Translating energy balance research from the bench to the clinic to the community: Parallel animal-human studies in cancer.

Advances in energy balance and cancer research to date have largely occurred in siloed work in rodents or patients. However, substantial benefit can be derived from parallel studies in which animal models inform the design of clinical and population studies or in which clinical observations become the basis for animal studies. The conference Translating Energy Balance from Bench to Communities: Application of Parallel Animal-Human Studies in Cancer, held in July 2021, convened investigators from basic, translational/clinical, and population science research to share knowledge, examples of successful parallel studies, and strong research to move the field of energy balance and cancer toward practice changes. This review summarizes key topics discussed to advance research on the role of energy balance, including physical activity, body composition, and dietary intake, on cancer development, cancer outcomes, and healthy survivorship.

Weight management and physical activity throughout the cancer care continuum.

Mounting evidence suggests that weight management and physical activity (PA) improve overall health and well being, and reduce the risk of morbidity and mortality among cancer survivors. Although many opportunities exist to include weight management and PA in routine cancer care, several barriers remain. This review summarizes key topics addressed in a recent National Academies of Science, Engineering, and Medicine workshop entitled, "Incorporating Weight Management and Physical Activity Throughout the Cancer Care Continuum." Discussions related to body weight and PA among cancer survivors included: 1) current knowledge and gaps related to health outcomes; 2) effective intervention approaches; 3) addressing the needs of diverse populations of cancer survivors; 4) opportunities and challenges of workforce, care coordination, and technologies for program implementation; 5) models of care; and 6) program coverage. While more discoveries are still needed for the provision of optimal weight-management and PA programs for cancer survivors, obesity and inactivity currently jeopardize their overall health and quality of life. Actionable future directions are presented for research; practice and policy changes required to assure the availability of effective, affordable, and feasible weight management; and PA services for all cancer survivors as a part of their routine cancer care. CA Cancer J Clin 2018;68:64-89. © 2017 American Cancer Society.

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.

Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study.

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.

A qualitative study identifying challenges resulting from complex evidence on lifestyle factors and cancer: perspectives from Black and Latina cancer survivors and healthcare providers.

PURPOSE: Most breast cancer survivors have challenges with adopting healthy lifestyle behaviors. This may be due to contextual challenges that result from the complex nature of the evidence. To address this gap, we explored the experiences of breast cancer survivors of color and oncology healthcare providers. METHODS: Content analysis with inductive and deductive approaches was used for semi-structured interviews with 26 female breast cancer survivors and 10 oncology healthcare providers from Greater New Haven, Connecticut. RESULTS: Survivors identified substantial confusion on the evidence regarding lifestyle behaviors and breast cancer, stemming from inadequate healthcare provider counseling and an overreliance on informal sources of information. Providers identified lack of evidence-based knowledge as a barrier to counseling on these topics. There was a mixed perspective regarding the consistency of evidence, stemming from a combination of gaps in the available evidence and accessing evidence-based knowledge from a wide range of professional resources. Some providers perceived the guidelines as consistent; others felt guidelines were constantly changing, impacting how and on what they counseled. Therefore, many healthcare providers in oncology care relied on generic messaging on lifestyle behaviors after a cancer diagnosis. CONCLUSIONS: Inconsistent information sources, the rapidly changing evidence, and gaps in the current evidence contribute to generic messaging about lifestyle behaviors and may inhibit a survivor's ability to engage in behavior change. Consistent and uniform healthy lifestyle guidelines for cancer outcomes may address both provider and patient level barriers to knowledge.

Exploring anxiety as an influencing factor of the impact of exercise and mind-body prehabilitation on cognitive functioning among women undergoing breast cancer surgery.

