Gene discovery may help guide breast cancer care

CHICAGO (Reuters) - An abnormality in two genes can make anthracyclines less effective against breast cancer, U.S. researchers said on Sunday in a finding that could help doctors better tailor treatments.

They said two polymorphisms in a small region of chromosome 8q made tumors resist the effects of anthracyclines but not other types of chemotherapy agents.

"This is useful because it helps select who might be resistant to anthracyclines," said Dr. Andrea Richardson of the Dana-Farber Cancer Institute in Boston, whose study appears in the journal Nature Medicine.

Last month, a study presented at the American Association for Cancer Research San Antonio Breast Cancer Symposium found that a gene-based test called Oncotype DX made by Genomic Health Inc helped identify women who are not likely to benefit at all from chemotherapy.

But as Dr. Richardson pointed out, there are no tests to help sort out which chemotherapy drug is best to use after surgery.

"In breast cancer, most patients get two or three types of chemotherapy and every patient gets basically the same thing. Those drugs have their own toxicities. It would be great if we could not give something that is going to be toxic and not effective," she said.

For the study, Dr. Richardson, colleague Dr. Zhigang Charles Wang and others studied the DNA of breast tumor samples obtained from 85 patients in advance of chemotherapy.

In tumors that turned out to be drug-resistant, the team found a region on chromosome 8 that had many amplified copies of DNA stretches. When two genes in this region -- LAPTM4B and YWHAZ -- were overexpressed, the tumors were resistant to anthracyclines.

Using data from a Belgian study in which breast cancer patients were treated with chemotherapy, including anthracyclines, before surgery, the team accurately predicted that patients who had the abnormal gene signature would fare poorly with anthracycline drugs.

"We were able to test in a blinded way. The expression level of those genes predicted who would be resistant to the anthracycline. That validated the finding in a very direct way," Dr. Richardson said.

The team is now testing three different approaches to developing a genetic test for this problem.

"Hopefully, we'll be able to develop an assay within the next year or so. We'd need to test it in a larger number of patients to confirm that our findings hold up," she said.

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