Bisphosphonates May Prevent Postmenopausal Breast Cancer Skeletal Metastasis

Osteoporosis medication may reduce the risk of postmenopausal breast cancer spreading to the bones

medwireNews: Bisphosphonate use may protect against the development of postmenopausal breast cancer skeletal metastases, say researchers who found the osteoporosis treatment may benefit women with both early and advanced disease.

Bisphosphonate use is already known to delay further skeletal events in breast cancer patients with bone metastases but this is among the first studies to show a preventive role for women taking low doses for osteoporosis, explain Richard Kremer, from McGill University in Montreal, Quebec, Canada, and co-workers.

“An association between bisphosphonate use and improved survival was also observed and merits further investigation”, they write in the Journal of the National Cancer Institute.

Overall, 25% of the 21,664 women in a breast cancer cohort used bisphosphonates, including 29.8% of the 16,669 patients with local disease and 20.9% of the 4850 women with regional disease.

Bisphosphonates were used before diagnosis, after diagnosis and in both time periods by 1.3%, 19.0% and 9.6%, respectively, of the women with stage 0 to II breast cancer with corresponding values of 2.4%, 12.2% and 6.4% of those with stage III cancer.

Bone metastases occurred in 4.5% of the patients with local disease, affecting 5.0% of patients who did not use bisphosphonates versus 8.5%, 2.8% and 3.0% of patients who used bisphosphonates before diagnosis, after diagnosis and in both periods, respectively.

In addition, 14.2% of patients with regional disease developed bone metastases, including 15.8% of those who did not use bisphosphonates and 15.1%, 9.6% and 7.5% of patients taking the drugs before, after and throughout the study period, respectively.

After adjusting for age, comorbidity and other confounding factors, the hazard ratio (HR) for bone metastases with prediagnostic bisphosphonate use versus no use was 2.03 for patients with local disease and 1.21 for those with regional disease. The corresponding HRs for overall mortality were 1.37 and 1.44 and for cancer-related mortality were 1.78 and 1.04.

For postdiagnostic bisphosphonate use versus no use, the HRs for bone metastases in local and regional disease patients were 0.55 and 0.51, respectively, with overall mortality HRs of 0.48 and 0.43 and cancer-related mortality HRs of 0.48 and 0.44.

And, for bisphosphonate use both before and after breast cancer diagnosis, the HRs for bone metastases in local and regional disease patients was 0.72 and 0.50, respectively, with overall mortality HRs of 0.70 and 0.76 and cancer-related mortality HRs of 0.66 and 0.77.

“The main difference between our study and the previous trials is that our bisphosphonate treated group, 25% to 30% of the study population, would likely have had had low bone mass (osteopenia or osteoporosis) and high bone turnover. In fact, 92% (prediagnosis) and 95% (postdiagnosis) of women had had a bone mineral density test overlapping in time with bisphosphonate prescription”, the authors explain.

“This suggests that the risk reduction is strongest in the group with the most vulnerable bones.”

They therefore add: “An urgent area of further clinical and research development would be to evaluate the effect of bisphosphonate considering bone status.”


Kremer R, Gagnon B, Meguerditchian A, et al. Effect of oral bisphosphonates for osteoporosis on development of skeletal metastases in women with breast cancer: Results from a pharmaco-epidemiological study. JNCI 2014; Advance online publication 2 October. doi: 10.1093/jnci/dju264

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