Maura Harrigan

Randomized Exercise Trial of Aromatase Inhibitor-Induced Arthralgia in Breast Cancer Survivors

PURPOSE Arthralgia occurs in up to 50% of breast cancer survivors treated with aromatase inhibitors (AIs) and is the most common reason for poor AI adherence. We conducted, in 121 breast cancer survivors receiving an AI and reporting arthralgia, a yearlong randomized trial of the impact of exercise versus usual care on arthralgia severity. PATIENTS AND METHODS Eligibility criteria included receiving an AI for at least 6 months, reporting ≥ 3 of 10 for worst joint pain on the Brief Pain Inventory (BPI), and reporting < 90 minutes per week of aerobic exercise and no strength training. Participants were randomly assigned to exercise (150 minutes per week of aerobic exercise and supervised strength training twice per week) or usual care. The BPI, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, and Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire were completed at baseline and at 3, 6, 9, and 12 months. Intervention effects were evaluated using mixed-model repeated measures analysis, with change at 12 months as the primary end point. RESULTS Over 12 months, women randomly assigned to exercise (n = 61) attended 70% (± standard deviation [SD], 28%) of resistance training sessions and increased their exercise by 159 (± SD, 136) minutes per week. Worst joint pain scores decreased by 1.6 points (29%) at 12 months among women randomly assigned to exercise versus a 0.2-point increase (3%) among those receiving usual care (n = 60; P < .001). Pain severity and interference, as well as DASH and WOMAC pain scores, also decreased significantly at 12 months in women randomly assigned to exercise, compared with increases for those receiving usual care (all P < .001). CONCLUSION Exercise led to improvement in AI-induced arthralgia in previously inactive breast cancer survivors.

Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic Review and Meta-Analysis

BACKGROUND Overweight and obesity are associated with breast cancer mortality. However, the relationship between postdiagnosis weight gain and mortality is unclear. We conducted a systematic review and meta-analysis of weight gain after breast cancer diagnosis and breast cancer-specific, all-cause mortality and recurrence outcomes. METHODS Electronic databases identified articles up through December 2014, including: PubMed (1966-present), EMBASE (1974-present), CINAHL (1982-present), and Web of Science. Language and publication status were unrestricted. Cohort studies and clinical trials measuring weight change after diagnosis and all-cause/breast cancer-specific mortality or recurrence were considered. Participants were women age 18 years or older with stage I-IIIC breast cancer. Fixed effects analysis summarized the association between weight gain (≥5.0% body weight) and all-cause mortality; all tests were two-sided. RESULTS Twelve studies (n = 23 832) were included. Weight gain (≥5.0%) compared with maintenance (<±5.0%) was associated with increased all-cause mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.03 to 1.22, P = .01, I(2) = 55.0%). Higher risk of mortality was apparent for weight gain ≥10.0% (HR = 1.23, 95% CI = 1.09 to 1.39, P < .001); 5% to 10.0% weight gain was not associated with all-cause mortality (P = .40). The association was not statistically significant for those with a prediagnosis body mass index (BMI) of less than 25 kg/m(2) (HR = 1.14, 95% CI = 0.99 to 1.31, P = .07) or with a BMI of 25 kg/m(2) or higher (HR = 1.00, 95% CI = 0.86 to 1.16, P = .19). Weight gain of 10.0% or more was not associated with hazard of breast cancer-specific mortality (HR = 1.17, 95% CI = 1.00 to 1.38, P = .05). CONCLUSIONS Weight gain after diagnosis of breast cancer is associated with higher all-cause mortality rates compared with maintaining body weight. Adverse effects are greater for weight gains of 10.0% or higher.

Randomized Trial Comparing Telephone Versus In-Person Weight Loss Counseling on Body Composition and Circulating Biomarkers in Women Treated for Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study

PURPOSE Obesity is associated with a higher risk of breast cancer mortality. The gold standard approach to weight loss is in-person counseling, but telephone counseling may be more feasible. We examined the effect of in-person versus telephone weight loss counseling versus usual care on 6-month changes in body composition, physical activity, diet, and serum biomarkers. METHODS One hundred breast cancer survivors with a body mass index ≥ 25 kg/m(2) were randomly assigned to in-person counseling (n = 33), telephone counseling (n = 34), or usual care (UC) (n = 33). In-person and telephone counseling included 11 30-minute counseling sessions over 6 months. These focused on reducing caloric intake, increasing physical activity, and behavioral therapy. Body composition, physical activity, diet, and serum biomarkers were measured at baseline and 6 months. RESULTS The mean age of participants was 59 ± 7.5 years old, with a mean BMI of 33.1 ± 6.6 kg/m(2), and the mean time from diagnosis was 2.9 ± 2.1 years. Fifty-one percent of the participants had stage I breast cancer. Average 6-month weight loss was 6.4%, 5.4%, and 2.0% for in-person, telephone, and UC groups, respectively (P = .004, P = .009, and P = .46 comparing in-person with UC, telephone with UC, and in-person with telephone, respectively). A significant 30% decrease in C-reactive protein levels was observed among women randomly assigned to the combined weight loss intervention groups compared with a 1% decrease among women randomly assigned to UC (P = .05). CONCLUSION Both in-person and telephone counseling were effective weight loss strategies, with favorable effects on C-reactive protein levels. Our findings may help guide the incorporation of weight loss counseling into breast cancer treatment and care.

