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While there is growing excitement among researchers about the promise of personalized medicine, only a handful of gene-based tests are in wide use at present. “Why does the community oncologist in middle America generally not use such tests?” asks Todd R. Golub, an HHMI investigator who directs the cancer program at the Broad Institute of Harvard University and the Massachusetts Institute of Technology in Cambridge, Massachusetts. “That's simply because most of the early molecular genomic tests that are predictive of response to treatment have now gone into the black hole of validation—and have yet to emerge.”
Many of the initial reports of gene-expression profiles that could identify subtypes of cancer were based on only tens or perhaps hundreds of patients. “Before routinely implementing them in the clinic, we need to make sure they really hold up in many other patients and many other places,” Golub says. “This takes a lot of time and effort.”
A few tests have gone through more extensive validation, he says, and are available commercially to physicians. Among them are predictive tests for breast cancer recurrence, such as the Oncotype DX test in the United States and MammaPrint in Europe.
The Oncotype DX test focuses on 16 specific genes related to the molecular behavior of breast cancer cells in tumors removed from women with early breast cancers that are fueled by estrogen, giving each patient a score from 0 to 100. The higher the score, the greater the danger the cancer will return. Researchers at Genomic Health, Inc., of Redwood City, California, found these 16 genes to be least active in the tumors of patients who survived 10 years without a relapse. The very same genes were most active in the tumors of patients who had suffered bad outcomes.
At New York University School of Medicine, oncologist Ruth Oratz uses the test, and it has changed the way she treats some of her patients. Recently, a woman who looked like a good candidate to receive only hormonal treatments after her breast surgery and radiation—she was older, had a very small tumor, and no signs of cancer cells in the lymph nodes under her arm—was, according to the Oncotype DX, at very high risk of having a recurrence. “So she was given chemotherapy in addition to the hormonal treatment,” Oratz recalls. The test has made the pendulum swing the other way as well for some of Oratz's patients, leading them to forego aggressive chemotherapy when the test score was very low.
About 7,000 Oncotype tests were performed in 2005. Many insurers refused to reimburse the $3,460 cost because they were not convinced of the test's merits. The test received so much support from oncologists, however, that early this year Medicare decided to cover the cost for its beneficiaries. Several private insurers have begun covering it too.
Another widely accepted test called AlloMap, devised by XDx, Inc., in South San Francisco, recognizes the earliest steps of rejection in heart transplant patients by measuring the activity of 11 immunology-related genes. Thanks to this test, patients can now avoid many of the frequent and unpleasant heart biopsies they had to undergo to look for signs of rejection.
Photo: Noah Webb