SAN DIEGO – Bisphosphonate use to treat osteoporosis was associated with a lower risk for bone metastases in women who later were diagnosed with breast cancer and continued on bisphosphonate therapy, according to findings from a retrospective cohort study.
This protective effect of bisphosphonates against bone metastases was independent of the stage of breast cancer at the time of diagnosis, Dr. Richard Kremer reported at the meeting.
Surprisingly, the 2% of study participants who stopped bisphosphonate therapy when diagnosed with breast cancer actually had a higher rate of developing bone metastases than did never-users of the medication, added Dr. Kremer of McGill University, Montreal.
The findings were gleaned from an administrative database that included 16,669 women diagnosed with local breast cancer and 4,850 diagnosed with regional disease during 1998-2005 and followed for a median of 5 years.
Ongoing randomized, double-blind, placebo-controlled clinical trials, such as the National Surgical Adjuvant Breast and Bowel Project B-34, are expected to provide definitive answers as to whether prescribing bisphosphonates protects against bone metastases. At present, the approved indication for bisphosphonates in the setting of cancer is for pain relief and prevention of fractures in patients with known bone metastases.
Among the 2,221 women who used a bisphosphonate in the 2-year period prior to diagnosis of their malignancy, 4% developed bone metastases. Of the other 19,298 women, 6.5% developed bone metastases.
Upon adjustment for breast cancer stage, comorbid conditions, age, and socioeconomic status, using a bisphosphonate prior to diagnosis of malignancy was associated with a 22% reduction in the risk of developing bone metastases. A definite dose-response effect was evident; the longer a woman was on a bisphosphonate, the greater her reduction in risk of bone metastases.
“Our study suggests that bisphosphonate therapy for treatment of osteoporosis produces significant additional benefit in preventing an important complication of breast cancer,” he said.
There is, however, a catch: The great majority of women who took a bisphosphonate during the 2 years prior to diagnosis of breast cancer continued to do so afterwards. Roughly 10% of breast cancer patients in the study were on a bisphosphonate both before and after diagnosis of their malignancy, 20% went on a bisphosphonate only upon being diagnosed with breast cancer, and just 2% of women took a bisphosphonate only prior to their breast cancer diagnosis. Nearly 70% of subjects were never on a bisphosphonate.
Women with localized breast cancer and a documented lack of lymph node involvement had a 27% reduction in their risk of developing bone metastases if they received a bisphosphonate both before and after diagnosis of their cancer, a 45% risk reduction if they went on the medication only following diagnosis of breast cancer, and a paradoxical twofold increased risk if they were on a bisphosphonate during the 2 years prior to diagnosis and then stopped.
Women with regional breast cancer who stopped taking a bisphosphonate within 2 years prior to diagnosis had a nonsignificant 19% increased risk of bone metastases compared with women never on the medication.
In contrast, they had a 49% reduction in risk if they received a bisphosphonate both before and after their diagnosis, and the same magnitude of risk reduction if they went on the drug only after their breast cancer was detected.
Dr. Kremer disclosed that he serves on the speakers bureaus of Merck Frosst Canada and Sanofi-Aventis.