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

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 Mens Christian Associations (YMCAs) across the United States, on PA, fitness, quality of life, fatigue, body composition, serum biomarkers, and program safety in cancer survivors.

Abstract S3-03: Randomized trial of exercise vs. usual care on aromatase inhibitor-associated arthralgias in women with breast cancer: The hormones and physical exercise (HOPE) study

PURPOSE: Arthralgias occur in up to 50% of women with breast cancer treated with adjuvant aromatase inhibitors (AIs), and are one of the most common reasons for poor adherence to therapy. We examined whether a year-long exercise program improves arthralgias in breast cancer survivors taking AIs. METHODS: Postmenopausal women diagnosed with hormone receptor-positive breast cancer were identified via the Connecticut Tumor Registry. Women who were taking an AI for at least 6-months and reported ≥ 3 out of 10 on the worst joint pain item of the Brief Pain Inventory-Short Form (BPI) were eligible and randomized to either exercise (150 min/wk of moderate-intensity aerobic exercise and twice-weekly supervised resistance exercise sessions) or usual care. The BPI questionnaire was completed at baseline, 6- and 12-months. VO2 max testing and Dual Energy X-ray Absorptiometry (DEXA) scans were also collected at baseline, 6- and 12-months. The primary outcome was change in BPI worst joint pain score between 0 and 12 months. We performed intent-to-treat statistical analyses including analysis of covariance, where each participant9s change in outcome was modeled as a function of randomization group RESULTS: Out of 728 women screened that were taking an AI, we randomized 121 women, with 61 women randomized to exercise and 60 women randomized to usual care. Baseline characteristics were comparable between the two groups. Over 12 months, women randomized to exercise attended, on average, 80% ± 14% of the twice-weekly supervised resistance training exercise sessions and participated in an average 146 ± 75 min/wk of at least moderate-intensity aerobic exercise. Worst joint pain scores decreased by 20% at 12 months among women randomized to exercise vs. a 3% decrease among women randomized to usual care (p = .017). Joint pain severity also decreased significantly in exercise vs. usual care groups (p = 0.025), as well as joint pain-related interference (p = 0.005). The exercise intervention also favorably impacted body weight (p = 0.0057) and cardiorespiratory fitness (p = 0.024). CONCLUSION: We found that participating in an exercise intervention led to clinically meaningful improvements in AI-induced arthralgias in breast cancer survivors experiencing moderate joint pain. The intervention also induced favorable changes in body weight and cardiorespiratory fitness, factors that may be linked to incidence and severity of AI-induced arthralgias. Further work is needed to determine whether exercise leads to increased AI adherence and possibly better outcomes in women with breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S3-03.

The effect of exercise on body composition and bone mineral density in breast cancer survivors taking aromatase inhibitors

This study examined the effect of 12 months of aerobic and resistance exercise versus usual care on changes in body composition in postmenopausal breast cancer survivors taking aromatase inhibitors (AIs).

Changes in diet quality in a randomized weight loss trial in breast cancer survivors: the lifestyle, exercise, and nutrition (LEAN) study

Obesity is associated with increased breast cancer recurrence and mortality. Though some post-diagnosis weight loss interventions have achieved weight loss outcomes, it is unclear whether they also improve diet quality. In the Lifestyle, Exercise, and Nutrition (LEAN) study, overweight or obese breast cancer survivors were randomized to either usual care group (n=33) or the 6-month lifestyle intervention (n=67). Dietary intake was assessed at baseline and 6 months using a validated food frequency questionnaire, and overall diet quality was calculated using the Healthy Eating Index (HEI)-2010 (range 0–100). Intervention effects on diet were evaluated with generalized linear models. Among the 81 participants (51 intervention, 30 usual care) with dietary data, the mean baseline HEI score was 70.5 (s.d.=8.8) and was improved at 6 months (intervention group=6.8 point increase vs usual care=3.1, P=0.09). Intervention group participants achieved greater reductions in percent of energy from total fat (−4.2% vs −1.2%; P=0.013) and saturated fat (−2.2% vs −1.1%; P=0.003), and greater increases in fiber (4.8 g per 1000 kcal vs 1.3 g per 1000 kcal; P=0.007) and fruit (0.5 servings vs 0.0 servings; P=0.006) intake. Intervention group participants who lost ⩾5% body weight (n=27) demonstrated significantly greater improvements in HEI score (10.4 vs 2.8) than those who lost <5% (n=23). The intervention increased fruit and fiber intake and decreased percent energy from fat, and those with greater weight loss achieved greater increases in overall diet quality. These findings support the ability of a weight loss intervention to improve diet among breast cancer survivors.

