Testing breast tumors may predict response to chemotherapy
(13 May 2009: VIDYYA MEDICAL NEWS SERVICE) -- Women treated for breast cancer whose tumors carry normal versions of the genes HER2 and TOP2A may not benefit from an anthracycline as part of additional chemotherapy designed to prevent a recurrence. Instead, these patients may benefit from a less toxic regimen that does not include an anthracycline, researchers reported online in the Journal of the National Cancer Institute on April 28.
In previous studies, the benefits of adjuvant therapy with an anthracycline-based regimen were restricted to women with HER2 alterations (about 20 percent of breast cancers). But because the TOP2A gene resides near HER2, some researchers have wondered whether the response to anthracyclines might be associated with TOP2A alterations.
To explore the question, Dr. Kathleen Pritchard of Sunnybrook Odette Cancer Centre in Toronto and her colleagues analyzed these genes in tumor samples from 438 of the 710 participants in the National Cancer Institute of Canada's Mammary 5 trial.
Women whose tumors had either TOP2A deletions or amplifications (extra copies) had longer recurrence-free survival and overall survival in response to chemotherapy that included the anthracycline epirubicin than to chemotherapy without anthracyclines, while patients with normal TOP2A genes showed no difference in responsiveness. Alterations in TOP2A and in HER2 appear to have similar value in guiding the selection of anthracycline-containing regimens, the researchers concluded, noting that larger studies are needed to determine which measurement is more closely associated with response to these regimens.
An accompanying editorial agrees that women whose tumors have normal HER2 and TOP2A genes should not receive anthracycline-based chemotherapy. The authors note that molecularly targeted drugs such as trastuzumab (Herceptin) often provide the most benefit to patients with alterations in the pathways affected by the drugs, and it now appears that the same may be true of standard chemotherapy agents.
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