In the Journals

Bisphosphonates may reduce risk for bone metastases in women with breast cancer

Show Citation

October 27, 2014

Women with breast cancer who used low-dose oral bisphosphonates for postmenopausal osteoporosis demonstrated a reduced risk for bone metastases, according to study results.

“Skeletal metastases develop in up to 70 percent of women who die from breast cancer,” researcher Richard Kremer, MD, director of the Bone and Mineral Unit at McGill University Health Centre and professor with the faculty of medicine at McGill University, said in a press release. “This causes considerable suffering and is life-threatening. Preventing this could translate into saving a significant number of lives.”

Kremer and colleagues reviewed data on 21,664 women diagnosed with breast cancer in the Province of Quebec between 1998 and 2005. Follow-up continued until 2007. Researchers stratified patients based on the presence of local (stage 0 to stage II) or regional (stage III) disease at diagnosis.

Researchers also assessed pre- and post-diagnosis exposure to bisphosphonates prescribed for prevention or treatment of postmenopausal osteoporosis. Medications studied included IV zoledronate or pamidronate, or oral clodronate.

Time to development of bone metastases served as the study’s primary outcome. All-cause mortality and DFS served as secondary endpoints.

Kremer and colleagues used Cox proportional hazards to calculate the effect of bisphosphonate use on time to onset of bone metastases.

Researchers adjusted for potential confounders, including age, comorbidity, number of ambulatory medical visits in the 2 years prior to breast cancer diagnosis, patients’ financial resources, and concomitant use of medications for bone health and cancer.

Among women with local disease at diagnosis, those who used bisphosphonates during the pre-diagnosis period but then stopped demonstrated twice the risk for bone metastases compared with those who never used bisphosphonates (HR=2.03; 95% CI, 1.26-3.26). Those who took bisphosphonates only after breast cancer diagnosis (HR=0.55; 95% CI, 0.44-0.69), as well as those who used bisphosphonates prior to breast cancer diagnosis and continued to use them post-diagnosis (HR=0.72; 95% CI, 0.53-0.98), demonstrated reduced risk for bone metastases.

Among women with regional disease at diagnosis, those who used bisphosphonates during the pre-diagnosis period but then stopped demonstrated an elevated risk for bone metastases compared with those who never used bisphosphonates (HR=1.21; 95% CI, 0.6-2.11). Those who took bisphosphonates only after breast cancer diagnosis (HR=0.51; 95% CI, 0.4-0.65), as well as those who used bisphosphonates prior to breast cancer diagnosis and continued to use them post-diagnosis (HR=0.5; 95% CI, 0.33-0.75), demonstrated reduced risk for bone metastases.

“Our study is novel in that it mainly involved women who were postmenopausal and in whom bone-turnover is high due to osteoporosis,” Kremer said. “We believe that this process results in an environment that is favorable for tumor cell growth and consequent metastasis. We know that bisphosphonates work by slowing down this bone turnover. This will, in turn, make it harder for tumor cells to establish in the bone and may explain why we saw such a decline in metastasis.”

Researchers also observed associations between bisphosphonate use and mortality.

Among women with local disease, those who used bisphosphonates prior to breast cancer diagnosis only demonstrated increased risk for all-cause mortality (HR=1.37; 95% CI, 1.07-1.76) and cancer-related mortality (HR=1.78; 95% CI, 1.18-2.68) compared with those who never used bisphosphonates. Women who used bisphosphonates only after breast cancer diagnosis (all-cause mortality, HR=0.48; 95% CI, 0.42-0.54; cancer-related mortality, HR=0.48; 95% CI, 0.39-0.59) and those who used bisphosphonates both before and after breast cancer diagnosis (all-cause mortality, HR=0.7; 95% CI, 0.6-0.8; cancer-related mortality, HR=0.48; 95% CI, 0.39-0.59) demonstrated reduced risk for mortality.

Among women with regional disease, those who used bisphosphonates prior to breast cancer diagnosis only demonstrated increased risk all-cause mortality (HR=1.44; 95% CI, 1.01-2.06) and cancer-related mortality (HR=1.04; 95% CI, 0.55-1.96) compared with those who never used bisphosphonates. Women who used bisphosphonates only after breast cancer diagnosis (all-cause mortality, HR=0.43; 95% CI, 0.36-0.51; cancer-related mortality, HR=0.44; 95% CI, 0.34-0.56) and those who used bisphosphonates both before and after breast cancer diagnosis (all-cause mortality, HR=0.76; 95% CI, 0.61-0.96; cancer-related mortality, HR=0.77; 95% CI, 0.55-1.07) demonstrated reduced risk for mortality.

The association between bisphosphonate use and improved survival merits further investigation, according to Nancy E. Mayo, PhD, researcher and professor at McGill University, said in the press release.

“Ours was an epidemiological study involving a large number of women, strengthening the importance of the findings,” Mayo said. “However, clinical interventional studies are needed before the results can be translated into standard clinical practice and guidelines.”

Disclosure: The researchers report no relevant disclosures.

itj+ Infographic

itj+ Perspective