherapy, is associated with worse quality of life among survivors of ovarian cancer. Currently, there is no effective treatment for CIPN. Objective: To evaluate the effect of a 6-month aerobic exercise intervention vs attention-control on CIPN among women treated for ovarian cancer in the Women's Activity and Lifestyle Study in Connecticut (WALC) to provide evidence to inform the guidelines and recommendations for prevention or treatment of CIPN. Design, Setting, and Participants: This prespecified secondary analysis evaluated the Women's Activity and Lifestyle Study in Connecticut (WALC), a multicentered, open-label, population-based, phase 3 randomized clinical trial of an aerobic exercise intervention vs attention control for CIPN in patients who were diagnosed with ovarian cancer. Only WALC participants who received chemotherapy were included in this analysis. Participants were randomized 1:1 to either a 6-month aerobic exercise intervention or to attention control. All analyses were conducted between September 2022 and January 2023. Interventions: The exercise intervention consisted of home-based moderate-intensity aerobic exercise facilitated by weekly telephone counseling from an American College of Sports Medicine/American Cancer Society-certified cancer exercise trainer. Attention control involved weekly health education telephone calls from a WALC staff member. Main Outcomes and Measure: Change in CIPN was the primary outcome in this secondary analysis. This outcome was represented by CIPN severity, which was self-measured by participants at baseline and 6 months using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale, with a score range of 0 to 44. A mixed-effects model was used to assess the 6-month change in CIPN between the exercise intervention and attention control arms. Results: Of the 134 participants (all females; mean [SD] age, 57.5 [8.3] years) included in the analysis, 69 were in the exercise intervention arm and 65 were in the attention control arm. The mean (SD) time since diagnosis was 1.7 (1.0) years. The mean (SD) baseline CIPN scores were 8.1 (5.6) in the exercise intervention arm and 8.8 (7.9) in the attention control arm (P = .56). At 6 months, the self-reported CIPN score was reduced by 1.3 (95% CI, -2.3 to -0.2) points in the exercise intervention arm compared with an increase of 0.4 (95% CI, -0.8 to 1.5) points in the attention control arm. The between-group difference was -1.6 (95% CI, -3.1 to -0.2) points. The point estimate was larger among the 127 patients with CIPN symptoms at enrollment (-2.0; 95% CI, -3.6 to -0.5 points). Conclusions and Relevance: Findings of this secondary analysis of the WALC trial indicate that a 6-month aerobic exercise intervention vs attention control significantly improved self-reported CIPN among patients who were treated for ovarian cancer. While replication of the findings in other studies is warranted, incorporating referrals to exercise programs into standard oncology care could reduce CIPN symptoms and increase quality of life in patients with ovarian cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02107066.

Exercise adherence in a randomized controlled trial of exercise on quality of life in ovarian cancer survivors.

PURPOSE: Factors associated with improving exercise in ovarian cancer survivors remain unknown. We explored characteristics associated with exercise adherence among women treated for ovarian cancer in the Women's Activity and Lifestyle Study in Connecticut (WALC) randomized controlled trial. METHODS: We evaluated adherence among women randomized to the WALC exercise intervention (N = 74). Women had to be exercising ≤ 90 min/week and post-treatment. The intervention included 25 telephone-based exercise counseling sessions over 6 months. Adherence was defined as 150 min/week of moderate/vigorous-intensity exercise. We evaluated factors associated with exercise adherence and duration using multivariate logistic and linear regression. The number of sessions sufficient to achieve 150 min/week was modeled with an unadjusted receiver operating characteristic (ROC) curve. RESULTS: Women were 57.3 ± 8.8 years old and 1.7 ± 1.0 years since diagnosis. The mean exercise time over 6 months was 166.0 ± 66.1 min/week, and 64.9% of women met the 150 min/week goal. Women attended 22.8 ± 3.6 (92%) counseling sessions. No cancer recurrence during the study (OR = 9.15, 95% CI: 1.09-44.02) and greater session attendance (OR = 1.21, 95% CI: 1.02-1.43) were related to meeting the exercise goal. Greater session attendance (P < 0.01) and higher baseline activity level (P = 0.02) were associated with greater average weekly exercise duration. The ROC curve suggested attending 18 counseling sessions was optimal to meet the exercise goal. CONCLUSIONS: Women attending more counseling sessions or with no cancer recurrence during the study were more likely to meet the exercise goal. More research is needed to understand ideal counseling intensity for ovarian cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Eighteen counseling sessions are sufficient for ovarian cancer survivors to achieve 150 min/week exercise.