OBJECTIVE: The purpose of this secondary analysis was to describe the prevalence of anxiety, depression, and perceived stress among women newly diagnosed with breast cancer and the impact of baseline and changes in anxiety on cognitive functioning following exercise and mind-body prehabilitation interventions. METHODS: The sample consisted of 49 women with newly diagnosed breast cancer (stages I-III) who planned to undergo breast cancer surgery at two academic cancer centers. Participants were randomized to receive an exercise or mind-body prehabilitation intervention between the time of diagnosis and breast cancer surgery. Participants completed self-report measures of anxiety, depression (HADS), perceived stress, and cognitive functioning (EORTC-QLQ-C30) at study enrollment and prior to surgery (post-intervention). The relationships between change in cognitive functioning and change in anxiety among all participants were estimated using linear regression modeling. RESULTS: A significant proportion of women with newly diagnosed breast cancer had clinically significant anxiety (34.0%). Greater anxiety was moderately associated with worse cognitive functioning (r = -0.33) at baseline. Linear modeling found that changes in cognitive functioning and anxiety were inversely related: Each one-unit decrease in anxiety was associated with a two-unit improvement in cognitive function (p = .06). CONCLUSIONS: Anxiety was common in women with newly diagnosed breast cancer and was related to worse cognitive functioning. Assessment of anxiety at the time of diagnosis may allow for earlier anxiety management and subsequent improvement in cognitive functioning.

A competing risk analysis of adherence to the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and obesity-related cancer risk in Hispanic/Latino adults in the NIH-AARP Diet and Health Study.

Incidence of obesity-related cancers (ORCs) is rising among US Hispanic/Latino adults, which may be partly due to inadequate engagement in healthy lifestyle behaviors. Prior research on cancer prevention guideline adherence and cancer risk has not considered competing events that may lead to misinterpreting the magnitude of risk between guideline adherence and cancer incidence. Among Hispanic/Latino adults (N = 9204) in the NIH-AARP Diet and Health Study, we examined the association between adherence to the 2012 American Cancer Society (ACS) guidelines (high, moderate, low) on nutrition and physical activity for cancer prevention and risk of any first observed ORC using Fine and Gray methods for competing risk analysis. Over a median of 10.5 years of follow-up, there were 619 first ORCs. The cumulative risk of ORC over a 15-year period was not significantly different across ACS guideline adherence categories (high cumulative incidence function [CIF]: 2.2%-5.8%; moderate CIF: 2.2%-6.6%; low CIF: 2.3%-6.7%, PGray's log rank  = .690). In competing risk analysis, high (compared to low) adherence to the ACS guidelines was associated with reduced probability of ORC (subdistribution hazard [SHR]: 0.76, 95% CI: 0.58-0.996, P = .047), with evidence of a linear trend for increasing adherence (Ptrend  = .039). Our findings were consistent with hypothesized inverse associations between ACS guideline adherence and ORC incidence accounting for competing risks. These findings suggest a need for continued public health efforts focused on promoting engagement in healthy lifestyle behaviors to reduce ORC incidence among US Hispanic/Latino adults.

Adherence to the American Cancer Society Guidelines on nutrition and physical activity for cancer prevention and obesity-related cancer risk and mortality in Black and Latina Women's Health Initiative participants.

BACKGROUND: Although adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention associates with lower risk of obesity-related cancer (ORC) incidence and mortality, evidence in Black and Latina women is limited. This association was examined in Black and Latina participants in the Women's Health Initiative (WHI). METHODS: Semi-Markov multistate model examined the association between ACS guideline adherence and ORC incidence and mortality in the presence of competing events, combined and separately, for 9301 Black and 4221 Latina postmenopausal women. Additionally, ACS guideline adherence was examined in a subset of less common ORCs and potential effect modification by neighborhood socioeconomic status and smoking. RESULTS: Over a median of 11.1, 12.5, and 3.7 years of follow-up for incidence, nonconditional mortality, and conditional mortality, respectively, 1191 ORCs (Black/Latina women: 841/269), 1970 all-cause deaths (Black/Latina women: 1576/394), and 341 ORC-related deaths (Black/Latina women: 259/82) were observed. Higher ACS guideline adherence was associated with lower ORC incidence for both Black (cause-specific hazard ratio [CSHR]highvs.low : 0.72; 95% CI, 0.55-0.94) and Latina (CSHRhighvs.low : 0.58, 95% CI, 0.36-0.93) women; but not conditional all-cause mortality (Black hazard ratio [HR]highvs.low : 0.86; 95% CI, 0.53-1.39; Latina HRhighvs.low : 0.81; 95% CI, 0.32-2.06). Higher adherence was associated with lower incidence of less common ORC (Ptrend  = .025), but conditional mortality events were limited. Adherence and ORC-specific deaths were not associated and there was no evidence of effect modification. CONCLUSIONS: Adherence to the ACS guidelines was associated with lower risk of ORCs and less common ORCs but was not for conditional ORC-related mortality. LAY SUMMARY: Evidence on the association between the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and cancer remains scarce for women of color. Adherence to the guidelines and risk of developing one of 13 obesity-related cancers among Black and Latina women in the Women's Health Initiative was examined. Women who followed the lifestyle guidelines had 28% to 42% lower risk of obesity-related cancer. These findings support public health interventions to reduce growing racial/ethnic disparities in obesity-related cancers.

