Improving Outcomes After Relapse in Ewing's Sarcoma: Analysis of 114 Patients From a Single Institution

The outcome for patients with relapsed Ewing's sarcoma is poor. A retrospective analysis was carried out to identify factors associated with improved survival. Between 1992 and 2002, 114 patients presented with relapsed or progressive disease. Median time to progression/relapse was 13 months (range, 2–128). Treatment at relapse included high dose treatment (HDT) in 29 patients, and surgery or definitive radiotherapy in 29. 2 and 5-year post relapse survival (PRS) was 23.5% and 15.2%, respectively. In multivariate analysis, the most significant factors associated with improved survival were disease confined locally or to the lungs (2-year PRS, 40% versus 6%; P < .001), relapse > 18 months from diagnosis (2-year PRS, 53% versus 8%; P < .001), HDT at relapse (2-year PRS, 62% versus 11%; P < .001), and surgery and/or radiotherapy at relapse (2-year PRS, 51% versus 14%; P < .001). First treatment failure in Ewing's sarcoma is mostly fatal. Improved survival can be achieved in selective patients with aggressive treatment. These improvements are confined to those without bone or bone marrow metastases

No effect of aspirin on mammographic density in a randomized controlled clinical trial.

BACKGROUND: Epidemiologic studies suggest a reduced risk of breast cancer among women who regularly use aspirin; a plausible mechanism is through aspirin effect on mammographic breast density, a breast cancer risk factor, possibly mediated through aspirin interference with estrogen synthesis. METHODS: In a 2-arm randomized placebo-controlled clinical trial, we evaluated the effects of 6-month administration of 325 mg/day aspirin on total mammographic breast dense area and percent of the mammographic breast image occupied by dense areas (% density) in 143 postmenopausal women. Eligible women, recruited from 2005 to 2007, were healthy, not taking hormone therapy, with elevated mammographic breast density (American College of Radiology Breast Imaging Reporting and Data System density category 2, 3, or 4) within 6 months before enrollment. RESULTS: Women were a mean (SD) 59.5 (5.5) years. Geometric mean baseline percent density was 17.6% (95% confidence interval, 14.8-20.9) in women randomized to aspirin and 19.2% (95% confidence interval, 16.3-22.7) in women randomized to placebo. Percent density decreased in women randomized to aspirin by an absolute 0.8% versus an absolute decrease of 1.2% in controls (P = 0.84). Total breast area and dense area decreased to a similar degree in women assigned to aspirin and in those assigned to placebo, with no statistically significant differences between trial arms. CONCLUSIONS: A single daily administration of adult-dose aspirin for 6 months had no effect on mammographic density in postmenopausal women. If aspirin affects breast cancer risk in postmenopausal women, it may do so through alternative pathways than mammographic breast density. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1524-30)

Use of complementary and alternative medicine and breast cancer survival in the Health, Eating, Activity, and Lifestyle Study

PURPOSE: Use of complementary and alternative medicine (CAM) is common among breast cancer patients, but less is known about whether CAM influences breast cancer survival. METHODS: Health Eating, Activity, and Lifestyle (HEAL) Study participants (n = 707) were diagnosed with stage I-IIIA breast cancer. Participants completed a 30-month post-diagnosis interview including questions on CAM use (natural products such as dietary and botanical supplements, alternative health practices, and alternative medical systems), weight, physical activity, and comorbidities. Outcomes were breast cancer-specific and total mortality, which were ascertained from the Surveillance Epidemiology and End Results registries in Western Washington, Los Angeles County, and New Mexico. Cox proportional hazards regression models were fit to data to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for mortality. Models were adjusted for potential confounding by sociodemographic, health, and cancer-related factors. RESULTS: Among 707 participants, 70 breast cancer-specific deaths and 149 total deaths were reported. 60.2 % of participants reported CAM use post-diagnosis. The most common CAM were natural products (51 %) including plant-based estrogenic supplements (42 %). Manipulative and body-based practices and alternative medical systems were used by 27 and 13 % of participants, respectively. No associations were observed between CAM use and breast cancer-specific (HR 1.04, 95 % CI 0.61-1.76) or total mortality (HR 0.91, 95 % CI 0.63-1.29). CONCLUSION: Complementary and alternative medicine use was not associated with breast cancer-specific mortality or total mortality. Randomized controlled trials may be needed to definitively test whether there is harm or benefit from the types of CAM assessed in HEAL in relation to mortality outcomes in breast cancer survivors

