September 26, 2011

September 26, 2011 (San Diego, California) — The use of bisphosphonates prior to a diagnosis of breast cancer appears to help prevent the development of bone metastases, which can result from the disease, according to research presented here at the American Society for Bone and Mineral Research 2011 Annual Meeting.

Bisphosphonates, used widely for the treatment of osteoporosis, have antibone resorption effects that make them valuable in the treatment of osteolytic bone disease and osteolytic lesions of metastatic breast cancer, in particular.

Pamidronate, an aminobisphosphonate, has been approved for the treatment of metastatic breast cancer to bone since 1996, and the bisphosphonate clodronate has been shown in research to be effective in preventing skeletal metastasis in high-risk cancer patients when given immediately after tumor removal.

"Bisphosphonates can be useful in osteolytic bone disease, particularly in patients with breast cancer," said lead author Richard Kremer, MD, PhD, associate professor in the division of endocrinology, McGill University, Montreal, Quebec, Canada. "However, that benefit in the context of prevention has not been well established in clinical studies.

Given the benefits in skeletal metastasis, Dr. Kremer and researchers from McGill University sought to determine whether the drugs could prevent metastasis, even before the onset of breast cancer.

The cohort study consisted of 21,664 women — 77% with stage 0 or I breast cancer and 10.2% (n = 2221) who had used a bisphosphonate in the 2-year period prior to the diagnosis of breast cancer.

The most common bisphosphonates were alendronate (66%), risedronate (23%), and etidronate (11%). The age range was 50 to 64 years, and the median and maximum follow-up times were 5 and 10 years, respectively.

Among the 19,443 women who did not use bisphosphonates prior to their breast cancer diagnosis, 6.5% developed bone metastases; among the 2221 women who were treated with bisphosphonates prior to their breast cancer diagnosis, 4.0% developed bone metastases.

The unadjusted hazard ratio (HR) was 0.70 (95% confidence interval [CI], 0.57 to 0.87); with adjustments for age, socioeconomic status, comorbidities, and stage of cancer, the HR was 0.78 (95% CI, 0.63 to 0.98).

Interestingly, however, patients who were treated with bisphosphonates prior to their breast cancer diagnosis had no improvement or increased risk of developing bone metastasis if they did not continue the drugs after they were diagnosed.

"These results indicate the strong potential for bisphosphonates to be protective for the development of bone metastases when administered prior to the diagnosis of breast cancer, independent of stage of disease at diagnosis," the authors write.

Dr. Kremer noted that the study was adjusted for the different types of cancer radiation and chemotherapies.

He added that the study supports Paget's seed and soil hypothesis — in which a favorable terrain, such as the bone microenvironment, helps the seeds, or cancer cells.

"Bisphosphonates are known to deactivate the terrain, and therefore make cancer cells less susceptible to settle and grow into bone," he explained.

Despite the promising results, more rigorous studies are needed to prove a benefit from bisphosphonate use on bone health if breast cancer is later diagnosed, said Rowan T. Chlebowski, MD, PhD, professor of medicine at the David Geffen School of Medicine at the University of California at Los Angeles (UCLA) and chief of the division of medical oncology and hematology at the Harbor–UCLA Medical Center.

"The analyses did not control for bone mineral density differences [or] potential adjuvant therapy differences, including whether tamoxifen or aromatase inhibitors were used," he said.

"The finding provides a signal that bisphosphonates may play a role in early cancer management, but it is not definitive. There are randomized trials that may eventually answer those questions."

Dr. Kremer reports being on the speakers bureaus for Merck Frosst Canada and Sanofi-Aventis. Dr. Chlebowski reports receiving grants for clinical research from Amgen; serving as an advisor or consultant for Amgen, AstraZeneca, Novartis, and Pfizer; and serving as a speaker or a member of a speakers bureau for AstraZeneca and Novartis.

American Society for Bone and Mineral Research (ASBMR) 2011 Annual Meeting: Abstract 1100. Presented September 18, 2011.


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