Marital Status, Living Arrangement, and Cancer Recurrence and Survival in Patients with Stage III Colon Cancer: Findings from CALGB 89803 (Alliance).

BACKGROUND: Limited and conflicting findings have been reported regarding the association between social support and colorectal cancer (CRC) outcomes. We sought to assess the influences of marital status and living arrangement on survival outcomes among patients with stage III colon cancer. PATIENTS AND METHODS: We conducted a secondary analysis of 1082 patients with stage III colon cancer prospectively followed in the CALGB 89803 randomized adjuvant chemotherapy trial. Marital status and living arrangement were both self-reported at the time of enrollment as, respectively, married, divorced, separated, widowed, or never-married, and living alone, with a spouse or partner, with other family, in a nursing home, or other. RESULTS: Over a median follow-up of 7.6 years, divorced/separated/widowed patients experienced worse outcomes relative to those married regarding disease free-survival (DFS) (hazards ratio (HR), 1.44 (95% CI, 1.14-1.81); P =.002), recurrence-free survival (RFS) (HR, 1.35 (95% CI, 1.05-1.73); P = .02), and overall survival (OS) (HR, 1.40 (95% CI, 1.08-1.82); P =.01); outcomes were not significantly different for never-married patients. Compared to patients living with a spouse/partner, those living with other family experienced a DFS of 1.47 (95% CI, 1.02-2.11; P = .04), RFS of 1.34 (95% CI, 0.91-1.98; P = .14), and OS of 1.50 (95% CI, 1.00-2.25; P =.05); patients living alone did not experience significantly different outcomes. CONCLUSION: Among patients with stage III colon cancer who received uniform treatment and follow-up within a nationwide randomized clinical trial, being divorced/separated/widowed and living with other family were significantly associated with greater colon cancer mortality. Interventions enhancing social support services may be clinically relevant for this patient population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00003835.

Exploring the impact of exercise and mind-body prehabilitation interventions on physical and psychological outcomes in women undergoing breast cancer surgery.

PURPOSE: To compare the impact of exercise and mind-body prehabilitation interventions on changes in quality of life and cancer treatment-related symptoms in women with newly diagnosed breast cancer. METHODS: The following describes a secondary analysis of a randomized window of opportunity trial (The Pre-Operative Health and Body Study). Forty-nine women were randomized to participate in either an exercise prehabilitation intervention or a mind-body prehabilitation intervention from the time of enrollment to surgery. Participants (N = 47) completed measures of quality of life, anxiety, depression, and stress at the time of enrollment (T1), post-intervention/surgery (T2), and one-month post-surgery (T3). Changes in outcome measures between groups were compared over time using longitudinal models. RESULTS: Mind-body group participants experienced significant improvements in cognitive functioning in comparison to exercise group participants between T1 and T3 (difference in average change: -9.61, p = 0.04, d = 0.31), otherwise, there were no significant differences between groups. Within group comparisons demonstrated that both groups experienced improvements in anxiety (exercise: average change = -1.18, p = 0.03, d = 0.34; mind-body: average change = -1.69, p = 0.006, d = 0.43) and stress (exercise: average change = -2.33, p = 0.04, d = 0.30; mind-body: average change = -2.59, p = 0.05, d = 0.29), while mind-body group participants experienced improvements in insomnia (average change = -10.03, p = 0.04, d = 0.30) and cognitive functioning (average change = 13.16, p = 0.0003, d = 0.67). CONCLUSIONS: Both prehabilitation interventions impacted cancer treatment-related symptoms. Further work in larger groups of patients is needed to evaluate the efficacy of prehabilitation interventions on quality of life in women with breast cancer. Pre-operative exercise and mind-body interventions may impact physical and/or psychological effects of cancer diagnosis and treatment in women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01516190. Registered January 24, 2012.

