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Genes Predict Who Responds to Breast Cancer Chemo
Certain gene patterns fare better than others

By Amanda Gardner
HealthDay Reporter

(HealthDay is the new name for HealthScoutNews.)

THURSDAY, July 31 (HealthDayNews) -- The genetic profile of a woman's breast cancer tumor could determine how well she responds to chemotherapy.

A preliminary study, reported in the Aug. 2 issue of The Lancet, found that patterns of gene expression could predict how women reacted to docetaxel, a new and widely used chemotherapy drug. The study was partially funded by Aventis, which makes docetaxel.

A finding such as this, if validated, could radically alter the treatment landscape for this type of cancer.

"This is not a new idea certainly. It's a rather self-evident sort of experiment that many people are doing in many different cancer contexts," says Jeff Boyd, director of the Gynecology and Breast Cancer Research Laboratory at Memorial Sloan-Kettering Cancer Center in New York City.

But, he adds, "this is, to my knowledge, the first study to look specifically to response at chemotherapy in breast cancer with a nice sort of positive result." Boyd's lab is doing similar research with ovarian cancer.

Because chemotherapy drugs boost survival rates so much, women routinely receive them (or hormonal treatments) after surgery. While clinicians have a test to tell which women will respond to hormonal treatment, they don't yet have a way to distinguish which women will respond to specific chemotherapy regimens, something which has led to a sort of one-size-fits-all approach.

"It once was thought that surgery alone cured most women of breast cancer and that unpleasant and toxic chemotherapy after breast cancer surgery was only necessary for the minority of women whose tumors had obviously spread," Dr. Peter O'Connell, the senior author of the Baylor College of Medicine study, says in a prepared statement.

O'Connell, who is now chairman of the human genetics department at Virginia Commonwealth University, adds, "But it turned out that one third of the women who didn't have chemotherapy had recurrences of cancer. So now most patients with operable breast cancer undergo different forms of chemotherapy to kill any cancer cells that might have spread."

"The current standards in breast cancer are all based on large phase 3 clinical trials that have shown survival regimens with a particular regimen," Boyd says. The most effective right now is a combination of three drugs, one of which is docetaxel or a related drug, the study notes. If doctors knew beforehand who would respond positively to a certain therapy, they would gain precious treatment time.

From September 1999 to June 2001, researchers at Baylor, in Houston, took samples from the breast tumors of 24 women before surgery or any other kind of treatment. The women then each received four cycles of docetaxel. The researchers recorded the clinical staging and size of the tumors at every cycle and then at the end of all four cycles.

At the end of the chemo cycle, the researchers divided the women into two, more-or-less equal groups: those whose tumors were sensitive (had responded to docetaxel) and those whose tumors were resistant (had not responded as well).

Of the 24 patients (admittedly, a very small group), 11 (46 percent) were considered sensitive, while 13 (54 percent) were considered resistant.

The response of a tumor to chemotherapy is essentially considered a surrogate for survival. Previous studies have shown patients whose tumors respond to chemotherapy before surgery have a better overall outcome than those whose tumors are resistant.

Using microarray technology, the researchers did a gene analysis and found that, indeed, women with different gene expression profiles had had different responses to the drug. Specifically, tumors that had responded to treatment had a higher expression of genes involved in the cell cycle, protein transport and protein modification.

In all, the researchers ended up with a panel of 92 genes which correlated to response to docetaxel. This gene group positively predicted who would respond to chemotherapy 92 percent of the time and predicted who wouldn't respond 83 percent of the time.

"The genetic bar code is hard-wired into the tumor before treatment, so doctors can rely on the original breast tumor for the answers about chemotherapy and other questions about optimal treatment strategies, regardless of whether or not the tumor has spread," O'Connell says in his statement.

The idea would be to eventually use this gene profile to develop a test which could tell you how the patient was going to respond to a particular drug.

"It would be a rather sophisticated test in that it would involve multiple genes," Boyd says. "You would put the genes onto a custom microarray chip, rather than having whole genome or a large section of genome. You would take the patient's sample and send it to pathology and the result would be obtained in a very similar fashion to what was obtained here."

But all this, of course, is dependent on what future studies turn up.

In fact, breast cancer activists caution against overselling the research before it becomes available to patients.

And even Boyd has caveats.

"These are very promising results and the study illustrates proof of concept, that this type of approach is likely to be useful in predicting response to therapy," he says. "Any study like this is at best promising and needs desperately to be validated with an independent group of patients, preferably a larger group of patients."

More information

For more on treatment for breast cancer, visit the National Cancer Institute. The American Cancer Society has information on docetaxel.



Copyright © 2002 ScoutNews, LLC. All rights reserved.

SOURCES: Jeff Boyd, Ph.D., director, Gynecology and Breast Cancer Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York City; Aug. 2, 2003, The Lancet

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