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Existing drugs may help more breast cancer patients
Date:12/7/2012

n this modest percentage translates into more than 4,000 patients per year.

The study, led by senior author Matthew J. Ellis, MD, PhD, of Washington University, and published online Dec. 7 in the journal Cancer Discovery, analyzed data from eight DNA sequencing studies, which together included about 1,500 patients. Two of the sequencing studies were conducted by The Genome Institute at Washington University, in collaboration with study co-author Elaine R. Mardis, PhD, co-director of the genome institute.

Of the 1,500 patients, 25 were found to have HER2 mutations without gene amplification. Not all mutations appeared to have the same effect, however. After analyzing 13 of the mutations, seven were found to drive cancer growth. In the laboratory analysis, most of these mutations responded well to the anti-HER2 drugs lapatinib and trastuzumab, both approved by the U.S. Food and Drug Administration. Although two of the mutations were resistant to lapatinib in lab tests, they responded well to neratinib, a newer anti-HER2 drug that is currently in phase II clinical trials.

Bose also cautions that some mutations were found to be "silent," meaning they did not drive the tumor's growth and therefore would likely not respond to anti-HER2 drugs.

The study's findings have led directly to the launching of a phase II clinical trial to test whether patients with HER2 mutations (but not the amplification) will benefit from anti-HER2 drugs. The trial will include patients with stage IV breast cancer classified as HER2 negative. Their HER2 genes will be sequenced to look for mutations. If mutations are present, they will be treated with neratinib in addition to the standard treatment they would otherwise receive.

At Washington University, the trial will be led by Cynthia X. Ma, MD, PhD, associate professor of medicine. The other centers participating in the study are the Dana-Farber Cancer Institute, Memorial Sloan-Kettering Cance
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Contact: Julia Evangelou Strait
straitj@wustl.edu
314-286-0141
Washington University School of Medicine
Source:Eurekalert  

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