Randomized trial of exercise in sedentary middle aged women: effects on quality of life

Increasing physical activity is currently considered to be a possible prevention strategy for cancer, obesity, and cardiovascular disease, either alone or in combination with dietary changes. This paper presents results of a randomized trial of moderate-to-vigorous intensity exercise in middle aged, sedentary women; specifically, we report changes in and correlates of quality of life and functional status of this exercise intervention program for both the short (three months) and longer term (12 months). The intervention group showed a significant increase in Mental Health score from baseline to 3 months (p < .01), significantly greater than the change in the control group at 3 months (p < .01). A similar trend among exercisers was observed for the General Health score (p < .01), and this finding was significantly greater than the change in control group at 3 months (p = .01). Change in Social Support – Affection were predictors of the changes in quality of life variables. This study documented improvements in quality of life and general functioning that occurred as a result of participating in an exercise intervention in sedentary middle-aged women

Independent and Combined Effects of Dietary Weight Loss and Exercise on Leukocyte Telomere Length in Postmenopausal Women

Objective: Investigate the effects of 12 months of dietary weight loss and/or aerobic exercise on leukocyte telomere length in postmenopausal women. Design and Methods 439 overweight or obese women (50–75 y) were randomized to: i) dietary weight loss (N=118); ii) aerobic exercise (N=117), iii) diet + exercise (N=117), or iv) control (N=87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 mins/day, 5 days/week of moderate-to-vigorous aerobic activity. Fasting blood samples were taken at baseline and 12 months. DNA was extracted from isolated leukocytes and telomere length was measured by quantitative-polymerase chain reaction (qPCR). Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. Results: Baseline telomere length was inversely associated with age (r=−0.12 p<0.01) and positively associated with maximal oxygen uptake (r=0.11, p=0.03), but not with BMI or %body fat. Change in telomere length was inversely correlated with baseline telomere length (r=−0.47, p<0.0001). No significant difference in leukocyte telomere length was detected in any intervention group compared to controls, nor was the magnitude of weight loss associated with telomere length at 12 months. Conclusions: Twelve-months of dietary weight loss and exercise did not change telomere length in postmenopausal women

The Piper Fatigue Scale-12 (PFS-12): psychometric findings and item reduction in a cohort of breast cancer survivors

Brief, valid measures of fatigue, a prevalent and distressing cancer symptom, are needed for use in research. This study’s primary aim was to create a shortened version of the revised Piper Fatigue Scale (PFS-R) based on data from a diverse cohort of breast cancer survivors. A secondary aim was to determine whether the PFS captured multiple distinct aspects of fatigue (a multidimensional model) or a single overall fatigue factor (a unidimensional model)

No reduction in C-reactive protein following a 12-month randomized controlled trial of exercise in men and women.

Low-grade systemic inflammation is suggested to play a role in the development of several chronic diseases including cancer. Higher levels of physical activity and lower adiposity have been associated with reduced levels of markers of systemic inflammation, such as C-reactive protein (CRP); however, reductions in CRP have not been observed consistently in randomized controlled trials of exercise. Purpose: To examine the effect of a 12-month aerobic exercise intervention on CRP levels in men and women. Methods: 102 men and 100 women, sedentary and aged 40-75 years, mean BMI of 29.9 and 28.7 kg/m2, respectively, were randomly assigned to a 12-month moderate-to-vigorous aerobic exercise intervention (6 d/wk, 60 min/d, 60-85% maximum heart rate) or control group. Fasting blood samples were collected at baseline and at 12-months. CRP levels were measured by high-sensitivity latex-enhanced nephelometry. Results: At baseline, CRP was 1.16 mg/L and 2.11 for men and women, respectively, and CRP was correlated with percent body fat (r=0.48, p ≤0.001), BMI (r=0.37, p ≤0.001) and aerobic fitness (r=-0.49, p ≤0.001). No intervention effects were observed for CRP in men or women, or when stratified by baseline BMI (< 30 kg/m2 vs. ≥ 30 kg/m2) , baseline CRP (< 3 mg/L vs. ≥ 3 mg/L) or change in body weight, body composition or aerobic fitness. Conclusion: A 12 month moderate-to-vigorous aerobic exercise intervention did not affect CRP levels in previously sedentary men or women with average-risk CRP values at baseline

