Julie Gralow, MD & Peggy Porter, MD
Southwest Oncology Group,
University of Washington and
Fred Hutchinson Cancer Research Center, Seattle, WA

A new SWOG project will examine metastases involving the bone, common in advanced breast cancer patients. Bone is the first site of distant recurrence in 25-40% of metastatic breast cancer cases. There is a synergistic interaction between the bone environment and breast cancer cells that enables bone cells to stimulate the growth and survival of breast cancer cells that migrate to the area. Bisphosphonates are a class of drugs that have a strong effect on bone, with their primary role being to inhibit the action of a type of bone cells called osteoclasts that are associated with bone breakdown. Bisphosphonates have been shown to strengthen bones in patients with osteoporosis, and in low doses are frequently used for this indication. In high doses, bisphosphonates have been shown to reduce bone destruction and improve bone symptoms in advanced breast cancer patients with bone metastases. Small studies from Europe suggest that it is possible that these agents can also reduce and/or prevent the later occurrence of bone metastases when given to newly diagnosed, early stage breast cancer patients. A large, randomized, 6,000-patient multi-center trial (SWOG S0307) is currently ongoing to determine whether adjuvant bisphosphonates can prevent bone metastasis and improve survival in early stage breast cancer patients. It will be important to determine what risks are involved in the use of high-dose bisphosphonates in this setting. Companion studies will look at the effect that high dose bisphosphonates have on bone quality and quantity by using bone biopsies, bone density scans, and blood and/or urine markers of bone turnover. The researchers hope to determine if long term use of high doses of bisphosphonates has a detrimental effect on bone.