Randomized trial of exercise on cancer-related blood biomarkers and survival in women with ovarian cancer.

BACKGROUND: In randomized trials in women with breast cancer, exercise has been shown to have beneficial effects on cancer-related circulating biomarkers that may impact survival. Such studies are lacking for ovarian cancer. METHODS: This secondary analysis of a published randomized controlled trial examined the impact of a 6-month exercise intervention versus attention-control on change in prespecified circulating biomarkers (cancer antigen 125 (CA-125), C-reactive protein (CRP), insulin-like growth factor-1(IGF-1), insulin and leptin) in a subset of participants who provided a fasting blood draw (N = 104/144) at enrollment and at 6 months. Change in biomarkers between study arms was compared using a linear mixed effects model analysis. An exploratory analysis of the exercise intervention versus attention-control on all-cause mortality included all (N = 144) participants. All statistical tests were two-sided. RESULTS: Participants included in the biomarker analysis were 57.0 ± 8.8 (mean ± SD) years old and 1.6 ± 0.9 years post-diagnosis. Adherence to the exercise intervention was 176.4 ± 63.5 min/week. Post intervention IGF-1 (group difference in change: -14.2 (-26.1 to -2.3) ng/mL (least squared means (95% CI))) and leptin (-8.9 (-16.5 to -1.4) ng/mL) were significantly reduced in the exercise group (N = 53) compared to those in attention-control (N = 51). No group difference in change was seen for CA-125 (p = 0.54), CRP (p = 0.95), or insulin (p = 0.37). With median follow-up of 70 months [range 6.6-105.4 months], 50/144 (34.7%) (exercise group; 24/74 (32.4%) versus attention-control group; 26/70 (37.1%)) participants died with no between group difference in overall survival (p = 0.99). CONCLUSIONS: Further studies are needed to determine the clinical significance of exercise-induced changes in cancer-related circulating biomarkers in women with ovarian cancer.

Diet and physical activity interventions in Black and Latina women with breast cancer: A scoping review.

Background: A growing number of lifestyle interventions are being developed to promote weight loss and adoption of a healthful lifestyles among breast cancer survivors; yet Black and Latina women remain underrepresented. Purpose: We performed a scoping review of the available peer-reviewed literature to describe and compare the content, design, methods, and primary outcomes of current diet and/or physical activity (PA) interventions after a breast cancer diagnosis among Black and Latina women. Methods: We queried PubMed, EMBASE, CINAHL, MEDLINE, and Clinicaltrials.gov up to October 1, 2022, to identify all randomized controlled trials of diet and/or PA after diagnosis of breast cancer with a majority (>50%) of Black or Latina participants. Results: Twenty-two randomized controlled trials were included in this review (five efficacy, twelve pilot, five on-going). Nine trials were among Latinas (two diet, four PA, and three diet/PA), six among Blacks (one PA and five diet/PA) and seven included both populations (five PA and two diet/PA), all of which examined different endpoints. Two of the five efficacy studies achieved their a priori outcome (one diet trial improved short term dietary intake; one PA trial achieved clinically significant improvements in metabolic syndrome score), both in Latinas. Eight pilot trials intervened on both diet and PA and three of them found favorable behavioral changes. Three (two for Latinas and one for Blacks) out of the nine diet and PA trials and three (all for Latinas) efficacy trials incorporated a culturally focused approach (i.e., traditional foods, music, Spanish content, bicultural health coaches, spirituality). Overall, four trials, including one efficacy trial, had one-year follow-up data, with three finding sustained behavior change. Electronic/mobile components were incorporated in five trials and one involved informal care givers. Most of the trials were geographically limited to the Northeast USA (n=8, NY, NC, DC, NJ) and Texas (n=4). Conclusions: Most of the trials we identified were pilot or feasibility studies and of short duration, demonstrating the need for large randomized controlled efficacy lifestyle interventions among Black and Latina breast cancer survivors. Culturally tailored programing was limited but is an important component to incorporate in future trials in these populations.

Randomized Trial Evaluating a Self-Guided Lifestyle Intervention Delivered via Evidence-Based Materials versus a Waitlist Group on Changes in Body Weight, Diet Quality, Physical Activity, and Quality of Life among Breast Cancer Survivors.

