Jennifer A. Ligibel

Impact of a Mixed Strength and Endurance Exercise Intervention on Insulin Levels in Breast Cancer Survivors

PURPOSE Accumulating data suggest that exercise may affect breast cancer risk and outcomes. Studies have demonstrated that high levels of insulin, often seen in sedentary individuals, are associated with increased risk of breast cancer recurrence and death. We sought to analyze whether exercise lowered insulin concentrations in breast cancer survivors. METHODS One hundred one sedentary, overweight breast cancer survivors were randomly assigned either to a 16-week cardiovascular and strength training exercise intervention or to a usual care control group. Fasting insulin and glucose levels, weight, body composition, and circumference at the waist and hip were collected at baseline and 16 weeks. RESULTS Baseline and 16-week measurements were available for 82 patients. Fasting insulin concentrations decreased by an average of 2.86 microU/mL in the exercise group (P = .03), with no significant change in the control group (decrease of 0.27 microU/mL, P = .65). The change in insulin levels in the exercise group seemed greater than the change in controls, but the comparison did not reach statistical significance (P = .07). There was a trend toward improvement in insulin resistance in the exercise group (P = .09) but no change in fasting glucose levels. The exercise group also experienced a significant decrease in hip measurements, with no change in weight or body composition. CONCLUSION Participation in an exercise intervention was associated with a significant decrease in insulin levels and hip circumference in breast cancer survivors. The relationship between physical activity and breast cancer prognosis may be mediated, in part, through changes in insulin levels and/or changes in body fat or fat deposition.

American Society of Clinical Oncology Position Statement on Obesity and Cancer

Rates of obesity have increased significantly over the last three decades in the United States and globally. In addition to contributing to heart disease and diabetes, obesity is a major unrecognized risk factor for cancer. Obesity is associated with worsened prognosis after cancer diagnosis and also negatively affects the delivery of systemic therapy, contributes to morbidity of cancer treatment, and may raise the risk of second malignancies and comorbidities. Research shows that the time after a cancer diagnosis can serve as a teachable moment to motivate individuals to adopt risk-reducing behaviors. For this reason, the oncology care team--the providers with whom a patient has the closest relationships in the critical period after a cancer diagnosis--is in a unique position to help patients lose weight and make other healthy lifestyle changes. The American Society of Clinical Oncology is committed to reducing the impact of obesity on cancer and has established a multipronged initiative to accomplish this goal by 1) increasing education and awareness of the evidence linking obesity and cancer; 2) providing tools and resources to help oncology providers address obesity with their patients; 3) building and fostering a robust research agenda to better understand the pathophysiology of energy balance alterations, evaluate the impact of behavior change on cancer outcomes, and determine the best methods to help cancer survivors make effective and useful changes in lifestyle behaviors; and 4) advocating for policy and systems change to address societal factors contributing to obesity and improve access to weight management services for patients with cancer.

Screening, Assessment, and Management of Fatigue in Adult Survivors of Cancer: An American Society of Clinical Oncology Clinical Practice Guideline Adaptation

PURPOSE This guideline presents screening, assessment, and treatment approaches for the management of adult cancer survivors who are experiencing symptoms of fatigue after completion of primary treatment. METHODS A systematic search of clinical practice guideline databases, guideline developer Web sites, and published health literature identified the pan-Canadian guideline on screening, assessment, and care of cancer-related fatigue in adults with cancer, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines In Oncology (NCCN Guidelines) for Cancer-Related Fatigue and the NCCN Guidelines for Survivorship. These three guidelines were appraised and selected for adaptation. RESULTS It is recommended that all patients with cancer be evaluated for the presence of fatigue after completion of primary treatment and be offered specific information and strategies for fatigue management. For those who report moderate to severe fatigue, comprehensive assessment should be conducted, and medical and treatable contributing factors should be addressed. In terms of treatment strategies, evidence indicates that physical activity interventions, psychosocial interventions, and mind-body interventions may reduce cancer-related fatigue in post-treatment patients. There is limited evidence for use of psychostimulants in the management of fatigue in patients who are disease free after active treatment. CONCLUSION Fatigue is prevalent in cancer survivors and often causes significant disruption in functioning and quality of life. Regular screening, assessment, and education and appropriate treatment of fatigue are important in managing this distressing symptom. Given the multiple factors contributing to post-treatment fatigue, interventions should be tailored to each patients specific needs. In particular, a number of nonpharmacologic treatment approaches have demonstrated efficacy in cancer survivors.

Metformin in Breast Cancer: Time for Action

Pamela J. Goodwin, Samuel Lunenfeld Research Institute, Mount Sinai Hospital; and Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada Jennifer A. Ligibel, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard School of Medicine, Boston, MA Vuk Stambolic, Division of Signaling Biology, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada

The Role of Obesity in Cancer Survival and Recurrence

Obesity and components of energy imbalance, that is, excessive energy intake and suboptimal levels of physical activity, are established risk factors for cancer incidence. Accumulating evidence suggests that these factors also may be important after the diagnosis of cancer and influence the course of disease, as well as overall health, well-being, and survival. Lifestyle and medical interventions that effectively modify these factors could potentially be harnessed as a means of cancer control. However, for such interventions to be maximally effective and sustainable, broad sweeping scientific discoveries ranging from molecular and cellular advances, to developments in delivering interventions on both individual and societal levels are needed. This review summarizes key discussion topics that were addressed in a recent Institute of Medicine Workshop entitled, “The Role of Obesity in Cancer Survival and Recurrence”; discussions included (i) mechanisms associated with obesity and energy balance that influence cancer progression; (ii) complexities of studying and interpreting energy balance in relation to cancer recurrence and survival; (iii) associations between obesity and cancer risk, recurrence, and mortality; (iv) interventions that promote weight loss, increased physical activity, and negative energy balance as a means of cancer control; and (v) future directions. Cancer Epidemiol Biomarkers Prev; 21(8); 1244–59. ©2012 AACR.

