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Antiangiogenic Breast Cancer Treatment May Benefit Only Patients with Well-Perfused Tumors

A Massachusetts General Hospital (MGH) research team, in collaboration with investigators at the Dana-Farber Cancer Institute, may have found a reason why the use of antiangiogenesis drugs - which has improved outcomes for patients with several types of cancer - fails to benefit some breast cancer patients. In their report, published in the journal PNAS, the investigators describe how preoperative treatment with the antiangiogenic drug bevacizumab primarily benefited patients whose tumors were highly perfused with blood vessels prior to treatment.

"As expected, bevacizumab treatment did reduce pressure within tumors and the density of tumor vasculature, but the pathologic response to therapy - whether or not it actually eradicated the tumor - appears to depend on the microvascular density of the tumor before treatment," says Rakesh K. Jain, PhD, director of the Steele Laboratory of Tumor Biology in the MGH Radiation Oncology Department and co-senior author of the current report. "In other words, our results indicate that a significant percentage of breast cancers do not have a blood supply sufficient to benefit from the vascular normalization provided by antiangiogenic drugs."

Antiangiogenesis drugs, which suppress the action of factors inducing the formation of blood vessels, have had beneficial results in treating several types of cancer; but studies of their use in breast cancer treatment have had inconsistent results. Exactly how antiangiogenesis drugs produce their effects is unclear, with one hypothesis proposing that they starve tumors of a blood supply and the other that they actually improve the delivery of oxygen to the tumor - which is required for the beneficial effects of radiation and chemotherapy - by "normalizing" the disorganized vessels that usually develop in and around tumors. Imaging studies have supported the latter theory, first proposed by Jain, but have not yet been conclusive.

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