Exercise to Prevent Aromatase Inhibitor Side Effects in Breast Cancer Patients (BCS2)

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.