Exercise to Prevent Aromatase Inhibitor Side Effects in Breast Cancer Patients
Keywords
Abstract
Description
Breast cancer is the most common malignancy in women in the United States and is the second leading cause of cancer deaths. In 2013, an estimated 230,000 women in the United States will be diagnosed with invasive breast cancer and approximately 40,000 with die.1 Women with breast cancer frequently experience significant functional and metabolic declines during and after treatment due to cancer-related fatigue (CRF), stress and depression.2,3 Cancer-related fatigue is associated with side effects from treatment, pain, functional disability, sleep disturbances, mood disturbances and co-morbid conditions.4 Patients with CRF have declines in physical activity and function, which significantly impacts quality of life (QOL).5 The mechanisms underlying functional declines and fatigue in breast cancer patients are likely multifactorial, but deconditioning, sarcopenia, increases in inflammatory cytokines, insulin resistance, and changes in muscle and fat metabolism seem to play important roles.4,6
Hormone receptor-positive tumors are the most common breast cancers in postmenopausal women, and endocrine therapies, which block the production or effects of estrogen, are the mainstay of treatment in these patients. Due to their superior efficacy in postmenopausal women, aromatase inhibitors (AIs) are the standard of care for long-term estrogen suppression in these patients.7 Estrogen deprivation, however, results in multiple side effects which may worsen fatigue and the functional and metabolic declines associated with cancer treatment.8 Some of the most common side effects in women taking AIs are musculoskeletal symptoms, including arthralgias and myalgias, which promote deconditioning and sarcopenia and their associated side effects.9 Because of the prolonged use of AIs in postmenopausal breast cancer patients and the improvements in cancer-related outcomes that are observed with their use, great efforts are taken to reduce AI induced musculoskeletal symptoms (AIMSS) to maintain adherence to treatment. While multiple strategies are used to manage AIMSS, current therapies mainly focus on interventions in patients who develop symptoms (tertiary prevention) rather than primary prevention.9 Exercise interventions in breast cancer patients also improve QOL, decrease fatigue, and increase physical function and strength.10,11 Understanding the role of exercise in AI side effect prevention will allow us to translate these findings into therapy guidelines.
Dates
| Last Verified: | 10/31/2015 |
| First Submitted: | 09/26/2013 |
| Estimated Enrollment Submitted: | 09/26/2013 |
| First Posted: | 10/06/2013 |
| Last Update Submitted: | 11/24/2015 |
| Last Update Posted: | 11/25/2015 |
| Actual Study Start Date: | 10/31/2013 |
| Estimated Primary Completion Date: | 08/31/2015 |
| Estimated Study Completion Date: | 08/31/2015 |
Condition or disease
Intervention/treatment
Other: Structured Exercise
Other: Usual Care
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Structured Exercise Structured and supervised aerobic and resistance training 2 times per week | Other: Structured Exercise Structured and supervised aerobic and resistance training 2 times per week |
| Active Comparator: Usual Care Subjects will be counseled on American Cancer Society and American College of Sports Medicine physical activity and nutritional guidelines at the initiation of the study. Study participants will be contacted by a physician or nurse on weeks 2, 6, 10, and 14 to provide support and encouragement to patients. | Other: Usual Care Subjects will be counseled on American Cancer Society and American College of Sports Medicine physical activity and nutritional guidelines at the initiation of the study. Study participants will be contacted by a physician or nurse on weeks 2, 6, 10, and 14 to provide support and encouragement to patients. |
Eligibility Criteria
| Ages Eligible for Study | 40 Years To 40 Years |
| Sexes Eligible for Study | Female |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - At least mild fatigue in 2 of the 4 areas of the Piper Fatigue Scale (score ≥ 1-3) - Completion of standard surgery +/- chemotherapy for breast cancer (may undergo radiation therapy during study) - 25-OH vitamin D > 20 ng/ml - Histological evidence of stage I-III hormone receptor-positive breast cancer - Body Mass Index >/=18 and <50 kg/m2 - 40-80 years of age - Non-smoking (non smoking for at least 12 months: cigarettes, cigars, pipes - Menopause over one year (absence of menses for 12 months or greater) - Sedentary (exercise no >60 min 2 times/week) Exclusion Criteria: - Taking oral steroids, warfarin, or other medications interfering with fat metabolism that may not be safely discontinued temporarily for specific produces (i.e. for 72 hours prior) - Symptomatic heart disease, coronary artery disease, congestive heart failure, or uncontrolled hypertension (systolic blood pressure over 180 mm HG)unless medically stabilized - Participant is, in the opinion of the investigator, unable to adhere to the study protocol due to medical or orthopedic conditions that limit ability to exercise or travel to the Baltimore VA for protocol procedures - Chronic pulmonary disease (on supplemental O2) - Abnormal renal function (BUN above 40 mg/dl, Cr above 1.3 mg/dl, CrCl<60mg/dl) - Unstable lymphedema - Evidence of cancer metastases or recurrence - Anemia HCT below 30 mg/dl, platelets below 80,000/cm3 - Type 1 diabetes; insulin treatment for diabetes, poorly controlled diabetes, HgA1c>10% - Abnormal response to exercise test (ST segment depression greater than 2mm, chest pain, significant arrhythmias, extreme shortness of breath, cyanosis, exercising BP above 240/120 mm HG, or other contraindications to exercise) confirmed with further diagnostic evaluations. - Abnormal liver function - Untreated dyslipidemia with National Cholesterol ATPIII 10 year cardiac risk score greater than 10% (www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04.htm) - Metal implants or devices (i.e. pacemaker) if undergoing CT scan - History of seizures or taking anti-seizure or anti convulsion medication - Allergic to lidocaine - Mini-mental state examination below 24, dementia, or unstable clinical depression by exam |
Outcome
Primary Outcome Measures
1. Fatigue [Baseline]
2. Muscle performance (muscle strength, endurance, and function) Fatigue and Muscle Performance [16 weeks]
3. Musculoskeletal symptoms (VASpain, HAQ-DI) [16 weeks]
Secondary Outcome Measures
1. Glucose Tolerance and Inflammation [Baseline]
2. Glucose Tolerance and Inflammation [16 weeks]
