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.

Association between diet quality and ovarian cancer risk and survival.

BACKGROUND: Research on diet quality and ovarian cancer is limited. We examined the association between diet quality and ovarian cancer risk and survival in a large prospective cohort. METHODS: We utilized data from women in the prospective NIH-AARP Diet and Health Study enrolled from 1995-1996 and were 50-71 years old at baseline with follow-up through 12/31/2017. Participants completed a 124-item Food Frequency Questionnaire at baseline and diet quality was assessed via the Healthy Eating Index-2015 (HEI-2015), the alternate Mediterranean diet score (aMED), and the Dietary Approaches to Stop Hypertension score (DASH). Primary outcomes were first primary epithelial ovarian cancer diagnosis from cancer registry data, and among those diagnosed with ovarian cancer all-cause mortality. We used a semi-Markov multi-state model with Cox proportional hazards regression to account for semi-competing events. RESULTS: Among 150,643 participants with a median follow-up time of 20.5 years, 1,107 individuals were diagnosed with a first primary epithelial ovarian cancer. There was no evidence of an association between diet quality and ovarian cancer risk. Among those diagnosed with epithelial ovarian cancer, 893 deaths occurred with a median survival of 2.5 years. Better pre-diagnosis diet quality, according to the HEI-2015 (Quintile 5 vs Quintile 1 HR = 0.75 [0.60-0.93]) and aMED (Quintile 5 vs Quintile 1: HR = 0.68, [0.53-0.87]) was associated with lower all-cause mortality. There was no evidence of an association between DASH and all-cause mortality. CONCLUSIONS: Better pre-diagnosis diet quality was associated with lower all-cause mortality after ovarian cancer diagnosis, but was not associated with ovarian cancer risk.

Effect of a Personalized Tobacco Treatment Intervention on Smoking Abstinence in Individuals Eligible for Lung Cancer Screening.

INTRODUCTION: To determine whether personalized gain-framed messaging and biomarker feedback related to tobacco cessation or reduction decrease smoking behavior in patients undergoing or eligible for lung cancer screening. METHODS: Between 2016 and 2020, 188 patients were enrolled in a two-phase, sequential, randomized controlled trial. Phase 1 evaluated whether standard of care (SC) (five in-person counseling sessions and 8 weeks of nicotine patch) plus gain-framed messaging (GFM) versus SC would increase 8-week biochemically verified smoking cessation rates. In 143 participants randomized in phase 2, we tested whether feedback on smoking-related biomarkers would reduce 6-month self-reported number of cigarettes smoked per day compared with a no feedback control. Chi-square test and mixed effects repeated measures analyses were used to evaluate group differences. RESULTS: Participants were 62.5 ± 5.6 (mean ± SD) years of age, had a 50.3 ± 21 pack-year smoking history, and were smoking 16.9 ± 9.9 cigarettes per day. At 8 weeks, there was no difference in quit rates between those randomized to SC plus GFM (n = 15 of 93, 16.1%) and those randomized to SC (n = 16 of 95, 16.8%), with p equals to 0.90. At the 6-month post-randomization follow-up, number of cigarettes smoked per day was similar in the feedback (least-squares mean = 7.5, 95% confidence interval: 6.0-9.1) and no feedback arms (7.7, 95% confidence interval: 6.2-9.3), with p equals to 0.87. CONCLUSIONS: Gain-framed messaging and health feedback did not significantly improve quit rates relative to comprehensive standard of care. Nevertheless, the overall program achieved clinically meaningful smoking quit rates in this older high pack-year cohort, highlighting the importance of intensive tobacco treatment for patients undergoing lung cancer screening. CLINICAL TRIAL REGISTERED WITH CLINICALTRIALS.GOV: NCT02658032.

Post-diagnosis weight trajectories and mortality among women with breast cancer.

