Abstract
BackgroundDenosumab inhibits the receptor activator of nuclear factor κB (RANK) pathway and is used to treat osteoporosis. Emerging evidence suggests RANK-blockade may play a role in mammary tumourigenesis. Thus, we undertook a population-based study of denosumab use and breast cancer risk in a large cohort of postmenopausal women.MethodsWe included women 67+ years with prior bisphosphonate use who filled a first prescription for denosumab. They were matched on age, date, cumulative prior use of and time since last use of a bisphosphonate to women with no history of denosumab. Cox proportional hazards was used to estimate the hazard ratio (HR) of breast cancer with denosumab use.ResultsA total of 100,368 women were included in the analysis with 1271 incident breast cancer events. Denosumab use was associated with a 13% decreased breast cancer risk (HR = 0.87; 95% CI 0.76–1.00). There was no relationship between increasing number of denosumab doses and breast cancer risk (P-trend = 0.15).ConclusionThese findings suggest a potential protective effect of ever denosumab use on breast cancer risk in a cohort of older women previously treated with bisphosphonates.
Highlights
The drug denosumab is an anti-RANKL monoclonal antibody which is used to treat osteoporosis and prevent skeletal damage caused by breast cancer metastases.[1]
1422 demographic information; the Ontario Cancer Registry (OCR)[16] to identify invasive breast cancer and cancer history; the Canadian Institute for Health Information Hospital Discharge Abstract Database (CIHI-DAD/) for information regarding hospital admissions; the National Ambulatory Care Reporting System (NACRS) for emergency department visits and day surgeries; the Ontario Drug Benefit (ODB) database for prescription drug claims records as all residents of Ontario aged 65 years and older are eligible for provincial drug coverage through the ODB;[17,18] and the Ontario Health Insurance Plan (OHIP) for information about physician service claims including mammography history
Study eligibility Given that eligibility for ODB coverage of denosumab is predominantly restricted to women with a history of oral bisphosphonate use, and breast cancer risk is suggested to be lower among women with osteoporosis and following bisphosphonate exposure;[19,20,21] we restricted inclusion to women with prior oral bisphosphonate use to isolate effects of denosumab
Summary
The drug denosumab is an anti-RANKL monoclonal antibody which is used to treat osteoporosis and prevent skeletal damage caused by breast cancer metastases.[1] RANK (receptor activator of nuclear factor κB) and its ligand (RANKL) are known for their involvement in bone metabolism.[2] Binding of RANKL to RANK on osteoclast precursors induces osteoclast maturation and activation, thereby stimulating bone resorption. Denosumab inhibits the receptor activator of nuclear factor κB (RANK) pathway and is used to treat osteoporosis. METHODS: We included women 67+ years with prior bisphosphonate use who filled a first prescription for denosumab. CONCLUSION: These findings suggest a potential protective effect of ever denosumab use on breast cancer risk in a cohort of older women previously treated with bisphosphonates
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