Background: Lifestyle interventions for breast cancer survivors have proved effective at stimulating positive behavior change and promoting healthy weight loss, although integrating these programs into clinical practice is challenging. We evaluated the effect of a 6-month, unsupervised, self-guided, lifestyle intervention using printed materials and online videos vs. waitlist group on body weight for breast cancer survivors. Methods: The Lifestyle, Exercise and Nutrition (LEAN) Self-Guided trial randomized breast cancer survivors with a body mass index ≥25 kg/m2 to a 6-month lifestyle intervention (N = 102) or waitlist group (N = 103). Effects of the intervention on self-reported body weight, physical activity (PA), diet quality (via Health Eating Index-2010 (HEI-2010)), and quality of life were assessed using mixed model repeated measures analysis. Results: At 6 months, the intervention arm had significantly greater weight loss compared with the waitlist group (mean difference = -1.3 kg, 95% confidence interval [CI] = -2.5, -0.13). We observed suggestive improvements in PA (mean difference = 18.7 min/week, 95% CI = -24.2, 61.6), diet quality (mean difference in HEI = 3.2 points, 95% CI = -0.20, 6.5), and fatigue (mean difference in Functional Assessment of Chronic Illness Therapy-Fatigue scale = 1.4 points, 95% CI = -1.1, 3.9). Conclusions: The LEAN Self-Guided intervention led to favorable weight changes over 6 months. Low-resource-intensive programs have the potential to be delivered in diverse healthcare settings and may support breast cancer survivors in achieving a healthy body weight.

Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study.

PURPOSE: Successful completion of chemotherapy is critical to improve breast cancer outcomes. Relative dose intensity (RDI), defined as the ratio of chemotherapy delivered to prescribed, is a measure of chemotherapy completion and is associated with cancer mortality. The effect of exercise and eating a healthy diet on RDI is unknown. We conducted a randomized trial of an exercise and nutrition intervention on RDI and pathologic complete response (pCR) in women diagnosed with breast cancer initiating chemotherapy. METHODS: One hundred seventy-three women with stage I-III breast cancer were randomly assigned to usual care (UC; n = 86) or a home-based exercise and nutrition intervention with counseling sessions delivered by oncology-certified registered dietitians (n = 87). Chemotherapy dose adjustments and delays and pCR were abstracted from electronic medical records. T-tests and chi-square tests were used to examine the effect of the intervention versus UC on RDI and pCR. RESULTS: Participants randomly assigned to intervention had greater improvements in exercise and diet quality compared with UC (P < .05). RDI was 92.9% ± 12.1% and 93.6% ± 11.1% for intervention and UC, respectively (P = .69); the proportion of patients in the intervention versus UC who achieved ≥85% RDI was 81% and 85%, respectively (P = .44). The proportion of patients who had at least one dose reduction and/or delay was 38% intervention and 36% UC (P = .80). Among 72 women who received neoadjuvant chemotherapy, women randomly assigned to intervention were more likely to have a pCR than those randomly assigned to UC (53% v 28%; P = .037). CONCLUSION: Although a diet and exercise intervention did not affect RDI, the intervention was associated with a higher pCR in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative and triple-negative breast cancer undergoing neoadjuvant chemotherapy.

Impact of a randomized weight loss trial on breast tissue markers in breast cancer survivors.

Few trials have examined the effect of lifestyle behavioral interventions on tissue markers in patients with cancer. The purpose of this study was to examine the feasibility and impact of a 6-month weight loss intervention on breast tissue and serum biomarkers in women with breast cancer. Fifty-one women who completed breast cancer treatment and had a BMI ≥ 25.0 kg/m2 were randomized to a weight loss intervention or usual care. Breast tissue biopsies, fasting blood draw and body composition were collected at baseline and 6 months, with between-group changes examined using analysis of covariance method. Baseline and post-intervention biopsies were conducted in 49 and 42 women, respectively, with pre- and post-epithelial tissue available from 25 tissue samples. Average 6-month weight loss was 6.7% for the weight loss group and 2.0% increase for the usual care group (p < 0.0001). At baseline, body fat and serum insulin levels were inversely associated with breast tissue insulin receptor levels and CD68 (p < 0.05). At 6 months, favorable changes were observed in serum leptin and adiponectin levels and tissue CD163 among women randomized to weight loss vs. adverse change in women randomized to usual care (p < 0.05). Breast tissue biopsies are feasible to collect in a clinical research setting among breast cancer survivors, with weight loss favorably impacting metabolic and inflammatory markers associated with breast cancer.

