An abnormality in two genes can make a common class of chemotherapy drugs used to fight breast cancer less effective, U.S. researchers said on Sunday in a finding that could help doctors better tailor treatments.
They said changes in two genes on a small region of chromosome 8q made tumors resist the effects of drugs called anthracyclines, but not other types of chemotherapy drugs.
"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.
"This can potentially be used to help guide therapy on a more personalized way based on a patient's own tumor. That's why it's exciting," Richardson said in a telephone interview.
She said it may be possible to develop a genetic test to better tailor treatments to a patient's individual tumor.
Doctors already can test for certain genes to tell whether a woman's breast cancer is sensitive to estrogen, making her a candidate for hormone-blocking drugs such as tamoxifen.
Breast cancer patients whose tumors generate a protein called HER-2, which can fuel cancer growth, are often treated with Herceptin, or trastuzumab, a drug developed by Genentech, now a unit of Roche Holding AG.
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 Richardson said there were no tests to help doctors 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, Richardson, colleague Zhigang Charles Wang and others studied the DNA of breast tumor samples taken from 85 patients before they had any chemotherapy.
In tumors that turned out to be drug-resistant, the team found a region on chromosome 8 that had many extra or amplified copies of DNA stretches.
When two genes in this region called LAPTM4B and YWHAZ were overexpressed — working too hard — the tumors were resistant to anthracycline drugs.
Tests on cells in the lab confirmed that.
Using data from a Belgian study in which breast cancer patients were first treated with chemotherapy drugs including anthracyclines before their tumors were removed, 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," Richardson said.
Richardson said the team was 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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