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Science Can't Predict Cancer's Return--Yet

Tests under development would identify risks with more certainty and eliminate needless treatments.


Though they've defeated the disease that could have taken their lives, cancer survivors are often haunted by the specter of a fatal recurrence.

The fears are especially keen for patients with slow-growing malignancies, such as those of the breast, because they never know if their cancer has been truly eradicated. They can suffer relapses five, 10, even 20 years later.

Although the risk of recurrence declines over time, it never disappears. "When it comes back, patients are devastated because they thought they had it licked," said Dr. Susan M. Love, a breast cancer surgeon at UCLA. And when cancer recurs, it's usually more aggressive and more difficult to treat.

Even using today's most precise prognostic tools, doctors are never sure which cancers will remain dormant and which ones will spread. That may change soon.

Screening techniques now under development may be able to identify the worst malignancies. Such tests, which examine the cancer cells' genetic makeup, would free people from this terrible uncertainty while sparing patients with indolent tumors from undergoing needless treatments that often have horrific side effects.

"These tests will revolutionize all cancer therapy," said Dr. Gabriel N. Hortobagyi, chairman of the breast medical oncology department at the University of Texas M.D. Anderson Cancer Center in Houston.

Knowing that about 25% to 33% of women with operable breast cancer will have a recurrence within five years of diagnosis, doctors currently must gather circumstantial evidence, such as the size, shape, location and microscopic appearance of cancer tumors, said Dr. Patricia A. Ganz, director of Cancer Prevention and Control Research at UCLA's Jonsson Cancer Center. Age can be a factor too: Premenopausal women tend to get more aggressive cancers than older women.

Genetic clues can also indicate which breast cancers are more deadly. The her-2 neu oncogene, for instance, which sparks virulent tumor growth, is present in about 25% to 30% of women with breast cancer. Also, the more advanced the cancer is (i.e., the higher its stage), the more likely it is to recur.

Women with tiny tumors confined to the milk ducts, called ductal carcinoma in situ, or DCIS, are often considered Stage 0 and are usually considered cured after treatment. While the highest risk of recurrence is in the first two years, even small Stage I cancers can reappear years later in a more lethal form.

Stage IV breast cancer has the poorest prognosis; it involves tumors that have spread to other parts of the body, such as bone, lung, liver and brain.

But even these factors don't provide a clear map of the future.

"Some women with the most favorable tumors will relapse, while some women with breast cancer that looks just awful will survive without a recurrence," said Hortobagyi. "Each case is different."

Part of the problem is that remnants of cancer may remain after a tumor has been cut out, triggering a relapse years later. Breast cancers also grow slowly. Consequently, tumors may sit in the breast for seven to eight years before they're large enough to be detected.

Doctors have no way of knowing if, during that time, malignant cells have already hitched rides in the lymphatic system or blood vessels and set up colonies in bones and vital organs such as the liver or lungs. When cancer does recur, "the cells may have been continuously growing, or they became dormant for a while and something wakes them up," Love said.

Because of this unknown, most women receive chemotherapy after their surgery to prevent the cancer from spreading, even though studies have shown that three-quarters of patients would do fine without this toxic therapy. "With chemotherapy we can reduce risks of recurrence by about a third," Ganz said.

Use of the drug tamoxifen, which blocks estrogen, a hormone that nurtures the growth of about half of all breast cancers, also cuts relapse risk by more than one-third. But again, it's unclear which women are being helped and which ones are being subjected to unnecessary treatments.

Such uncertainties could be resolved through the use of the new technology, called molecular profiling. In a study reported in January, scientists at Merck & Co. and the Netherlands Cancer Institute studied the genetic characteristics of 70 breast cancer patients, half of whom had a recurrence. They discovered that a different set of genetic patterns occurred for those with tumors that had spread throughout the body.

"Out of 25,000 genes, we were able to isolate several dozen genes that were clues to recurrence," said Dr. Stephen H. Friend, a study coauthor and a researcher at Merck in West Point, Pa.

It will take several years to refine this test, which probably won't be used on patients for four to five years. "But with this technology we hope to be able to forecast whose cancer will recur with a 90% degree of certainty," said Friend.

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