New DNA test can reveal a tumor's ID

Profile of some cancers helps guide treatment

Joyce Hansen found herself going round and round in a circle of indecision that many cancer patients know all too well. Should she get chemotherapy or not? It promised only a slightly better prognosis for her breast cancer, and the list of potential side effects terrified her: nausea, vomiting, and exhaustion, possibly even permanent organ damage. On the other hand, how could she dare forgo something that might save her life?

Just a few years ago, Hansen would have had to make her decision based only on what doctors saw under a microscope and during surgery - pretty much the same way they had been diagnosing and treating cancer for decades. Instead, she and her doctor were able to turn to DNA, as well.

Breast cancer patients like Hansen are at the leading edge of what is one of the most eagerly awaited payoffs of human genome research: the ability to profile a tumor's genes and tailor treatment accordingly.

The reality is still in its infancy - the test Hansen took gave only a rough sense of what her benefit from chemo might have been - but genetic analysis of tumors is already being introduced for patients with lung cancer, and tests are under development for prostate cancer, kidney cancer, colon cancer, chronic leukemia, and more.

And "this is just a teaser of what's to come," said Dr. Eric P. Winer, director of the Breast Oncology Center at the Dana-Farber Cancer Institute.

As the research surges forward, scientists aim to be able to take the genetic fingerprint of any tumor, divine which genetic mutations drive it, and help clinicians choose the best weapons against it, said Eric Lander, director of the Broad Institute, the genomics powerhouse in Cambridge affiliated with MIT and Harvard University.

If there is a downside to these new tools, said Dr. Thomas Lynch, chief of Hematology and Oncology at Massachusetts General Hospital, it is "that we've got to have drugs to hit the targets." Researchers are quickly turning up relevant gene patterns, he said, but clinicians also need drugs to attack tumors with those patterns, and they can take years to develop.

"The biggest challenge in this field will be 'OK, so you've told me who's going to do well and who's not - what are you going to do about it?' " he said.

The tumor gene tests now entering the clinic are only the beginning, Lander emphasized: Behind them lie a "massive matrix of new genomic signatures now being generated by many researchers."

Seeking to make use of the research as it emerges, Dana-Farber opened a Center for Molecular Oncologic Pathology last summer, and Massachusetts General plans to open a pathology lab dedicated to broad-scale analysis of tumors at the molecular level.

Just last month, researchers from Brigham and Women's Hospital reported using a rapid new gene-analysis technique to pick up previously unsuspected mutations involved in mesothelioma, a form of lung cancer caused by asbestos.

The lead author of that paper, Dr. David Sugarbaker, said that now when he operates on a lung cancer patient, he sends a sample of tumor tissue out of the operating room to be reviewed by a pathologist.

"What I see in the future," he said, "is that I would take a piece of tumor out to the pathology room, we would quickly sequence it, and within a very short period of time, they would tell you, 'You've got this mutational profile and it responds best' " to a particular treatment. The genomic data might even save the patient from a major operation, he said.

Already in lung cancer, clinicians can test patients' tumors for mutations in a certain gene. About 13 percent of patients have it, and if they do they are treated with Erlotinib, a drug designed for that mutation, Lynch said.

"It can give them a better outcome with dramatically less side effects," he said.

Work is underway toward using genomic tests to help figure out why a given drug stops working, and why a patient relapses, he added.

In breast cancer, more than 46,000 patients nationwide have already had the same test Hansen did. Called Oncotype DX, the $3,500 test is recommended only for women with early invasive breast cancer that responds to the hormone estrogen. About 30 percent of patients for whom Oncotype DX is appropriate now opt for it, according to Genomic Health, the California company that makes it.

Hansen, who took the test in 2006, had to fight her insurance company to get it covered - even though, she pointed out, it probably cost about as much as one session of chemotherapy. Genomic Health says that insurer approval has gotten easier.

The test provides patients with a "recurrence score" between 0 and 100. Anything above 31 is considered high risk, meaning there is greater likelihood the tumor will recur and that the patient will benefit from chemotherapy. Hansen's score was not high, and the rest of her medical picture militated against chemotherapy.

The test "reassured me and helped me say, 'Yes, I will not have chemo,' " she said.

Hansen, a youthful 65-year-old former schoolteacher from Waltham, is determined not to second-guess her decision.

"Time, of course, will tell whether I made the right decision," Hansen said.

Source - The Boston Globe

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