Pre-clinical Study Suggests Nab-paclitaxel Plus Bevacizumab May hold Promise for Treating Triple Negative Breast Cancer

According to a pre-clinical study presented at the AACR 101st Annual Meeting 2010, a regimen of nab-paclitaxel (Abraxane) given in combination with bevacizumab (Avastin) may have potential in treating triple-negative breast cancer, one of the most aggressive, therapy- resistant, and highly metastatic subtypes of breast cancer. Because most currently available models do not recapitulate expression profile of triple-negative breast cancer, it is difficult to devise new treatments to target these tumors; thus, the study investigators, led by Sophia Ran, PhD, department of medical microbiology, immunology, and cell biology, Southern Illinois University School of Medicine, Springfield, Illinois, established and characterized a new model of triple-negative breast cancer to assess whether nab-paclitaxel plus bevacizumab, a regimen found to be successful in treating other metastatic cancer types, may also be effective in triple-negative breast cancer.

The investigators stably transfected HCC1806 cells with red fl uorescent protein (RFP) and Renilla luciferase to establish HCC1806-RR cells to be orthotopically implanted into mammary fat pads of immunodefi cient mice. Mice developing orthotopic HCC1806-RR tumors measuring 150 mm3 were treated with saline (control), bevacizumab at 4mg/kg twice a week for 10 weeks, intravenous nab-paclitaxel at 10 mg/kg once daily for 5 weeks, or a combination of nab-paclitaxel and bevacizumab. Tumor growth rate was monitored using calipers and metastasis was analyzed by measuring luciferase activity in the lymph nodes and lungs.

The investigators found that bevacizumab inhibited tumor growth by 0%, nab-paclitaxel by 90%, and the combination therapy by 100%. Combination therapy also reduced the incidence of lymph node and lung metastases by 50% and 87%, respectively, which was statistically significant. Half of the mice (n = 10) in the combination therapy group experienced complete regression of primary tumors and metastases at both regional and distant sites.

“This preliminary study demonstrated a high sensitivity to nab-paclitaxel plus bevacizumab, suggesting there may be a role for this combination therapy to signifi cantly improve the health outcome for patients with triple-negative breast cancer,” said Ran in a press statement. In addition, the HCC1806-RR model double-tagged with RFP and Renilla luciferase can be used to study the biology of triple-negative breast cancer and to design new approaches to treat this aggressive cancer.

AACR ABSTRACT 3852 (http://bit.ly/abBiiH)