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Study: Tamoxifen's Benefits Are Selective

Blocks breast cancer linked to one gene mutation, but not another

TUESDAY, Nov. 13, 2001 (HealthDayNews) -- A new study says the drug tamoxifen can prevent breast tumors in women with one genetic mutation but is not as protective in women who have a sister mutation.

The study, appearing in the Nov. 14 issue of the Journal of the American Medical Association, shows that tamoxifen lowers the risk of breast cancer associated with BRCA2 gene errors by more than 60 percent, but doesn't seem to offer similar protection for women with BRCA1 mutations.

Study co-author Dr. Bernard Fisher, a cancer researcher at the University of Pittsburgh, says the findings don't mean all patients with BRCA1 mutations won't benefit from taking tamoxifen if they develop cancer. However, he says only about one in five BRCA1-related tumors will respond to the drug.

"If you have a BRCA2 mutation and you don't have a breast cancer, but you want to prevent it, then there is a good reason for taking tamoxifen," says Fisher, who is scientific director of the National Surgical Adjuvant Breast and Bowel Project.

The American Cancer Society says 192,000 American women will develop invasive breast cancer this year, and more than 40,000 will die from the disease. Inherited risk factors account for 5 percent to 10 percent of all breast cancers. Most result from mutations in the BRCA1 and BRCA2 genes, which provide instructions that help regulate cell growth. BRCA-related tumors are more common in Jewish women from Central and Eastern Europe.

While tamoxifen has been used for more than two decades to treat breast cancer, a landmark 1998 study found that the drug, sold as Nolvadex by AstraZeneca International, cut the likelihood these tumors would develop by nearly 50 percent. Later that year the U.S. Food and Drug Administration approved the drug, which blocks the action of estrogen on breast cells, for the prevention of breast tumors in women at high risk of the disease.

Women with either BRCA1 or BRCA2 mutations are 60 percent to 90 percent more likely than other women to develop breast cancer, experts say. But tumors caused by the two genes aren't identical.

Two years ago, researchers in Holland showed that about 80 percent of BRCA1 tumor cells are missing receptor molecules that make them sensitive to estrogen -- and therefore are considered "ER negative" -- whereas nearly 80 percent of BRCA2 tumors are "ER positive." For this reason, they suggested tamoxifen might not work as well at preventing cancer in BRCA1-positive women.

In the new study, Mary-Claire King of the University of Washington in Seattle led a team of scientists following 288 women with breast cancer who had been enrolled in a 1990s trial of tamoxifen's ability to prevent the disease. Of those, eight had BRCA1 mutations and 11 had BRCA2 errors.

Five patients in the BRCA1 group received tamoxifen while three were given a placebo. Three patients with BRCA2 mutations had received tamoxifen and eight had not. Overall, the researchers found the drug reduced the risk of breast cancer in women with BRCA2 mutations by 62 percent.

Fisher say although the number of women in the study with the two cancer mutations was small, "this fits the biology," so the outcome isn't likely to change as researchers expand their findings.

The study also looked only at women age 35 or older, so it's not clear whether starting tamoxifen earlier might have more general benefits. The drug does have several potentially serious side effects, including deep vein and lung clots and an increased risk of uterine cancer.

What To Do

If you have a family history of breast cancer, especially in close female relatives, get screened for breast cancer genes, Fisher says.

However, "just because you have a family history of breast cancer does not mean that you have BRCA1 or BRCA2," he says. "The more relatives you have with breast cancer, the more likely it is that you could have, but not that you do have, one of the BRCA mutations."

For more on breast cancer, visit the American Cancer Society.

To learn more about tamoxifen, try the Susan G. Komen Breast Cancer Foundation. For more on the genetics of breast cancer, try GeneticHealth or the University of Tennessee Medical Center.

SOURCES: Interviews with Bernard Fisher, M.D., distinguished service professor, University of Pittsburgh, and scientific director, National Surgical Adjuvant Breast and Bowel Project; American Cancer Society; November 1999 Journal of Clinical Oncology; Nov. 14, 2001 Journal of the American Medical Association
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