BREAST CANCER DRUG AIMS AT GENES.

Byline: Lawrence K. Altman The New York Times

The first full-scale trials of an experimental drug that attacks a genetic defect in breast cancer cells show significant promise for women with advanced cancer, scientists reported Sunday in Los Angeles.

The drug, Herceptin, heightened the benefits of chemotherapy by shrinking tumors and slowing progression of a particular type of breast cancer, one that is responsible for about 30 percent of the 180,000 new cases of the disease in the United States each year, the scientists said at the annual meeting of the American Society of Clinical Oncology at the downtown Convention Center.

The improvement was seen among cases that had failed standard therapies.

Participants at the meeting greeted the reports with cautious optimism, and leaders said they were now planning to test the drug, which was developed by Genentech of South San Francisco, among patients with less advanced forms of the breast cancer and among the 20 percent of ovarian cancer cases involving the same genetic defect.

The University of California, Los Angeles, where much of the initial research on this form of breast cancer was conducted, issued a news release calling the development of the experimental treatment ``a significant medical breakthrough.''

Other experts agreed that it was a breakthrough. But they said their excitement primarily reflected a hope that with further research similar drugs could be developed for many types of tumors, opening a new frontier in cancer therapy. If such therapies do not prolong life, they may help people with advanced cancer work longer and enjoy life more. But the experts cautioned the public not to expect sudden success and stressed that it would take years and millions of dollars to complete such research.

Genentech said the Food and Drug Administration had granted Herceptin ``fast track'' status and that the agency would decide by Nov. 4 whether to approve it.

Until then, the drug is available only to participants in clinical trials and through a lottery under which Genentech is providing enough Herceptin for 100 women each quarter. The number may expand to 200 each quarter this summer.

Paul Laland, the chief spokesman for Genentech, said the company would be able to provide enough for about 50,000 women - the anticipated need - by the end of the year.

Herceptin is a protein known as a monoclonal antibody that was genetically engineered to bind to other specific proteins. The preliminary success with Herceptin and another monoclonal antibody for lymphoma was expected to revive interest in developing such compounds, a research avenue that scientists abandoned a decade ago because of lack of success.

Although Herceptin can cause heart damage when combined with certain other anti-cancer drugs, the scientists who conducted the studies said it was remarkably safe for an anti-cancer drug.

The studies reported Sunday were conducted in a number of medical centers throughout the world and involved women with a particularly aggressive form of cancer known as HER-2/neu. The cancer can progress rapidly to cause death sooner than other breast cancers.

At news conferences and presentations at the meeting in Los Angeles, attended by more than 19,000 cancer specialists, the scientists said they were impressed that weekly intravenous injections of Herceptin showed significant benefit among women who had cancers that had not responded well to standard treatment, including the most drastic, bone marrow transplants.

In one trial, women were treated with chemotherapy alone or Herceptin and chemotherapy. The addition of Herceptin led the cancers to completely disappear or shrink by half or more in 114 of 235 women, or 49 percent. This compared with 74 of 234, or 32 percent, in the group that received only chemotherapy.

After one year, 78 percent of those receiving Herceptin and chemotherapy were alive compared with 67 percent who received chemotherapy alone.

Because the full-scale studies began in 1995 and patients were still entering the studies last year, it was too soon to know how long the benefits would last, the scientists said.