Cardiometabolic risk factors, physical activity, and postmenopausal breast cancer mortality: results from the Women's Health Initiative.

BACKGROUND: Higher physical activity levels are associated with lower breast cancer-specific mortality. In addition, the metabolic syndrome is associated with higher breast cancer-specific mortality. Whether the physical activity association with breast cancer mortality is modified by number of metabolic syndrome components (cardiometabolic risk factors) in postmenopausal women with early-stage breast cancer remains unknown. METHODS: Cardiovascular risk factors included high waist circumference, hypertension, high cholesterol, and diabetes. Breast cancers were verified by medical record review. Mortality finding were enhanced by serial National Death Index queries. Cox proportional hazards regression models were used to estimate associations between baseline physical activity and subsequent breast cancer-specific and overall mortality following breast cancer diagnosis in Women's Health Initiative participants. These associations were examined after stratifying by cardiometabolic risk factor group. RESULTS: Among 161,308 Women's Health Initiative (WHI) participants, 8543 breast cancers occurred after 9.5 years (median) follow-up in women, additionally with information on cardiometabolic risk factors and physical activity at entry. In multi-variable analyses, as measured from cancer diagnosis, higher physical activity levels were associated with lower all-cause mortality risk (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.78-0.95, trend P < 0.001) but not with breast cancer-specific mortality (HR 0.85, 95% CI 0.70 to 1.04, trend P = 0.09). The physical activity and all-cause mortality association was not significantly modified by cardiometabolic risk factor number. CONCLUSIONS: Among women with early-stage breast cancer, although higher antecedent physical activity was associated with lower risk of all-cause mortality, the association did not differ by cardiometabolic risk factor number.

Prediagnosis and postdiagnosis leisure time physical activity and survival following diagnosis with ovarian cancer.

Little is known about the influence of prediagnosis and postdiagnosis physical activity on ovarian cancer survival. We investigated this association in two large cohorts, the Nurses' Health Study (NHS) and NHSII. Analyses included 1461 women with confirmed invasive, epithelial ovarian cancer and data on physical activity. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for ovarian cancer-specific mortality. Ovarian cancer-specific mortality was not associated with physical activity reported 1-8 years before diagnosis overall (≥7.5 vs <1.5 MET-hours/week, HR = 0.96), for high-grade serous/ poorly differentiated tumors, or non-serous/ low-grade serous tumors (P-heterogeneity = .45). An inverse association was observed for activity 1-4 years after diagnosis (≥7.5 vs <1.5 MET-hours/week, HR = 0.67, 95%CI: 0.48-0.94), with similar results by histotype (P-heterogeneity = .53). Women who decreased their activity from ≥7.5 MET-hours/week 1-8 years before diagnosis to <7.5 MET-hours/week 1-4 years after diagnosis, compared to those with <7.5 MET-hours/week across periods, had a 49% increased risk of death (HR = 1.49, 95%CI: 1.07-2.08). Physical activity after, but not before, ovarian cancer diagnosis was associated with better prognosis.

Association of relative dose intensity with BMI and pathologic complete response in patients treated with neoadjuvant chemotherapy for breast cancer.

PURPOSE: Previous work found that lower BMI is associated with a pathologic complete response (pCR) following neoadjuvant chemotherapy for breast cancer. Relative dose intensity (RDI) of chemotherapy is an important marker of treatment tolerability. We hypothesized that patients with low BMI would have higher RDI than patients with high BMI, explaining the mechanism for the association between BMI and pCR. METHODS: We conducted a retrospective study of women treated with neoadjuvant chemotherapy for stage I-III breast cancer at Yale New Haven Hospital-Smilow Cancer Hospital. We reviewed medical records to determine tumor characteristics, chemotherapy doses, and reasons for dose reductions or delays. The treatment RDI was calculated using published methods. Chi-squared analyses were conducted to determine the associations between RDI and BMI and between RDI and pCR. RESULTS: Our cohort (n = 237) had an average age of 53 years (SD 13) and mean BMI of 29.5 kg/m2 (SD 7.0). Fifty-eight patients (24%) received <85% RDI, and 61% of patients experienced at least one dose reduction or delay. BMI was not associated with RDI (p = 0.71), and RDI was not associated with pCR (p = 0.31); however, fewer dose delays was associated with pCR (p = 0.02). The most common reasons for dose reduction or delays were neuropathy, myelosuppression, and personal reasons. CONCLUSIONS: Nearly one quarter of our cohort had RDI <85%. Although RDI overall was not associated with pCR, having fewer dose delays was associated with pCR. Our results highlight a need for improved patient adherence to and tolerability of neoadjuvant chemotherapy to minimize treatment delays.