Weight gain after breast cancer diagnosis is associated with adverse health outcomes. Yet, few studies have characterized post-diagnosis weight change in the modern treatment era or populations most at risk for weight changes. Among women diagnosed with stages I-III breast cancer in the Smilow Care Network (2013-2019; N = 5441), we abstracted demographic and clinical characteristics from electronic health records and survival data from tumor registries. We assessed if baseline characteristics modified weight trajectories with nonlinear multilevel mixed-effect models. We evaluated body mass index (BMI) at diagnosis and weight change 1-year post-diagnosis in relation to all-cause and breast cancer-specific mortality with Cox proportional hazard models. Women had 34.4 ± 25.5 weight measurements over 3.2 ± 1.8 years of follow-up. Weight gain was associated with ER/PR-, HER2+ tumors, BMI ≤ 18.5 kg/m2, and age ≤ 45 years (+4.90 kg (standard error [SE] = 0.59), +3.24 kg (SE = 0.34), and +1.75 kg (SE = 0.10), respectively). Weight loss was associated with BMI ≥ 35 kg/m2 and age ≥ 70 years (-4.50 kg (SE = 0.08) and -4.34 kg (SE = 0.08), respectively). Large weight loss (≥10%), moderate weight loss (5-10%), and moderate weight gain (5-10%) 1-year after diagnosis were associated with higher all-cause mortality (hazard ratio [HR] = 2.93, 95% confidence interval [CI] = 2.28-3.75, HR = 1.32, 95% CI = 1.02-1.70 and HR = 1.39, 95% CI = 1.04-1.85, respectively). BMI ≥ 35 kg/m2 or BMI ≤ 18.5 kg/m2 at diagnosis were also associated with higher all-cause mortality. Weight change after a breast cancer diagnosis differed by demographic and clinical characteristics highlighting subgroups at-risk for weight change during a 5-year period post-diagnosis. Monitoring and interventions for weight management early in clinical care are important.

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.

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.

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.

A review of the impact of energy balance on triple-negative breast cancer.

Cancer cells cannot proliferate without sufficient energy to generate biomass for rapid cell division, as well as to fuel their functions at baseline. For this reason, many recent observational and interventional studies have focused on increasing energy expenditure and/or reducing energy intake during and after cancer treatment. The impact of variance in diet composition and in exercise on cancer outcomes has been detailed extensively elsewhere and is not the primary focus of this review. Instead, in this translational, narrative review we examine studies of how energy balance impacts anticancer immune activation and outcomes in triple-negative breast cancer (TNBC). We discuss preclinical, clinical observational, and the few clinical interventional studies on energy balance in TNBC. We advocate for the implementation of clinical studies to examine how optimizing energy balance-through changes in diet and/or exercise-may optimize the response to immunotherapy in people with TNBC. It is our conviction that by taking a holistic approach that includes energy balance as a key factor to be considered during and after treatment, cancer care may be optimized, and the detrimental effects of cancer treatment and recovery on overall health may be minimized.

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.

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.

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.

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.

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.

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.

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.

Mode of Delivery, Birth Characteristics, and Early-Onset Non-Hodgkin Lymphoma in a Population-Based Case-Control Study.

BACKGROUND: The etiology of non-Hodgkin lymphoma (NHL) in children and in adolescents and young adults (AYA) is not well understood. METHODS: We evaluated potential associations between mode of delivery, birth characteristics, and NHL risk in a population-based case-control study, which included 3,064 cases of NHL [490 with Burkitt lymphoma, 981 with diffuse large B-cell lymphoma (DLBCL), and 978 with T-cell NHL) diagnosed at the age of 0 to 37 years in California during 1988 to 2015 and 153,200 controls frequency matched on year of birth. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from an unconditional multivariable logistic regression model that included year of birth and birth characteristics. RESULTS: Individuals born via cesarean section had a decreased risk of pediatric Burkitt lymphoma (age 0-14 years; OR = 0.71, 95% CI: 0.51-0.99) and pediatric T-cell NHL (OR = 0.73, 95% CI: 0.55-0.97) compared with those born vaginally. Having a birth order of second (OR = 0.73, 95% CI: 0.57-0.93) or third or higher (OR = 0.76, 95% CI: 0.58-0.99) was associated with a lower risk of pediatric T-cell NHL compared with first-borns. AYA (age 15-37 years) with a heavier birthweight had an elevated risk of DLBCL (OR for each kg = 1.16, 95% CI: 1.00-1.35). Associations between other birth characteristics, including plurality, maternal age, maternal education, and NHL risk, also exhibited variations across subgroups based on age of diagnosis and histologic subtype. CONCLUSIONS: These findings support a role of mode of delivery and birth characteristics in the etiology of early-onset NHL. IMPACT: This study underscores the etiologic heterogeneity of early-onset NHL.

