NEW BREAST CANCER HOPE; FDA PANEL BACKS DRUGS TO PREVENT, ATTACK DISEASE.

Byline: Gina Kolata and Lawrence M. Fisher The New York Times

An advisory committee to the Food and Drug Administration voted unanimously Wednesday to approve the use of a drug, tamoxifen, to reduce women's risk of developing breast cancer.

If the drug, which is already on the market, is approved for this purpose, it will be a milestone in efforts to prevent cancer, some experts said. Although it is intended only for women at high risk of breast cancer, it would nonetheless be the first drug that could prevent cancer in healthy people.

``As far as I know, this is the first drug approved for the prevention of cancer,'' said Dr. Leslie Ford, the associate director for early detection and community oncology at the cancer institute.

Wednesday evening, the advisory panel unanimously recommended approval for a new drug for women with advanced breast cancer.

The drug, Herceptin, is first in a wave of highly precise treatments that disable cancer cells through specific attacks on a cancer cell's weak points. Such drugs bypass normal cells and sidestep many of the distressing side effects of chemotherapy, such as nausea, weakness and hair loss.

Officials say Herceptin, made by Genentech, is intended for use by the estimated 30 percent of breast cancer patients who have a defective gene called HER2/neu that makes their cancer spread aggressively through the body.

Herceptin is considered the first major payoff of decades of basic scientific research into the inner working of cancer cells.

Now that scientists understand the genetic switches that can turn normal cells into disorderly, spreading monsters and understand how broken genes can send cells into spirals of cancerous growth, they can target those switches and replace those genes to choke off tumors and even prevent a cancer before it starts.

``It's a turning point in the war,'' said Dr. Dennis Slamon, director of the Revlon/UCLA Women's Cancer Research Program, the scientist who conducted much of the basic research that led to the drug's development. ``If we understand what's broken in a cancer cell we can develop more specific and better therapies. Now, we can do it again and again.''

While committee decisions still must receive formal approval from the Food and Drug Administration, votes by the FDA's advisory physicians are usually upheld. Final decisions are expected in November.

Tamoxifen is already on the market as a treatment to prevent recurrences of breast cancer in women who have had the disease. Since doctors can prescribe drugs for other than their approved uses, they could give tamoxifen to healthy women even without the FDA's approval. But approval of tamoxifen as a drug to reduce cancer risk would allow the company to advertise and market it widely for this purpose and would mean that health insurance companies would be more likely to pay for it for women who have never had cancer.

Supporters expressed delight that women would have a new avenue to prevent one of the diseases they dread the most. ``We're very pleased,'' said Susan Braun, the president and chief executive of the Susan G. Komen Foundation, an advocacy group for women with breast cancer.

But tamoxifen is not a panacea, experts warn, and the 11-member advisory panel said it did not yet have enough information to determine which women are at high enough risk of breast cancer to make the drug's hazards, including potentially fatal blood clots as well as cancer of the uterine lining, worth its benefits.

Critics say they fear that the drug will be overpromoted and that more women may be harmed than helped.

``The message we try to get across is that not everyone is at high enough risk to make this worthwhile,'' said Cindy Pearson, executive director of the National Women's Health Network. ``It isn't like putting iodine in your salt or chlorine in your drinking water. Women have already died taking this drug,'' she said, adding that it was still not clear that, in the long term, it would save lives.

Alan Milbauer, who is vice president for external affairs at Zeneca Pharmaceuticals, the Wilmington, Del., firm that makes tamoxifen, said the company plans to advertise the drug directly to women in 1999, after first educating general practitioners about its use. Milbauer said tamoxifen costs $80 to $100 a month.

Dr. Robert Justice, who is acting director of the division of oncology drug products at the FDA, said ``potentially tens of millions of women'' could be candidates for tamoxifen. He said Zeneca applied to market the drug for the prevention of breast cancer at the behest of the agency and the National Cancer Institute and called the advisory committee's decision to recommend that the drug be approved for this purpose ``courageous.''

Already demand for tamoxifen is starting to build. Dr. Barbara Weber, who directs the breast cancer program at the University of Pennsylvania, said that ``more and more women are calling me,'' asking about the drug and that other doctors have had the same experience.

Cancer experts had long hoped that tamoxifen might prevent breast cancer. Its biochemistry was promising, since it prevents the hormone estrogen from stimulating breast tissue. ``It's holding up across the board - in any setting where you get reduced exposure to estrogen, you get less breast cancer,'' Dr. Weber said.

For example, women who start menstruating late or who reach menopause early are less likely to develop breast cancer. But the notion of testing tamoxifen as a breast cancer preventive in healthy women was controversial because it would mean exposing women to the known risks of the drug to provide a possibly elusive benefit.

In April, shortly after the U.S. tamoxifen study ended, officials from the FDA, the cancer institute, and the U.S. tamoxifen study met and decided that the agency should consider allowing Zeneca to market tamoxifen as a breast cancer preventive, Justice of the FDA said.

If Herceptin is approved, it will be the first genetically engineered drug for the treatment of advanced breast cancer.

Herceptin has not yet been tested in earlier-stage breast cancer, but some specialists said they believed it could also prevent or delay the spread of the disease.

Although Herceptin potentially delays tumor progression in less than one-third of patients whose breast cancer has spread, or metastasized, cancer specialists said it represents an important step toward a new method of treatment.

Unlike chemotherapy, which kills fast multiplying cells, healthy as well as cancerous, Herceptin targets a specific genetic alteration linked to the cancer. Thus Herceptin has relatively few side effects.

Dr. Debu Trepathy, director of clinical trials at the breast care center of the University of California at San Francisco and a principal investigator of the drug, called the drug a breakthrough. ``There is no doubt in my mind that this is the beginning of a whole new wave of biological drugs that modulate the causes of cancer,'' he said.