Medical Matters

Medical Matters

Gene profiling shows promise in diagnosis of cancer

Medicine & Science

April 14, 2003|By Judy Foreman | Judy Foreman,SPECIAL TO THE SUN

THERE'S A revolution brewing in the diagnosis of cancer that could change how doctors figure out which tumors are truly life-threatening -- and need chemotherapy -- and which are not.

In the Netherlands, the new tool, called gene expression profiling, is expected to be available for some women with breast cancer as soon as next month. In the United States, it could be several years before the technique is routinely available.

But if it lives up to its promise, thousands of patients a year with tumors deemed unlikely to spread might safely skip chemotherapy. At the other extreme, people with cancers deemed lethal might skip chemotherapy if it's unlikely to work, and go straight to experimental or alternative therapies.

With early-stage breast cancer, for instance, doctors overtreat because they can't tell which patients need chemotherapy and which don't. Dr. Eric Winer, director of the breast oncology center at the Dana-Farber Cancer Institute in Boston, estimates that in some situations, 100 women get chemotherapy for every 20 helped; in other cases, it's 100 to 1. With profiling -- also known as genetic fingerprinting, molecular signatures and molecular profiling -- the idea is to determine which genes are expressed, or turned on, in a given tumor.

Once genetically analyzed, tumors can be categorized and treatment chosen. Gene profiling will likely be used in addition to measures doctors now use, such as tumor size and whether the cancer has spread. It also is to be used to determine whether a tumor is likely to respond better to drug A or drug B.

Teams of researchers have studied gene profiling in different cancers and have seen little overlap in the genetic patterns.

Several years ago, scientists at Stanford University and elsewhere identified a set of 450 genes that can predict outcome in breast cancer. At Dana-Farber, researchers identified a set of 17 genes that seem to be harbingers of metastasis in cancers. And in the Netherlands, Rene Bernards and others identified a set of 70 genes that can predict which breast tumors will spread to other parts of the body, and which won't.

Researchers have used gene expression to predict outcome in cancers of the kidney, lung, prostate and blood. The idea that a tumor's potential to metastasize may be knowable while a tumor is small is both encouraging and distressing.

Historically, doctors believed tumors started off benign and mutated to acquire the ability to metastasize. "Our study shows that this notion, at least for breast cancer, is wrong," says Bernards. In other words, "small does not mean benign," he continues. "We have seen small tumors that are poor in outcome, and we have seen large tumors that have a good prognosis."

The idea that a tumor's destiny is immutable is disputed by Dr. Larry Norton, head of solid- tumor oncology at Memorial Sloan-Kettering Cancer Institute in New York. "It's a big stretch to say if a cancer is bad, you might as well give up," he says. "It may be that those tumors are the most curable with therapy."

Dr. Steven Goodman, a biostatistician and epidemiologist at Kimmel Cancer Center at the Johns Hopkins University, also is cautious. "There is absolutely zero evidence that by deferring chemotherapy based on these predictions you are better off," he says.

Despite concerns by some scientists that large prospective clinical trials should be conducted before gene expression profiling hits the clinic, the technique appears to be on the fast track. Bernards' company, Agendia Inc., to offer the test. Celera Diagnostics is doing a study correlating gene expression in breast tumors with progression of disease.

Judy Foreman is a lecturer on medicine at Harvard Medical School and an affiliated scholar at the Women's Studies Research Center at Brandeis University. Her column appears every other week. Past columns are available on

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