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Denosumab and breast cancer risk in postmenopausal women: a population-based cohort study

Giannakeas V, Cadarette SM, Ban JK, Lipscombe L, Narod SA, Kotsopoulos J. Br J Cancer. 2018; 119(11):1421-7. Epub 2018 Nov 13.

Background — Denosumab 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.

Methods — We 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.

Results — A 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).

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.