Submitted to: Annals of Surgical Oncology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 7/17/2008
Publication Date: 12/11/2008
Citation: Lyons, J.M., Anthony, C.T., Thomson, J.L., Woltering, E.A. 2008. A novel assay to assess the effectiveness of antiangiogenic drugs in human breast cancer. Annals of Surgical Oncology. 15(12):3407-3414. Interpretive Summary: While current chemotherapy treatment for patients with breast cancer is based upon the unique characteristics of a patient's tumor, methods that aid in drug selection are limited. Most current selection methods are based upon tumor cell growth or death. We tested a laboratory method which measures the growth of new blood vessels, a mechanism which enables tumors to grow. Of the five drugs tested, three were very effective at stopping tumor growth of new blood vessels in breast cancer. These results indicate that our method is useful in assessing the effectiveness of chemotherapy drugs for individual breast cancer tumors. Hence, our method can be used in conjunction with other methods to select the most appropriate chemotherapy treatment for patients with breast cancer.
Technical Abstract: Many cytotoxic drugs maintain antiangiogenic properties, but there are no human, tumor-based assays to evaluate their antiangiogenic potential. We used a fibrin-thrombin clot-based angiogenesis model to evaluate the angiogenic response of human breast cancer to various cytotoxic agents commonly used in its treatment. Fragments of freshly harvested human breast tumors were embedded in fibrin-thrombin clots and treated with five drugs: adriamycin, taxol, 5-fluorouracil (5-FU), methotrexate, and vincristine (n=30 explants per treatment group). Tumor fragments were tested with a single dose of each reagent. Angiogenic initiation, angiogenic growth, and overall angiogenic effect were determined for each treatment group using a previously validated scale. All four breast cancer specimens tested developed an angiogenic response, sprouting neovessels in vitro in a time-dependent fashion (r = .84, p =.0007). Taxol statistically inhibited angiogenesis in all 4 specimens with decreases in the mean angiogenic initiation, angiogenic growth, and overall effect that were 69%, 81%, and 94% of control values, respectively. Vincristine and 5-FU inhibited the mean overall angiogenic effect by 89% and 82% compared to control, respectively. Adriamycin inhibited overall effect by 49%. Methotrexate was less effective. Freshly harvested breast cancer specimens develop an angiogenic response in a fibrin-thrombin clot-based angiogenesis model and respond to treatment with antineoplastic/antiangiogenic drugs. The antiangiogenic potential of commonly used breast cancer drugs varied among individual tumors. Data obtained from this model is unique and might potentially be used to further enhance the efficacy of cytoxic regimens and individualize patient therapy.