Researchers called an early halt to two large, federally sponsored clinical studies of the drug Herceptin when it proved to be unusually effective at preventing cancer from recurring in women with early stage breast cancer.

The recurrence rate for women receiving Herceptin in addition to standard chemotherapy was half that of women in the trials who received only standard chemotherapy.

"This is a very dramatic jump," said Dr. Charles Geyer, director of breast oncology at Allegheny General Hospital and a leader of one of the Herceptin trials. "It's very exciting."

The drug will likely become part of the regular regimen for women whose cancer cells have an unusually large number of HER-2 proteins on their surfaces. An over-expression of HER-2 is found in between 20 percent and 30 percent of all breast cancers.

Herceptin, or trastuzumab, consists of antibodies that specifically attack those HER-2 proteins, slowing or stopping the growth of the cancer cells.

Combining Herceptin with certain chemotherapy drugs increases the risk of congestive heart failure, which could limit its use in some patients. But those heart effects may also be reversible and might be lessened by pairing Herceptin with different chemotherapy drugs.

The apparent success of Herceptin validates the strategy of cancer researchers to study the cancer cells themselves first, identify their vulnerabilities and then design therapies that target those vulnerabilities.

"This is really a case where we've now closed the loop on that," demonstrating that drugs developed by this strategy are indeed effective, Geyer said.

"This is a major advance for many thousands of women with breast cancer," agreed Dr. Andrew von Eschenbach, director of the National Cancer Institute, on Monday evening as he announced the early halt to the two trials.

"These results are one more example that we are at a major turning point in the use of targeted therapies to eliminate suffering and death from cancer."

The NCI sponsored both trials, which were run by the National Surgical Adjuvant Breast and Bowel Project, or NSABP, which is based in Pittsburgh, and the North Central Cancer Treatment Group, which is based at the Mayo Clinic in Minnesota. Genentech, which makes Herceptin, provided the drugs for both trials.

Cancer specialists had had high hopes for treating early stage tumors with Herceptin, which already is approved for treating advanced breast cancers that have spread to other organs.

"What surprised a lot of us," said Dr. Adam Brufsky, a medical oncologist at Magee-Womens Hospital, "was that the results came out so quickly."

The NSABP trial, for instance, began five years ago and was supposed to enroll 2,700 women. But that number was based on the assumption that Herceptin might reduce recurrence by 25 percent, Geyer noted. When it became apparent that the drug regimen was twice as effective as expected, the trial no longer needed so many patients to prove its point and was halted after enrolling about 2,100 women.

In treating advanced breast cancers, Herceptin was effective at extending the survival of patients, but it couldn't cure these advanced cases, Geyer said.

Of the combined 3,300 women enrolled in both studies, most had cancers that had spread no farther than adjacent lymph nodes -- a far more treatable stage. Preventing recurrence for seven years in these patients drops the risk for recurrence dramataically, although not eliminating it entirely, Geyer noted.

Breast cancer patients with "HER-2 positive" tumors are at heightened risk for cancer recurrence. In the NSABP trial, 67 percent of the women treated only with chemotherapy were alive after four years and most of those who died succumbed to recurrent cancer. By contrast, 75 percent of breast cancer patients undergoing chemotherapy overall survive four years.

The patients received a standard 12-week regimen of doxorubicin and cyclophosphamide, followed by 12 weeks of paclitaxel. The combination of Herceptin and doxorubicin is known to harm the heart, so Herceptin was added only for the second 12-week period and then continued for another 40 weeks after chemotherapy was complete.

Patients who undergo this chemotherapy regimen have a 1 percent risk of developing congestive heart failure; adding Herceptin boosted that risk to 3 percent or 4 percent.

Adding Herceptin to the regimen thus might not be appropriate for some patients already at risk for heart disease. But Brufsky, who participated in the NSABP trial, maintained that the heart failure associated with the therapy is reversible.

Also, the risk of heart failure might be reduced further by eliminating doxorubicin from the chemotherapy regimen, he added. That's being tested in another clinical trial of Herceptin, results of which are expected later this year.

Results from a European trial of Herceptin are expected to be released, along with additional details about the U.S. trials, at the American Society of Clinical Oncology meeting in Orlando, Fla., in mid-May. In the European trial, Herceptin was given only after chemotherapy was complete.