Breast Health

Tamoxifen Study Raises
Risk-Benefit Questions

But American physicians defend breast-cancer therapy

The drug tamoxifen, NOLVADEX® (tamoxifen citrate), can reduce the risk of breast cancer in women with higher odds of developing the disease, but a new study says it is not clear if the benefits of the drug outweigh its side effects. Picture of woman gardening

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 a placebo treatment.

Risk-Benefit Ratio in Preventive Setting Still Unclear

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."

Some American Physicians Disagree With Recent Findings

However, some American physicians 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 is "not news. Tamoxifen has been around since the 1960s," and physicians 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 a recent issue of The Lancet.

About Tamoxifen

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.

What Does Previous Research Say?

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 is 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 was not 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 is true that physicians 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.

Always consult your physician for more information.

October 2002
(October is National Breast Cancer Awareness Month)

Risk-Benefit Ratio in Preventive Setting Still Unclear

Some American Physicians Disagree With Recent Findings

About Tamoxifen

What Does Previous Research Say?

Cracking the Mystery of Breast Cancer

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Cracking the Mystery of Breast Cancer

Researchers map how changes to BRCA2 gene can lead to cancer

Mutations in a protein called BRCA2 can lead to breast and ovarian cancers, says a study in a recent issue of Science.

Memorial Sloan-Kettering Cancer Center researchers have uncovered the function of BRCA2 and the dangerous nature of mutations in the protein.

Previous research showed BRCA2 is a protective protein that prevents cancer development, but it was not clear this occurred. The researchers mapped out the structure of the BRCA2 protein and showed that it interacts directly with DNA to help repair genetic damage.

Left uncorrected, genetic damage can result in unstable chromosomes that can lead to cancer.

"If BRCA2 is altered or missing, it leads to a dangerous accumulation of genetic errors," says study senior author Nikola P. Pavletich, head of Sloan-Kettering's laboratory of structural biology of oncogenes and tumor.

"By studying the normal function of BRCA2, we can understand how changes in the protein contribute to the development of cancer," Pavletich says.

Always consult your physician for more information.