WEDNESDAY, June 5, 2002 (HealthDayNews) -- Tamoxifen, the most widely taken breast cancer drug, has been linked to more than three dozen deaths from aggressive uterine tumors, prompting a more forceful package warning to women who would use it.
The Food and Drug Administration said that between 1978 and April 2001, at least 43 women in the United States and another 116 abroad developed uterine sarcomas after taking tamoxifen. Of those, 38 died of the cancers, many of which were advanced when diagnosed.
In recognition of the risk, tamoxifen packaging now bears a "black box" warning, the FDA's highest alert for prescription drugs. In addition to cautioning women about the risks of womb cancer, the box also warns them about tamoxifen's previously identified risks of lung clots and strokes.
However, officials and experts stressed that women with invasive breast cancer shouldn't stop taking tamoxifen. Rather, they said, the labeling change, which occurred last month, is aimed at women who are considering the drug as a way to prevent the disease or those with a localized tumor called ductus carcinoma in situ. In both groups, its value isn't certain.
"For women who have had invasive breast cancer, their risk of recurrence is much greater than a potential risk of tamoxifen, and the benefits of tamoxifen are well-established," said Dr. Susan Honig, an FDA official. Honig and two colleagues at the agency laid out the link between tamoxifen and uterine sarcoma, as well as the labeling changes, in a letter in tomorrow's issue of the New England Journal of Medicine.
By writing to the journal, the officials hoped to reach the widest possible group of doctors, since tamoxifen is now prescribed by not only cancer specialists but other physicians, too.
Tamoxifen, sold as Nolvadex by AstraZeneca Pharmaceuticals, is an anti-estrogen that blocks the growth-promoting effects of the hormone on breast tissue. But the drug also acts like estrogen on other tissues in the body, including the uterus, where it has been shown to boost the risk of a different form of uterine tumor called endometrial cancer.
Endometrial cancer typically occurs in the lining of the womb and triggers bouts of bleeding that prompt a visit to the doctor, so it's generally caught earlier than uterine sarcomas, which typically appear in deeper muscle and don't cause such obvious symptoms.
According to the FDA, the incidence of uterine sarcoma in women who've taken tamoxifen is between eight and 17 times higher than it is in the population as a whole. The disease is believed to affect between one and two women per 100,000 in this country.
The average age of the women who developed the tumors was 63 in the United States and 65 in Europe. They had been using the drug for an average of five years.
Honig said the FDA first learned of a possible connection in the summer of 2000, but that it took until only recently to investigate the cases.
Diane Wysowski, an FDA epidemiologist and co-author of the letter, said the agency and AstraZeneca agreed to the black box warning and a "dear doctor" notice the company sent last month alerting physicians to the new labeling.
Mary Lynn Carver, a spokeswoman at AstraZeneca's U.S. headquarters in Wilmington, Del., said the company has taken several steps in recent weeks to publicize the link between tamoxifen and uterine sarcoma. Along with issuing the "Dear Doctor" letter and announcing the label change at a meeting of cancer specialists in May, the company has also contacted leading cancer patient groups to inform them of the potential side effect.
While it's not clear how many women have taken tamoxifen, Carver said a half million in American alone have prescriptions for the drug at any given time.
Dr. D.L. Wickerham is associate chair of the National Surgical Adjuvant Breast and Bowel Project, a research effort sponsored by the National Cancer Institute that conducts clinical trials of treatments, including tamoxifen, for breast and colorectal cancer.
Wickerham, of Allegheny General Hospital in Pittsburgh, and his colleagues recently reported 12 cases of uterine sarcoma in 17,000 women who'd received tamoxifen for at least five years -- or less than 0.1 percent.
"This certainly should not be a factor in any woman taking tamoxifen to treat breast cancer," said Wickerham, who noted that the drug reduces the risk of death from the disease by about 25 percent.
However, he added, it could be more important to women considering the drug to prevent breast tumors, or those with in situ tumors, for whom the survival benefit of tamoxifen hasn't been proved.
In 1998, the NCI announced the results of a major tamoxifen study involving 13,000 women who were healthy but at risk of getting breast cancer. It said that those taking tamoxifen were 45 percent less likely to contract the disease than those taking a placebo. Soon after the announcement, the FDA approved the use of tamoxifen as a preventive.
What To Do
For more on tamoxifen, including the labeling change, try AstraZeneca. You can also check out the National Cancer Institute.