Deriving clinically meaningful cut-scores for fatigue in a cohort of breast cancer survivors: a Health, Eating, Activity, and Lifestyle (HEAL) Study

PURPOSE: To empirically determine clinically meaningful cut-scores on the 0-10 response scale of the revised Piper Fatigue Scale (PFS-R) and its shorter version (PFS-12). Breast cancer survivors were classified (i.e., none, mild, moderate, or severe fatigue) based on the cut-scores, and relationships between these cut-scores and decrements in health-related quality of life (HRQOL) were examined. METHODS: A total of 857 breast cancer survivors, stages in situ-IIIa, from the Health, Eating, Activity, and Lifestyle (HEAL) Study were eligible. Survivors completed the PFS-R, SF-36, and a sexual health scale approximately 3 years after diagnosis. Multivariate analysis of covariance was used to examine five fatigue severity cut-score models, controlling for demographics, clinical characteristics, comorbidity, and antidepressant use. Multivariate regression was used to examine HRQOL decrements by cut-score category. RESULTS: Analyses supported two similar fatigue severity cut-score models for the PFS-R and PFS-12: Model A.) none (0), mild (1-3), moderate (4-6), and severe (7-10); and Model D.) none (0), mild (1-2), moderate (3-5), and severe (6-10). For every threshold increase in fatigue severity, clinically meaningful decrements in physical, mental, and sexual health scores were observed, supporting construct validity of the fatigue cut-scores. CONCLUSION: Standardized fatigue cut-scores may enhance interpretability and comparability across studies and populations and guide treating planning

Changes in insulin resistance indicators, IGFs, and adipokines in a year-long trial of aerobic exercise in postmenopausal women

Physical activity is a known modifiable lifestyle means for reducing postmenopausal breast cancer risk, but the biologic mechanisms are not well understood. Metabolic factors may be involved. In this study, we aimed to determine the effects of exercise on insulin resistance (IR) indicators, IGF1, and adipokines in postmenopausal women. The Alberta Physical Activity and Breast Cancer Prevention Trial was a two-armed randomized controlled trial in postmenopausal, inactive, cancer-free women. A year-long aerobic exercise intervention of 225 min/week (n=160) was compared with a control group asked to maintain usual activity levels (n=160). Baseline, 6- and 12-month serum levels of insulin, glucose, IGF1, IGF-binding protein 3 (IGFBP3), adiponectin, and leptin were assayed, and after data collection, homeostasis model assessment of IR (HOMA-IR) scores were calculated. Intention-to-treat analyses were performed using linear mixed models. The treatment effect ratio (TER) of exercisers to controls was calculated. Data were available on 308 (96.3%) women at 6 months and 310 (96.9%) women at 12 months. Across the study period, statistically significant reductions in insulin (TER=0.87, 95% confidence interval (95% CI)=0.81–0.93), HOMA-IR (TER=0.86, 95% CI=0.80–0.93), and leptin (TER=0.82, 95% CI=0.78–0.87), and an increase in the adiponectin/leptin ratio (TER=1.21, 95% CI=1.13–1.28) were observed in the exercise group compared with the control group. No significant differences were observed for glucose, IGF1, IGFBP3, adiponectin or the IGF1/IGFBP3 ratio. Previously inactive postmenopausal women who engaged in a moderate-to-vigorous intensity exercise program experienced changes in insulin, HOMA-IR, leptin, and adiponectin/leptin that might decrease the risk for postmenopausal breast cancer