Oral Bisphosphonates Tied to Lower Risk of Skeletal Metastasis from Breast Cancer
By Will Boggs MD
NEW YORK - Women who use oral bisphosphonates for prevention or treatment of osteoporosis have a reduced risk of skeletal metastasis from breast cancer, researchers from Canada report.
"There is mounting evidence to support a beneficial role of low dose bisphosphonates in a subset of breast cancer patients with high bone turnover," Dr. Richard Kremer from McGill University Health Center in Montreal, Quebec, told Reuters Health by email.
"Early therapy would cut the risk of bone metastases and improve survival by about 50% and would save many lives since the majority of women in this age group are not currently receiving bisphosphonate therapy," Dr. Kremer said.
A recent meta-analysis suggested that bisphosphonate use could reduce the risk of bone metastases by 21% in all women with breast cancer and by 35% in postmenopausal women.
Dr. Kremer and colleagues used data from more than 21,600 women in Quebec diagnosed with breast cancer to estimate the extent to which oral bisphosphonates might stave off bone metastases.
Only about a quarter of the population used bisphosphonates, and most of the use was post-diagnosis only, the team reports in the Journal of the National Cancer Institute, online October 10.
Overall, the incidence of bone metastases was 4.5% among women with local disease and 14.2% among women with regional disease.
Women with local disease who did not take bisphosphonates had a 5% incidence of bone metastases with a median time to occurrence of 33 months. Taking bisphosphonates post-diagnosis was associated with a bone metastasis incidence of 2.8% and a longer median time to occurrence of 45 months.
Women who took bisphosphonates pre-diagnosis and then stopped had a higher rate of metastases (8.5%) and a shorter median time to occurrence (15 months), however.
After adjusting for other factors, taking bisphosphonates post-diagnosis was associated with a 45% reduction in bone metastases. And continuing bisphosphonates that were started pre-diagnosis was associated with a 28% reduction in bone metastases in women with local disease. Stopping bisphosphonates that had been prescribed pre-diagnosis appeared to double the risk of developing bone metastases.
In women with regional disease, post-diagnosis use of bisphosphonates provided almost a 50% reduction in bone metastasis risk, regardless of pre-diagnosis use.
Among women with local disease, there was a dose-dependent relationship, such that every increased decile of bisphosphonate use was associated with a 4% reduction in bone metastasis risk.
"The message is that post-menopausal women with breast cancer and osteoporosis/osteopenia (the group of women that we investigated) are more likely to benefit from prevention therapy with regular treatment normally administered for osteoporosis," Dr. Kremer said. "These women are the ones at risk because their bone turnover is high which favors the development of tumor cells within bone."
"Additionally women with high bone turnover (recently menopaused) but without any sign of osteopenia/osteoporosis would likely benefit from this prevention therapy as well as pre-menopausal women receiving anti-hormonal therapy," Dr. Kremer said. "In other words, not all women with breast cancer could in theory benefit from such treatment but the ones with high bone turnover would be particularly at risk. This indeed should be tested in a new cohorts of breast cancer patients stratified according to these criteria."
"The results should still be looked at with caution since association studies such as this one do not prove causality," he stressed. "A large international multicenter clinical trial would be the next logical thing to do."
Unfortunately, Dr. Kremer added, such a trial is now unlikely to be launched by a drug company, because all the bisphosphonates are off patent.
"Only a large multinational effort supported by major funding agencies in North America and Europe could potentially revisit this very important public health problem," he said.
Dr. Robert Coleman from Sheffield Cancer Research Centre in England recently coauthored a meta-analysis that reached similar conclusions.
"Do not stop a bisphosphonate if a patient develops breast cancer," he advised in an email to Reuters Health. "The risk-benefits of adjuvant bisphosphonates are further tipped in favor of treatment and should be considered in postmenopausal women at significant risk for recurrence, e.g., bad enough to need chemotherapy."
"Additionally, for women on an aromatase inhibitor, the double benefit of prevention of bone loss and probable reduced metastasis is a strong argument for use," Dr. Coleman said.
SOURCE: https://bit.ly/1tgQa7C
J Natl Cancer Inst 2014.
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