Effect of healthy diet and exercise on chemotherapy completion rate in women with breast cancer: The Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) study: Study protocol for a randomized clinical trial.

BACKGROUND: The World Cancer Research Fund and the American Cancer Society provide nutrition and physical activity guidelines for cancer survivors. Many women with breast cancer do not follow these guidelines and delay efforts toward following them until active treatment is complete. However, adoption of these recommended lifestyle behaviors soon after diagnosis may prevent adverse treatment-related side effects and may improve adherence to treatment, resulting in improved breast cancer prognosis. The Lifestyle, Exercise, and Nutrition Early after Diagnosis (LEANer) study is testing the effect of a nutrition and physical activity intervention on chemotherapy completion rates. METHODS: 172 women with stage I-III breast cancer undergoing chemotherapy will be randomized 1:1 to a yearlong, 16 session, nutrition and exercise intervention or usual care control group. The intervention is delivered by registered dietitians specializing in oncology nutrition and exercise training. The intervention includes goal setting to meet nutrition and physical activity guidelines for cancer survivors. After each chemotherapy session, date and dose of each drug administered, and reason for dose-adjustments and/or dose-delays are abstracted from the electronic medical record or obtained from the treating oncologist. Chemotherapy completion rate is assessed as the average relative dose-intensity (RDI) for the originally planned regimen based on standard formulas. Secondary endpoints of endocrine therapy adherence, treatment-related side effects, and changes in inflammatory and metabolic biomarkers, body composition, and patient reported outcomes are assessed at four timepoints. DISCUSSION: If successful, this study has the potential to make healthy lifestyle interventions a standard component of breast cancer treatment.

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.

Cognitive Effects and Depression Associated With Taxane-Based Chemotherapy in Breast Cancer Survivors: A Meta-Analysis.

Purpose: This meta-analysis provides a longitudinal assessment of depression and cognitive impairment induced by taxane-based chemotherapy in women with breast cancer after 6 months of treatment. We highlighted the incidence and prevalence, the cognitive pattern in neuropsychological studies, and the relationship between chemotherapy-induced cognitive impairment and different risk factors. We estimated the effect sizes on each cognitive domain and differentiated effect sizes by each method of comparison of effects (i.e., baseline data, or control groups). Methods: The databases MEDLINE and Embase were searched for publications about taxane-related cognitive changes in patients with breast cancer published from 1980 to 2019. Cross-sectional and self-reported outcomes studies were excluded except for the depression item. Included studies were assessed for risk of bias with the Newcastle-Ottawa Scale. We estimated effect sizes for each cognitive domain and differentiated effect sizes by each method of comparison of effects. The review is reported in compliance with the PRISMA Statement; it was registered prospectively in PROSPERO as CRD42020163255. Results: Eleven studies meeting the criteria were analyzed, which resulted in a sample of 1,057 patients with breast cancer who received chemotherapy including 820 patients (77%) who received taxane-based chemotherapy. Attention and concentration, depression, and executive function domains had significant chemotherapy-induced impairment across all comparison types. Statistically significant improvement was found in language and verbal memory when comparing chemotherapy patients' test scores with baseline or matched controls. Taxane-based chemotherapy had a non-significant effect on processing speed, visual memory, visuospatial, and motor function domains. Conclusions: The occurrence of chemotherapy-induced cognitive impairment 6 months or more after the course of treatment in people with breast cancer is frequent in the domains of attention, executive function, and depression. Other domains appear stable or improve with time after treatment cessation.