HOUSTON — In a step toward personalized medicine, researchers in Houston are using tumor "gene screens" to predict which women with breast cancer will respond to a particular chemotherapy treatment.
Researchers at the University of Texas M.D. Anderson Cancer Center and Baylor College of Medicine reported at a cancer conference Sunday that DNA chips helped them identify gene patterns in the diseased tissue sensitive to chemotherapy. The two schools' researchers tested different treatments in separate studies.
"If these results hold up in larger validation studies, it can fundamentally change the way chemotherapy is selected for patients," said Dr. Lajos Pusztai, an M.D. Anderson professor of breast medical oncology and lead investigator of one of the two studies. "We'll be able to select from a large number of seemingly appropriate chemotherapy choices the regimen most likely to cure an individual at diagnosis."
A predictive test for which chemotherapy will work in a given cancer patient would represent a major advance because it would eliminate the time-consuming, costly and potentially toxic trial-and-error that patients typically go through before finding effective treatment.
There are at least six different chemotherapy regimens that physicians commonly use to treat breast cancer, and what works for one patient often does not work for another. Treatment durations range from 12 weeks to 24 weeks, and drug prices range from $1,000 to $14,000, the longer and more expensive tending to be slightly more effective but also more toxic.
The test requires a needle biopsy of the cancer to be obtained along with the diagnostic biopsy. Genetic information about the cancer is extracted and tested on DNA chips, or microarrays, containing tens of thousands of human genes.
The chips show the gene profile of each cancer and help identify which are associated with "extreme" sensitivity to a drug regimen. Extreme sensitivity is the complete eradication of the cancer by pre-operative chemotherapy.
Pusztai used the diagnostic tool, also known as gene expression profiling, to determine which women with newly diagnosed, untreated breast cancer would experience such eradication by taking weekly paclitaxel followed by 5-fluoroucil, doxorubicin and cyclophosphamide (FAC) chemotherapy. Tested on 24 patients, the tool was 75 percent accurate.
At Baylor, Dr. Jenny Chang used the same kind of DNA microarray on docetaxel. Tested on 24 patients, it proved to be accurate 88 percent of the time.
"This confirms that breast cancers aren't all alike, and treatment can be tailored to individual tumors," said Chang, a professor of medicine. "As opposed to acquired resistance, which builds up with months of therapy, these results show that some women will be resistant to the drug from day one."
The DNA chip was developed by the California-based Affymetrix Company and is now available for laboratory research only.
Pusztai said his test using the DNA chip is probably two to three years from Food and Drug Administration approval for patient use.
Both Pusztai and Chang, who presented data about the studies at the American Society of Clinical Oncology annual meeting in Chicago, are working to improve their method's predictive accuracy. Pusztai said the ultimate goal will be to develop gene screens for all the common chemotherapy regimens.
"This kind of testing is the wave of the future," said Pusztai. "It's going to be the Microsoft of diagnostics."
Also at the ASCO conference, an M.D. Anderson researcher reported Monday that breast cancer in men is usually detected when the tumors are bigger, have spread and may be more aggressive, even though they're easier to feel than they are in women. The findings suggest that breast cancer in men may have important biological differences from the female disease, said Dr. Sharon Giordano, a professor of breast medical oncology who led the study.
Male breast cancer accounts for about 1 percent of all breast cancers, or about 1,600 new cases in the United States in 2002. Because it's so rare, little is known about whether it differs from breast cancer in women and how it should be treated.