Tumor Response Signature to Bevacizumab Recognized in HER2-Negative Breast Cancer

Surabhi Dangi-Garimella, PhD

Led by physicians at Case Western Reserve University, a collaborative team of researchers have been able to identify a gene signature that can predict how HER2-negative breast cancer patients would respond to treatment with bevacizumab, information that can prove extremely useful in making regimen changes.

For the study, researchers collected tumor biopsies from breast cancer patients who were enrolled in 2 preoperative clinical trials. Tumor samples were collected from each patient at baseline and after 1 dose of bevacizumab (HER2-negative), trastuzumab (HER2-positive), or nab-paclitaxel. RNA sequencing of the tumor samples at baseline of the HER2-negative patients identified a significant correlation between the basal-like subtype and pathologic complete response (pCR) to chemotherapy plus bevacizumab (P ≤ 0.0027), the authors write in their article published in the International Journal of Cancer. However, it was not specific enough to predict response. A single dose of bevacizumab, however, resulted in significant downregulation of TGF-β activity in every HER2-negative tumor that had achieved pCR, they found.

Based on their results, the authors conclude that modulation of the TGF-β pathway following a brief exposure to bevacizumab could be an early functional readout of pCR to preoperative anti-angiogenic treatment in the HER2-negative patient population.

“We have identified a signature that tells us which patients are likely to respond to bevacizumab and chemotherapy,” said lead investigator and senior author Lyndsay Harris, MD, professor of Medicine at Case Western Reserve, “and we can identify those patients within 15 days of the very first dose they receive. While we have found this signature to be specifically useful in response to bevacizumab, it may be useful in predicting response to other anti-angiogenic agents as well and should be tested.”
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