Overview of the use of osteoclast inhibitors in early breast cancer
- Catherine Van Poznak, MD
Catherine Van Poznak, MD
- Associate Professor Department of Internal Medicine
- University of Michigan
Breast cancer is the most common female cancer worldwide. The prognosis of fully treated early breast cancer is usually very good, in part due to systemic therapies reducing the risk of recurrence. For example, in the United States, estimates are that over 89 percent of patients will survive five years or more following their initial diagnosis . Therefore, the long-term toxicities of breast cancer therapies need to be considered. (See "Adjuvant chemotherapy for HER2-negative breast cancer" and "Adjuvant systemic therapy for HER2-positive breast cancer" and "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer".)
Systemic therapies used to treat early breast cancer can be associated with loss of bone mineral density (BMD) and increased risk of osteoporotic fractures. Bisphosphonates and denosumab are potent inhibitors of osteoclast activity. They are US Food and Drug Administration (FDA)-approved for managing osteoporosis and bone metastases from a variety of malignancies, aid in preventing therapy-related bone loss, and complement nutritional (calcium and vitamin D), exercise, and healthy lifestyle behaviors.
This topic will review the use of bisphosphonates and denosumab for preservation of BMD in the adjuvant breast cancer setting. Adjuvant anticancer treatment modalities of breast cancer, methods to assess risk of fracture (eg, using history, physical exam, algorithms such as the fracture risk assessment tool [FRAX]), imaging BMD, optimal intake of calcium and vitamin D, and the utility of osteoclast inhibitors in the management of breast cancer bone metastases are reviewed elsewhere. (See "Osteoporotic fracture risk assessment" and "Screening for osteoporosis" and "Calcium and vitamin D supplementation in osteoporosis" and "Prevention of osteoporosis", section on 'Minimizing bone loss' and "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors".)
It is of note that not all pharmacologic interventions available for management of bone health may be appropriate for patients with a history of breast cancer. In general the estrogen-like, estrogen-progesterone, and parathyroid hormone therapies are to be avoided due to the potential to have negative impacts on cancer outcomes . The novel sclerostin-targeting therapies have not yet been studied in patients with a history of breast cancer and there is theoretical concern regarding the use of this class of drug in patients who may have occult bone metastases [3,4].
BREAST CANCER THERAPY-ASSOCIATED BONE LOSS
Women with a history of breast cancer may be at increased risk of osteoporosis secondary to the systemic therapies administered [5-9]. Osteoporosis is associated with an increased risk of fracture and can be associated with significant morbidity, mortality, disfigurement and loss of self-esteem, and health care expenditure .
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- BREAST CANCER THERAPY-ASSOCIATED BONE LOSS
- Premenopausal women
- Postmenopausal women
- PREVENTION OF TREATMENT-RELATED BONE LOSS
- Premenopausal women with treatment-related bone loss
- Postmenopausal women with treatment-related bone loss
- IMPACT ON BREAST CANCER OUTCOMES
- - Efficacy
- - Is there a preferred adjuvant bisphosphonate?
- - Efficacy
- TOXICITY ASSOCIATED WITH OSTEOCLAST INHIBITORS
- CLINICAL TRIALS
- SUMMARY AND RECOMMENDATIONS