(The New York Times News Service) -- The drug tamoxifen, widely prescribed for women with breast cancer or at high risk for it, may cause a rare but aggressive cancer of the uterus, the Food and Drug Administration said Thursday.

The labeling of tamoxifen will be changed to add a "black box" warning about the newly identified risk for uterine sarcoma, the drug agency said. Black boxes are used to draw attention to problems that are serious and potentially life-threatening.

Letters advising doctors of the new warning were sent out last month, but the information was not posted on the FDA Web site until Thursday.

Doctors emphasized that the new warning was directed only at women who have not had breast cancer but are at high risk. The warning does not tell those women to avoid tamoxifen, but it does urge them to talk to their doctors about its benefits and risks.

The warning does not apply to women who have already had breast cancer and who take tamoxifen to prevent a recurrence. For those women, the drug agency said, the benefits far outweigh its risks.

Tamoxifen was already known to increase the risk of another, less dangerous type of uterine cancer, endometrial adenocarcinoma, which is usually detected at an early, curable stage. And women taking the drug were advised to have regular gynecological exams and to see a doctor immediately if they had symptoms like abnormal vaginal bleeding and abdominal pain and pressure. But the risk of the more dangerous type of cancer had not been recognized previously.

More than 4.5 million prescriptions for tamoxifen were written in the last year, according to IMS Health, a company that tracks the drug industry. Most users are women who have had breast cancer and who take tamoxifen to prevent recurrences. Other users, an unknown but small percentage, are women who have not had breast cancer but who are at high risk for it because of their personal or family medical histories. In that group, tamoxifen has been found to reduce the risk of breast cancer by 45 percent. Women usually take the drug for five years. It works by blocking the effects of estrogen, which can spur the growth of some breast tumors.

In women who have had breast cancer, the benefits of tamoxifen in preventing a recurrence are well established. Dr. Worta McCaskill-Stevens, a medical oncologist at the National Cancer Institute, said a 1998 analysis of 55 studies involving 37,000 women with breast cancer showed that those who took tamoxifen had a 46 percent reduction in cancer recurrence and a 27 percent reduction in the death rate after 15 years.

Dr. Larry Norton, a breast cancer specialist at the Memorial Sloan- Kettering Cancer Center in New York, said: "The impact of tamoxifen on saving lives of people with breast cancer is huge. It dwarfs any risk of dying of uterine sarcoma. There's no argument there."

Norton added that the evidence on uterine sarcoma had been accumulating for some time, and that the new warning would not come as a surprise to cancer specialists. He said studies were now under way to compare tamoxifen and another drug, raloxifene, which is now approved to prevent bone loss but is being tested to see if it can also prevent breast cancer without causing uterine cancer.

Besides women who have not had breast cancer but are at high risk, the warning is aimed at women who have had a very early form of breast cancer that is still confined to the milk ducts, called ductal carcinoma in situ, or DCIS.

In those two groups, unlike those who have had invasive breast cancer, it has not been proven that tamoxifen prolongs life, even though it does lower the risk of breast cancer.

Uterine sarcoma is very rare, and is estimated to occur in 0.17 women per 1,000 per year who take tamoxifen. In women not taking the drug, there are far fewer cases, only 0.01 to 0.02 cases per 1,000 women. Since 1978, when tamoxifen was first marketed in the United States, there have been 159 cases of uterine sarcoma reported in women taking the drug here and in other countries. About a quarter of the women have died from the uterine cancer.

Dr. Susan Honig, a medical reviewer in the division of oncology drug products at the Food and Drug Administration, said the drug agency began looking into the problem after it received reports about uterine sarcoma in women taking tamoxifen. She said the FDA worked with the drug company AstraZeneca, which sells tamoxifen under the name Nolvadex.

Fran Visco, president of the National Breast Cancer Coalition, a patient advocacy group, said: "You have to balance the risks and benefits very carefully in that situation. Are you trading off one life-threatening disease for another?"

Visco added that in healthy women at high risk, studies had shown that a five-year course of tamoxifen could reduce the incidence of breast cancer. But she went on: "All we know is it seems to result in a short term reduction in risk. We don't know if it truly prevents breast cancer or reduces mortality from breast cancer. We don't know the answers to what we think are the most important questions."

Carla Burigatto, a spokeswoman for AstraZeneca, said: " AstraZeneca believes there is a clear benefit of therapy for many women at high risk and with DCIS. We urge patients and physicians to have this dialog and decide what the best course of treatment is for each patient."

Copyright 2002 The New York Times News Service. All rights reserved.