Tamoxifen reduces the chance of breast cancer in women with the BRCA2 mutation, but it doesn’t work for women with the BRCA1 mutation, according to a study reported in the Nov. 14 Journal of the American Medical Association (Vol. 286, No. 18: 2251-2256).

BRCA1 and BRCA2 are major known inherited gene mutations that lead to breast cancer. About 50% of women with either of these mutations will develop breast cancer, and ovarian cancer as well. But these mutations account for a small fraction — about 5% — of all breast cancers.

Mary-Claire King, PhD, and her colleagues looked at more than 13,000 women in a clinical trial of breast cancer prevention with tamoxifen. The trial, the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial, enrolled women who had a high risk of breast cancer, such as family history, previous breast cancer, or one of several other factors.

Half were given tamoxifen for five years and the other half received a placebo, an inactive substance that is used to compare the effects of a given treatment with no treatment. The women were followed for an average of nearly six years.

By the end of the study, 288 women had developed breast cancer. But, the women who received the tamoxifen had about half the number of cancers as those on placebo. These results, which were reported three years ago, have led many doctors to recommend tamoxifen for women at high risk of breast cancer.

The question asked by King was whether tamoxifen lowered the breast cancer rate in women who had either the BRCA1 or BRCA2 gene mutation. In the 288 women who developed breast cancer, they found 19 women with one of the two mutations.

Tamoxifen only seemed to help the women with the BRCA2 mutations. Their cancer rate was reduced by 62% compared to women who received a placebo. The women with the BRCA1 mutations treated with tamoxifen had the same cancer rate as women who were given a placebo.

Cancer specialists agree that breast cancers due to the BRCA1 mutation do not have estrogen receptors. These receptors are where tamoxifen does its damage to the cell. Without the estrogen receptor, breast cancer cells are resistant to tamoxifen. On the other hand, BRCA2 cancers often have these estrogen receptors.

The more that is known about the life-saving value of tamoxifen, the more easily women will be able to make decisions about selecting treatment. Currently many women with the BRCA mutations undergo prophylactic mastectomy, a treatment that has proven highly successful.

A study reported in the Nov. 7 issue of the Journal of the National Cancer Institute (Vol. 93, No. 21: 1633-1637) found that prophylactic mastectomy completely prevented breast cancer in women with either the BRCA1 or BRCA2 mutation.

Right now, these researchers say, "...evidence would favor tamoxifen for cancer-free women with BRCA2 mutation." But, they need to follow these patients for many years to see if this translates into a life-saving treatment. This information will be important in the future for those women thinking about prophylactic mastectomy.