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Genes found linked to breast cancer drug resistance could guide future treatment choices
Date:1/24/2010

utcomes than those without the culprit gene signature.

However, the overexpression of the two genes did not protect laboratory-grown breast cancer cells against other classes of drugs, including paclitaxel and cisplatin, reported Richardson, Wang, and the first author, Yang Li, PhD.

"These results suggest that tumors resistant to anthracyclines may still be sensitive to other agents," said Richardson, who is also on faculty at Brigham and Women's Hospital and Harvard Medical School. "So this would be very useful as a test to help pick the therapy that's going to be most effective for these patients."

Such a tool should not be difficult to develop, she said, and could be available for clinical testing within a year or two.

It's been known that some breast tumors acquire, during the course of treatment, altered genes or chromosomes that make them resistant to many cancer drugs. But with one or two exceptions, "No tests are done before treatment begins to predict who's going to be resistant or sensitive to different compounds," says Richardson. "Most breast cancer patients are initially given the same drugs."

Exceptions include patients whose tumors are spurred by estrogen and are often less sensitive to any chemotherapy; hormonal treatment is generally prescribed in that case. Also, breast cancers found to be HER2-positive are treated with the antibody trastuzumab another example of "personalized" or tailored therapy.

In search of genetic alterations that might explain disease recurrence despite treatment with adjuvant chemotherapy in some breast cancer patients, the Dana-Farber scientists scanned the genome (all the DNA) of stored breast cancer samples from patients who had been treated according to modern guidelines, including the use of anthracyclines. The samples had been taken in the operating room during breast surgery before any drug therapy had begun and thus enabled the scientists to look for DNA alter
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert

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