Effect of the Lifestyle, Exercise, and Nutrition (LEAN) Study on Long-Term Weight Loss Maintenance in Women with Breast Cancer.

Lifestyle interventions among breast cancer survivors with obesity have demonstrated successful short-term weight loss, but data on long-term weight maintenance are limited. We evaluated long-term weight loss maintenance in 100 breast cancer survivors with overweight/obesity in the efficacious six-month Lifestyle, Exercise, and Nutrition (LEAN) Study (intervention = 67; usual care = 33). Measured baseline and six-month weights were available for 92 women. Long-term weight data were obtained from electronic health records. We assessed weight trajectories between study completion (2012-2013) and July 2019 using growth curve analyses. Over up to eight years (mean = 5.9, SD = 1.9) of post-intervention follow-up, both the intervention (n = 60) and usual care (n = 32) groups declined in body weight. Controlling for body weight at study completion, the yearly weight loss rate in the intervention and usual care groups was -0.20 kg (-0.2%/year) (95% CI: 0.06, 0.33, p = 0.004) and -0.32 kg (-0.4%/year) (95% CI: 0.12, 0.53, p = 0.002), respectively; mean weight change did not differ between groups (p = 0.31). It was encouraging that both groups maintained their original intervention period weight loss (6% intervention, 2% usual care) and had modest weight loss during long-term follow-up. Breast cancer survivors in the LEAN Study, regardless of randomization, avoided long-term weight gain following study completion.

Dietary Supplement Use and Interactions with Tamoxifen and Aromatase Inhibitors in Breast Cancer Survivors Enrolled in Lifestyle Interventions.

The use of dietary supplements is common in the general population and even more prevalent among cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research specifies that dietary supplements should not be used for cancer prevention. Several dietary supplements have potential pharmacokinetic and pharmacodynamic interactions that may change their clinical efficacy or potentiate adverse effects of the adjuvant endocrine therapy prescribed for breast cancer treatment. This analysis examined the prevalence of self-reported dietary supplement use and the potential interactions with tamoxifen and aromatase inhibitors (AIs) among breast cancer survivors enrolled in three randomized controlled trials of lifestyle interventions conducted between 2010 and 2017. The potential interactions with tamoxifen and AIs were identified using the Natural Medicine Database. Among 475 breast cancer survivors (2.9 (mean) or 2.5 (standard deviation) years from diagnosis), 393 (83%) reported using dietary supplements. A total of 108 different types of dietary supplements were reported and 36 potential adverse interactions with tamoxifen or AIs were identified. Among the 353 women taking tamoxifen or AIs, 38% were taking dietary supplements with a potential risk of interactions. We observed a high prevalence of dietary supplement use among breast cancer survivors and the potential for adverse interactions between the prescribed endocrine therapy and dietary supplements was common.

Randomized trial of weight loss on circulating ghrelin levels among breast cancer survivors.

Obesity among breast cancer survivors is associated with increased risk for recurrence and mortality. The hormone ghrelin plays a role in initiating appetite and thus regulating body weight. This study aims to determine the effect of a lifestyle intervention on ghrelin levels in breast cancer survivors with a body mass index (BMI) ≥ 25 kg/m2. The Lifestyle, Exercise, and Nutrition (LEAN) study was a 6-month randomized trial, examining the effectiveness of a weight loss intervention versus usual care in 151 breast cancer survivors with BMI ≥ 25 kg/m2. Ghrelin was measured in fasting baseline and 6-month blood samples. Baseline associations between ghrelin, body composition, and blood biomarkers were examined. Six-month change in ghrelin was compared between study arms. Ghrelin measurements were available for 149 women. At baseline, ghrelin was correlated with age (r = 0.28, p < 0.001) and inversely correlated with weight (r = -0.18, p = 0.03), lean body mass (r = -0.18, p = 0.02), and leptin (r = -0.18, p = 0.03). Over 6 months, ghrelin increased by 144 pg/mL (7.2%) in the intervention and decreased by 466 pg/mL (32.5%) in the usual care (p = 0.07). Among all women, greater weight loss was associated with an increase in ghrelin (p = 0.01). These findings indicate that weight loss, achieved through a lifestyle intervention, is associated with higher ghrelin levels in breast cancer survivors which may be informative for developing sustainable weight loss programming for this population. Future research should investigate the long term impacts of lifestyle interventions on ghrelin levels in the context of weight maintenance and weight regain.