Evaluation of metformin in early breast cancer: a modification of the traditional paradigm for clinical testing of anti-cancer agents

Metformin, an inexpensive oral agent commonly used to treat type 2 diabetes, has been garnering increasing attention as a potential anti-cancer agent. Preclinical, epidemiologic, and clinical evidences suggest that metformin may reduce overall cancer risk and mortality, with specific effects in breast cancer. The extensive clinical experience with metformin, coupled with its known (and modest) toxicity, has allowed the traditional process of drug evaluation to be shortened. We review the rationale for a modified approach to evaluation and outline the key steps that will optimize development of this agent in breast cancer, including discussion of a Phase III adjuvant trial (NCIC MA.32) that has recently been initiated.

Central Venous Catheter Care for the Patient With Cancer: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To develop an evidence-based guideline on central venous catheter (CVC) care for patients with cancer that addresses catheter type, insertion site, and placement as well as prophylaxis and management of both catheter-related infection and thrombosis. METHODS A systematic search of MEDLINE and the Cochrane Library (1980 to July 2012) identified relevant articles published in English. RESULTS The overall quality of the randomized controlled trial evidence was rated as good. There is consistency among meta-analyses and guidelines compiled by other groups as well. RECOMMENDATIONS There is insufficient evidence to recommend one CVC type or insertion site; femoral catheterization should be avoided. CVC should be placed by well-trained providers, and the use of a CVC clinical care bundle is recommended. The use of antimicrobial/antiseptic-impregnated and/or heparin-impregnated CVCs is recommended to decrease the risk of catheter-related infections for short-term CVCs, particularly in high-risk groups; more research is needed. The prophylactic use of systemic antibiotics is not recommended before insertion. Data are not sufficient to recommend for or against routine use of antibiotic flush/lock therapy; more research is needed. Before starting antibiotic therapy, cultures should be obtained. Some life-threatening infections require immediate catheter removal, but most can be treated with antimicrobial therapy while the CVC remains in place. Routine flushing with saline is recommended. Prophylactic use of warfarin or low-molecular weight heparin is not recommended, although a tissue plasminogen activator (t-PA) is recommended to restore patency to occluded catheters. CVC removal is recommended when the catheter is no longer needed or if there is a radiologically confirmed thrombosis that worsens despite anticoagulation therapy.

Risk Perceptions and Psychosocial Outcomes of Women With Ductal Carcinoma In Situ: Longitudinal Results From a Cohort Study

BACKGROUND Ductal carcinoma in situ (DCIS) has a generally favorable overall prognosis, with a systemic recurrence rate of approximately 1%, a local recurrence rate after mastectomy of 1%, and a local recurrence rate after breast-conserving treatment of less than 10%. Preliminary studies have suggested that women with DCIS may overestimate their risk of disease recurrence. Few data exist regarding psychosocial outcomes for women with DCIS. METHODS Women in Eastern Massachusetts with newly diagnosed DCIS were asked to participate in a longitudinal study of risk perceptions, psychosocial concerns, and health behaviors. Psychosocial outcomes after DCIS diagnosis and risk perceptions were evaluated at enrollment and at 9 and 18 months. All statistical tests were two-sided. RESULTS Four hundred eighty-seven women with DCIS (64% of eligible participants) completed the enrollment survey. Overall quality of life was good among the women surveyed, and the substantial anxiety at enrollment decreased with time (P < .001). At enrollment, 54% perceived at least a moderate risk for DCIS recurrence in the next 5 years, 68% in their lifetime; 39% perceived at least a moderate risk for invasive cancer in the next 5 years, 53% in their lifetime; and 28% perceived at least a moderate likelihood of DCIS spreading to other places in their body. At 18 months after enrollment, perceived risks had not statistically significantly changed from those at enrollment (P = .38). Anxiety at enrollment was the factor that was most consistently and strongly associated with overestimation of future breast cancer-related risks (perceived moderate or greater risk vs less than moderate risk of DCIS recurring within 5 years: odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.6 to 9.9, P = .003; of invasive breast cancer within 5 years: OR = 4.3, 95% CI = 1.9 to 9.9, P < .001; and of invasive breast cancer during lifetime: OR = 5.3, 95% CI = 2.0 to 14.3, P < .001). CONCLUSIONS Many women with newly diagnosed DCIS have inaccurate perceptions of the breast cancer risks that they face, and anxiety is particularly associated with these inaccurate perceptions.

Obesity at Diagnosis Is Associated With Inferior Outcomes in Hormone Receptor-Positive Operable Breast Cancer

Obesity has been associated with inferior outcomes in operable breast cancer, but the relation between body mass index (BMI) and outcomes by breast cancer subtype has not been previously evaluated.

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.