Randomized Trial of Exercise on Quality of Life in Women With Ovarian Cancer: Women’s Activity and Lifestyle Study in Connecticut (WALC)

Background Ovarian cancer survivors experience a wide range of treatment side effects that can negatively affect health-related quality of life (HRQOL). Physical activity has been shown to improve HRQOL and cancer-related fatigue (CRF) for other cancer survivors; however, no large randomized controlled trial (RCT) has been conducted for ovarian cancer. Methods This study examined the impact of a six-month RCT of exercise vs attention control on change in HRQOL (Short Form Health Survey-36) and CRF (Functional Assessment of Cancer Therapy-Fatigue Scale) in ovarian cancer survivors. Women (n = 144) were randomly assigned to study arms between May 1, 2010, and March 20, 2014. All statistical tests were two-sided. Results A total of 74 women were randomly assigned to exercise and 70 to attention control. A total of 113 (78.5%) of the participants completed the six-month assessment. Adherence to the exercise intervention was excellent (166.0±66.1 minutes/week in the exercise arm). At six months, women in the exercise arm had improved physical HRQOL (SF-36 Physical Component Summary Score) compared with the control arm, 1.8 (SD = 1.1) vs -2.0 (SD = 1.2) , respectively (group difference = 3.7, SD = 1.2, 95% confidence interval [CI] = 0.7 to 6.8, P = .02). No group differences were seen for change in mental HRQOL. There was a statistically significant improvement in the fatigue score (Functional Assessment of Cancer Therapy-Fatigue) for exercisers (4.0, SD = 1.1, 95% CI = 1.8 to 6.2, P < .001) but not for controls (1.2, SD = 1.2, 95% CI = -1.1 to 3.5, P = .31), with a between-group difference of 2.8 (SD = 1.5, 95% CI = -0.2 to 5.7, P = .06). Conclusions We found a six-month home-based, telephone-delivered exercise intervention of primarily brisk walking to be associated with improved physical HRQOL in women with ovarian cancer. Given that higher HRQOL and exercise have both been associated with overall survival in women diagnosed with ovarian cancer, oncologists and primary care providers should recommend and refer women diagnosed with ovarian cancer to clinic- or community-based exercise programs.

Lymphedema in ovarian cancer survivors: Assessing diagnostic methods and the effects of physical activity: Lymphedema in Ovarian Cancer Survivors

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.

Abstract 5321: Metabolomics and body mass index among breast cancer survivors in The Lifestyle, Exercise, and Nutrition (LEAN) Study

Background: While there is a growing body of literature on metabolomics and body mass index (BMI), there are limited studies in relation to weight change in overweight and obese individuals, and to our knowledge, no such studies in breast cancer survivors. Methods: The Lifestyle, Exercise and Nutrition (LEAN) randomized diet- and exercise-induced weight loss trial in breast cancer survivors enrolled overweight or obese breast cancer survivors (Stage 0-III) identified via the Yale-New Haven Hospital tumor registry or self-referral. Participants were randomized to either usual care group (n=33) or the 6-month lifestyle intervention (11 sessions with a registered dietitian) (n=67). Height and weight were measured by study staff at baseline and 6 months, and a fasting (≥ 12 hours) blood draw was also performed at these time points. Paired (baseline and 6-month) serum metabolomics data were available for 83 women. Only those metabolites consistently detected in >80% of quality control samples with a coefficient of variation Results: Overall, a total of 307 metabolites were analyzed; 168 were quantitated by LC-MS and 139 were semi-quantitated by GC-TOF/MS. For BMI change from baseline to 6-months, we observed correlations with 16 metabolites (isocitric acid, 3-hydroxybutyric acid, serine, L-cysteine, petroselinic acid, aminomalonic acid, palmitoleic acid, linoleic acid, 2-hydroxybutyric acid, and seven unidentified metabolites, p Conclusions: There were no clear associations between metabolites and change in BMI or randomization group among overweight and obese breast cancer survivors enrolled in a weight loss trial. Larger sample sizes would help to clarify if any of the potential signals observed in this population may be associated with BMI or other lifestyle changes, such as diet quality. Citation Format: Leah M. Ferrucci, Brenda Cartmel, Maura Harrigan, Tara Sanft, Mary Playdon, Wei Jia, Herbert Yu, Caroline H. Johnson, Lajos Pusztai, Anees B. Chagpar, Melinda L. Irwin. Metabolomics and body mass index among breast cancer survivors in The Lifestyle, Exercise, and Nutrition (LEAN) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5321. doi:10.1158/1538-7445.AM2017-5321