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 physical activity on quality of life and lung cancer biomarkers in patients with advanced stage lung cancer: a pilot study".

BACKGROUND: Lung cancer survivors need more options to improve quality of life (QoL). It is unclear to what extent patients with advanced stage disease are willing to participate in home-based physical activity (PA) and if these interventions improve QoL. The goal of our study was to determine interest in participating in our 3-month home-based walking regimen in patients with advanced stage lung cancer. We used a randomized design to evaluate for potential benefit in PA and patient-reported outcomes. METHODS: We performed an open-label, 1:1 randomized trial in 40 patients with stage III/IV non-small cell lung cancer (NSCLC) evaluating enrollment rate, PA, QoL, dyspnea, depression, and biomarkers. Compared to usual care (UC), the intervention group (IG) received an accelerometer, in-person teaching session, and gain-framed text messages for 12 weeks. RESULTS: We enrolled 56% (40/71) of eligible patients. Participants were on average 65 years and enrolled 1.9 years from diagnosis. Most patients were women (75%), and receiving treatment (85%) for stage IV (73%) adenocarcinoma (83%). A minority of patients were employed part-time or full time (38%). Both groups reported low baseline PA (IG mean 37 (Standard deviation (SD) 46) vs UC 59 (SD 56) minutes/week; p = 0.25). The IG increased PA more than UC (mean change IG + 123 (SD 212) vs UC + 35 (SD 103) minutes/week; p = 0.051)). Step count in the IG was not statistically different between baseline (4707 step/day), week 6 (5605; p = 0.16), and week 12 (4606 steps/day; p = 0.87). The intervention improved EORTC role functioning domain (17 points; p = 0.022) with borderline improvement in dyspnea (- 13 points; p = 0.051) compared to UC. In patients with two blood samples (25%), we observed a significant increase in soluble PD-1 (219.8 (SD 54.5) pg/mL; p < 0.001). CONCLUSIONS: Our pilot trial using a 3-month, home-based, mobile health intervention enrolled over half of eligible patients with stage III and IV NSCLC. The intervention increased PA, and may improve several aspects of QoL. We also identified potential biomarker changes relevant to lung cancer biology. Future research should use a larger sample to examine the effect of exercise on cancer biomarkers, which may mediate the association between PA and QoL. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov ( NCT03352245 ).

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.

Risk factors for hepatocellular carcinoma (HCC) in the northeast of the United States: results of a case-control study.

PURPOSE: HCC incidence has been continuously rising in the US for the past 30 years. To understand the increase in HCC risk, we conducted a case-control study in Connecticut, New Jersey and part of New York City. METHODS: Through rapid case ascertainment and random digit dialing, we recruited 673 incident HCC patients and 1,166 controls. Information on demographic and anthropometric characteristics, lifestyle factors, medical and family cancer histories, were ascertained through telephone interviews using a structured questionnaire. Saliva specimens were collected for testing hepatitis C virus (HCV) antibodies. Unconditional logistic regression models were utilized to calculate odds ratio (OR) and 95% confidence interval (CI) to determine HCC associations with risk factors. RESULTS: The study confirmed that HCV infection and obesity were important risk factors for HCC, ORs 110 (95% CI 59.2-204) and 2.13 (95% CI 1.52-3.00), respectively. High BMI and HCV infection had synergy in association with elevated HCC risk. Patients both obese and infected with HCV had HCC detected on average nearly 10 years earlier than those with neither factor. Diabetes, cigarette smoking and heavy alcohol intake were all associated with increased risk of HCC, whereas aspirin and other NSAID use were associated with reduced risk. HCC cases tended to attain less education, with lower household incomes, unmarried, and to have had more sexual partners than the controls. CONCLUSIONS: Individuals at risk of HCC in the US comprise a unique population with low socioeconomic status and unhealthy lifestyle choices. Given the multifactorial nature, a comprehensive approach is needed in HCC prevention.

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.