- Mary C Gainford, clinical fellow1,
- George Dranitsaris, consultant pharmacist1,
- Mark Clemons (Mark.Clemons@sw.ca), medical oncologist1
- 1Division of Medical Oncology, Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5
- Correspondence to: M Clemons
- Accepted 29 January 2005
Introduction
Breast cancer is the most common malignancy in women in North America. In 2004 there have been an estimated 215 990 new cases and 40 110 deaths.1 Unfortunately, despite adjuvant treatment, 24-60% of women will ultimately develop metastatic disease. Bone remains the most common site of distant recurrence of disease and is affected in an estimated 65-75% of women with advanced breast cancer. Of those women with bone metastases, two thirds will subsequently develop skeletal related events (box).
Bisphosphonates are an established standard of care for patients with bone metastases, and although they have been shown to have some analgesic effect, the major indication for their use is to reduce the incidence and delay the onset of subsequent skeletal related events. Despite their rapid integration into standard clinical practice many uncertainties remain with regard to their use. We review the limitations of current bisphosphonate studies and the implications these have for patients in clinical practice and direct healthcare costs.
Methods
We searched the PubMed database to identify data for this review. We used a combination of the terms “breast cancer, bone metastases, bisphosphonates” and identified the reference lists of publications. We used articles published only up to January 2005. We also identified relevant abstracts from the proceedings of major oncology conferences in 2002, 2003, and 2004.
Bisphosphonate studies
The bisphosphonates are inhibitors of osteoclast mediated bone resorption. Randomised trials comparing bisphosphonates with either a placebo or no treatment in secondary prophylaxis (in patients with breast cancer and established bone metastases) have shown that once bone metastases are present, bisphosphonates in addition to chemotherapy or hormonal therapy can significantly reduce skeletal related events (tables 1 and 2).2–13
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Studies of intravenous bisphosphonate compared with placebo or no treatment
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Studies of oral bisphosphonate compared with placebo or no treatment
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