Bone drug may prevent breast cancer spread

ST. LOUIS – Cancer Digest – The osteoporosis drug, zoledronic acid may prevent metastatic breast cancer when given before surgery, say researchers. Led by Dr Rebecca Aft, of the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, the research team found that fewer women in their study who were given the drug in addition to chemotherapy had breast cancer cells in their marrow at the time of surgery to treat the breast cancer, compared to women who only underwent chemotherapy prior to surgery. Such cells are called disseminated tumor cells, or DTCs. Their findings appear in the May issue of The Lancet Oncology.These are breast cancer cells taken from a patient's bone marrow. The cancer cells are stained to make them easy to spot among the normal cells of the bone marrow.		These are breast cancer cells taken from a patient's bone marrow. The cancer cells are stained to make them easy to spot among the normal cells of the bone marrow.

"Bone marrow seems to be a DTC sanctuary, allowing them to adapt and disseminate to different organs, where they're a leading cause of death," says study leader Rebecca Aft, MD, PhD, associate professor of surgery and a breast cancer specialist at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. "We believe that zoledronic acid inhibits the release of growth factors that help support the growth of DTCs."

Every day, tumors shed thousands of cells, which spread throughout the body sometimes starting new tumor sites, called metastases. Breast cancer cells often lodge in bone marrow where bone growth factors help them survive according to the researchers.

Chemotherapy can stimulate bone turnover which is the process of replacing old bone cells with new cells. The bone growth factors released in this process can potentially exacerbate the problem of disseminated cancer cells in the bone, which can resurface later to cause metastatic disease in cancer patients.

Zoledronic acid belongs to a family of drugs called bisphosphonates used to treat brittle bones, or osteoporosis in postmenopausal women. It is also prescribed for other disease. It is marketed under the brand names Zometa® and Reclast®.

In this randomized phase II clinical trial, researchers randomly assigned 109 women with newly diagnosed stage II or stage III breast cancer to two treatment groups. The control group received chemotherapy alone, while the other received a combination treatment of chemotherapy and zoledronic acid.

After three months the researchers found that the number of women with breast cancer cells in their bone marrow decreased from 43 percent to 30 percent in the combination group, compared with a decrease from 48 percent to 47 percent in the comparison group. While this difference suggest the drug was affecting the dissemination of cancer cells, it wasn't a large enough difference to confirm that the result was due to the drug alone.

The researchers also found that of those patients who had no breast cancer cells in their bone marrow at the start of the study, 87 percent remained negative after three months of combination treatment compared to 60 percent of those who received chemotherapy alone, a result that was statistically significant.

Zoledronic acid treatment with chemotherapy had additional benefits. Women in the combination group experienced significant gains in bone density after 12 months. This is helpful for breast cancer patients, who often develop osteoporosis as a side effect of chemotherapy and other breast cancer treatments.

The study also suggested that zoledronic acid may help fight certain types of breast tumors directly. Aft speculates that the drug may stop the tumor from making its own blood supply, modify the immune system in a way that makes it harder for tumor cells to survive or even cause the cancer cells to commit suicide.

"Although it's common practice to administer zoledronic acid during chemotherapy given after breast cancer surgery, it isn't common when chemotherapy is given before surgery," Aft says. "Because chemotherapy increases bone loss, we would argue that women should receive zoledronic acid at the time of chemotherapy in the presurgical setting. Our single-institutional study also suggests that similar protocols using zoledronic acid for high-risk breast cancer patients should continue to be tested in larger, multi-institutional studies."