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Gene alterations associated with response to anthracycline therapy for breast cancer
Date:4/28/2009

Alterations in the topoisomerase II alpha (TOP2A) gene were associated with better patient outcomes following anthracycline-based therapy compared with non-anthracycline-based regimens, according to a study in the April 28 online issue of the Journal of the National Cancer Institute. The increased responsiveness is similar to what is seen in patients whose tumors carry an amplification of the HER2 gene.

Several studies have shown that women whose tumors have amplified HER2 derive benefit from regimens that include anthracyclines, such as epirubicin and doxorubicin, while patients whose tumors lack such alteration do not. Scientists have hypothesized that this difference could be due to alterations in the TOP2A gene, which resides adjacent to HER2 on the chromosome and is often included in the stretch of amplified DNA. TOP2A is a major target of anthracycline.

To determine whether the difference in responsiveness is due to TOP2A, Kathleen I. Pritchard, M.D., of the University of Toronto, and colleagues re-analyzed data from the randomized Mammary 5 trial, conducted by the National Cancer Institute of Canada Clinical Trials Group. This trial compared an anthracycline-containing regimen (cyclophosphamide, epirubicin, and 5-fluorouracil; CEF) with a non-anthracycline-containing regimen (cyclophosphamide, methotrexate, and 5-fluorouracil; CMF) in 710 breast cancer patients. The investigators were able to analyze tumor samples from 438 patients for alteration of the TOP2A gene.

Women whose tumors carried TOP2A gene alterations had 65 percent better relative relapse-free survival and 67 percent better relative overall survival when treated with CEF compared with CMF. The differences were statistically significant. By contrast, women whose tumors were TOP2A-normal had a similar response to the two regimens. The added benefit detected for the women with TOP2A-
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Contact: Steve Graff
jncimedia@oxfordjournals.org
301-841-1285
Journal of the National Cancer Institute
Source:Eurekalert

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