bisphosphonates to prevent (and not just treat) bone mets

[Lani]

not specifically done in a her2 like tumor, but of interest:

Bisphosphonates Inhibit Cancer in Animal Model


NEW YORK (Reuters Health) Mar 05 - Bisphosphonates inhibit the growth of breast cancer bone metastases in a mouse model, according to a report in the February 21st Journal of the National Cancer Institute.

Previous research has shown that bisphosphonates can reduce skeletal tumor burden and inhibit the formation of bone metastases in animal models, the authors explain. They also inhibit the proliferation of various human tumor cell lines in vitro.

Dr. Philippe Clezardin from Faculte de Medecine Laennec, Lyon, France and his associates investigated the effects of zoledronic acid and clodronate on osteolysis and skeletal tumor growth in a mouse model of bone metastases of human breast cancer.

Treatment with bisphosphonates, beginning 18 days after tumor cell injection, significantly reduced the size of osteolytic lesions, the authors report, while preventing bone loss and decreasing skeletal tumor burden.

Pretreatment with bisphosphonates was effective in reducing osteolytic lesions and improving bone mineral density only when daily or weekly regimens were used (as opposed to a single dose), the researchers note.

Similarly, daily or weekly bisphosphonate treatment, but not single-dose treatment, significantly reduced the homing of tumor cells to bone marrow, the report indicates.

"Our results show that clinically relevant doses of bisphosphonates produced meaningful antitumor effects in an animal model of breast cancer bone metastasis, as long as the bisphosphonate was administered at a low dosage on a daily or weekly dosing schedule," the authors conclude.

The findings "also suggest that, in the clinical setting, bisphosphonate therapy with a long dosing interval could reduce osteolysis by inhibiting bone resorption, whereas therapy with a more frequent dosing interval could also directly affect the growth of tumor cells resident in bone."

"On the basis of our preclinical results reported here and those obtained for clodronate and for dose-dense chemotherapy in clinical trials," the investigators continue, "we anticipate that the use of dose-dense bisphosphonate therapy as adjuvant treatment of primary breast cancer will decrease the risk of bone metastases."

J Natl Cancer Inst 2007;99:322-330.