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Tamoxifen Found Effective at Preventing Breast Cancer In Women with BRCA2 Gene Mutations, Not in Women with BRCA1 Mutations (dateline November 20, 2001)

Researchers know that some women carry abnormal forms of certain genes, called BRCA1 (breast cancer gene 1) and BRCA2 (breast cancer gene 2), that put them at higher than average risk for breast cancer. However, it has been unclear whether tamoxifen, a drug shown to reduce the risk of developing breast cancer in some high risk women, is effective in women with BRCA gene mutations. Now, a newly published study provides some answers. The study found that women who carry mutations of the BRCA2 gene can significantly reduce their risk of breast cancer by taking tamoxifen; however, tamoxifen does not appear to be particularly effective at preventing breast cancer in women with BRCA1 gene mutations. The researchers believe that the study can help physicians determine which high risk women are candidates for tamoxifen.

Some breast cancer cells depend on the hormone estrogen to grow and reproduce. Tamoxifen is an "anti-estrogen" drug that works by binding to estrogen-receptors on breast cancer cells so that estrogen cannot reach the cancer cells. Without estrogen, the cancer cells die. In addition to treating breast cancer, tamoxifen is also thought to prevent breast cancer by inhibiting the growth and survival of breast cancer cells with estrogen receptors.

In the study on tamoxifen published in the November 14, 2001 issue of the Journal of the American Medical Association, lead researcher Mary-Claire King, PhD and her colleagues attempted to determine whether tamoxifen is effective at preventing breast cancer in women who have tested positive for BRCA gene mutations. The study consisted of testing blood samples from 288 women who took part in the five-year National Surgical Breast and Bowel Project’s (NSABP) Breast Cancer Prevention Trial. All of the women in the study were age 35 or older and deemed at high risk for breast cancer.

Of the 288 women, 19 were determined to have BRCA gene mutations (8 with BRCA 1 mutations and 11 with BRCA2 mutations). The researchers found that women with BRCA2 gene mutations who took tamoxifen reduced their risk of developing breast cancer by 62%. However, the risk of breast cancer was not reduced with tamoxifen among women with BRCA1 gene mutations.

According to Dr. King and her colleagues, the findings are logical since 80% of breast cancer tumors among women with BRCA2 gene mutations contain estrogen receptors (which respond to tamoxifen) while nearly 80% of breast cancer tumors among women with BRCA1 gene mutations do not contain estrogen receptors (and thus do not respond to treatment with tamoxifen).

The researchers believe the results of their study will help some women who learn that they have BRCA gene mutations to make informed decisions about whether or not to take tamoxifen. This study, along with the NSABP trial and other data, also confirm that tamoxifen is an effective method of reducing breast cancer risk among certain women. However, tamoxifen is also associated with side effects, including hot flashes and vaginal dryness, and can slightly increase the risk of endometrial cancer (cancer of the uterine lining). Thus, tamoxifen is not appropriate for all women at high risk for breast cancer.

Women at high risk of breast cancer should talk to their physicians about ways to help prevent the disease. These options may include:

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