THURSDAY, Sept. 12, 2002 (HealthDayNews) -- The drug tamoxifen can reduce the risk of breast cancer in women with higher odds of getting the disease, but a new study says it's not clear if the benefits of the drug outweigh its side effects.
Researchers in Britain, Australia and New Zealand found a 32 percent reduction in the risk of breast cancer in 3,578 women taking the hormone therapy. However, it turned up a doubling in potentially life-threatening blood clots, especially in women undergoing surgery or prolonged immobilization. And it found more than a doubling in the risk of death -- related to clots after surgery -- compared with 3,566 women receiving dummy treatment.
Dr. Jack Cuzick, the leader of the IBIS-I (International Breast Cancer Intervention) study, said in a statement: "Although when used as adjuvant therapy for breast cancer, tamoxifen can clearly reduce the risk of recurrence and death, at present the overall risk-to-benefit ratio in the preventive setting is still unclear. Further long-term follow-up to study breast-cancer incidence and mortality, other causes of death, and side effects in the current trials remains essential."
However, some American doctors disagree that tamoxifen was on a bubble. Dr. D. L. Wickerham, associate chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP), a major cancer research effort in the United States, says the results "confirm that tamoxifen is an effective drug." As for the clotting risk, Wickerham says that's "not news. Tamoxifen has been around since the 1960s," and doctors have long known about the elevated incidence of blood cots.
Wickerham, a breast cancer expert at Allegheny General Hospital in Pittsburgh, adds the risk is the same as that of estrogen in hormone replacement therapy for postmenopausal women: not negligible, but not so great to prevent them from taking it.
The researchers report their findings in this week's issue of The Lancet.
Tamoxifen is sold as Nolvadex by AstraZeneca. Many take it for the treatment of existing breast tumors, and a smaller fraction use it to prevent cancer from occurring.
The drug is a selective estrogen receptor modulator, or SERM. It binds to estrogen receptors and alters how cells react to the hormone. In the breast, it restrains estrogen activity, reducing the growth of cells. In the endometrium, it increases estrogen activity, pushing cell growth.
Three previous clinical trials of tamoxifen have shown it can cut the risk of breast cancer in high-risk women, such as those with a close relative with the disease, by about 50 percent over five years. That's in the ballpark of the latest study, which included more than 7,100 women between the ages of 35 and 70.
The researchers did see more uterine cancers in the women taking tamoxifen, 11 versus five, but the difference wasn't statistically significant and the tumors were easily removed by hysterectomy.
However, the clotting risk may be more troublesome, the scientists say. While some of the clots -- roughly half of which were in the leg veins -- occurred after leg surgery or a fracture, many others were spontaneous.
All of the excess deaths in the tamoxifen group occurred after surgery, the researchers say. As a result, "a wise precaution would be to discontinue" the drug before any operation and use anti-clotting therapy during the procedure. Tamoxifen should be resumed only when the woman is able to move around well.
Dr. Clifford Hudis, chief of the breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York City, says the latest research would be concerning had other studies not found no increased risk of death from tamoxifen. But "all the other studies show that you lower your breast cancer risk and the risk of death is neutral or better."
Still, Hudis says it's true that doctors need to refine their risk-benefit profile for the drug, especially in determining which women are the best candidates for therapy. Hudis considers tamoxifen most appropriate as a preventive in women at high risk of breast cancer. The IBIS study, he notes, included many women at moderately elevated risk of the disease.
What To Do
For more on tamoxifen and other ways of preventing breast cancer, visit the National Surgical Adjuvant Breast and Bowel Project or AstraZeneca.
