CHICAGO, Illinois—Zoledronic acid (Zometa^®) may help prevent the spread of locally advanced breast cancer into the bone marrow, according to new research presented at the 2008 American Society of Clinical Oncology (ASCO) annual meeting in Chicago.¹

"Chemotherapy causes increased bone turnover, so we think that by suppressing this with zoledronic acid we create an unfavorable environment for tumor cells and, hopefully, long-term data will show that this decreases the development of metastatic disease," lead researcher Rebecca Aft, MD, PhD, an associate professor of surgery, a faculty member of the Siteman Cancer Center, and a Washington University breast surgeon at Barnes Jewish Hospital in St Louis, told MSKreport.com.

In Dr. Aft's study of 120 women with stage II/III breast cancer, those who received zoledronic acid with chemotherapy were less likely to have breast tumor cells growing in their bones after 3 months compared with those who did not receive the bisphosphonate with their chemotherapy.

"We think that zoledronic acid changes the bone marrow so that cancer cells are unable to lodge there," Dr. Aft said. In the absence of zoledronic acid, the researchers believe that the bone marrow in breast cancer patients soon harbors micrometastases and that these cells are likely to evolve into metastatic disease.

The women in the study received either zoledronic acid 4 mg intravenously every 3 weeks for 1 year, starting with their first cycle of chemotherapy, or no zoledronic acid.
At the time of diagnosis, none of the patients had evidence of metastatic disease on computed tomography and/or positron emission tomography scans. Bone marrow samples of the iliac crest showed that ~40% of the patients had micrometasteses in their bone marrow.
The researchers took bone marrow samples again 3 months and 1 year after treatment began.

Only 23% of women who received zoledronic acid had tumor cells after 3 months compared with 36% of women who did not receive the drug. The result was not statistically significant.
Of women who started with no tumor cells in their bone marrow, 88% remained free of tumor cells in their bone marrow if they took zoledronic acid, compared with 70% who did not take the drug. This result approached statistical significance. The 1-year results are not yet available, and now the team is now following the patients to 5 years.

"We found that patients who are negative for tumor cells in bone marrow have a very good chance of staying negative if they take zoledronic acid," Dr. Aft said. "If longer follow-up shows that women without tumor cells in their bones do not go on to develop metastatic disease, then it would be reasonable to say that bisphosphonates will likely benefit women with locally advanced breast cancer."

Bisphosphonates are relatively safe, so "if our results are borne out showing decreased metastatic disease, [zoledronic acid] could help all breast cancer patients not just those whose cancers are estrogen-receptor positive," Dr. Aft said. The study patients are being monitored for osteonecrosis.

It is too early to say whether other bisphosphonates would have the same effect on breast cancer metastasis, but the link between bone and the breast cancers have been associated in the past by other drugs. For example, selective estrogen-receptor modulators (SERMS) block estrogen receptors in breast cells; preventing them from multiplying. SERMS also stimulate estrogen in other areas of the body where it is not deleterious such as in the bones. SERMs stimulate bone cells and stave off osteoporosis as well as prevent breast cancer recurrence in women with estrogen receptor-positive breast cancer.

Reference

1. Aft R, Watson L, Ylagan M, et al. Effect of zoledronic acid on bone marrow micrometastases in women undergoing neoadjuvant chemotherapy for breast cancer. Presented at: 44th ASCO annual meeting; May 30-June 5, 2008; Chicago, Ill. Abstract 1021.