NCI Comment on the Early Breast Cancer Trialists' Collaborative Group Meta-Analysis of Tamoxifen for Early Breast Cancer

National Cancer InstituteFor Response to InquiriesEMBARGOED FOR RELEASE, Thursday, May 14, 1998, 7:01 PM Eastern TimeNCI Press Office

In the May 16, 1998 issue of the journal Lancet, the international Early Breast Cancer Trialist's Collaborative Group (EBCTCG) published an overview of data from randomized trials of tamoxifen use in patients with early stage breast cancer.* Data from 37,000 women in 55 randomized trials beginning before 1990 were analyzed. Early stage breast cancer is cancer that is restricted to the breast and local lymph nodes (stage 1 and 2 disease).

The analysis published by EBCTCG showed that tamoxifen provides a clear benefit for women who had estrogen receptor-positive breast cancer; that is, their breast cancer cells are sensitive to the effects of the female hormone estrogen. Tamoxifen also provides benefit in women for whom estrogen-receptor testing was not done. When treated with tamoxifen for five years, these women together had almost 47 percent fewer recurrences and 26 percent fewer deaths than women who did not receive tamoxifen. Additionally, women taking tamoxifen had 47 percent fewer new breast cancers in the opposite breast than women who did not take the drug.

This analysis did not show that tamoxifen benefits women who had breast cancer that was estrogen receptor-negative (it is estimated that about one-third to one-half of all premenopausal breast cancer patients and one-quarter of all postmenopausal breast cancer patients have estrogen receptor- negative tumors). Whether or not tamoxifen should be used to treat women with estrogen-receptor negative tumors remains a research question.

The overview also confirms that treatment of estrogen receptor-positive breast tumors with five years of tamoxifen use provides premenopausal women with benefits equivalent to that received by postmenopausal women. The previous EBCTCG overview presented in 1992 did not conclusively demonstrate benefit for premenopausal women, but the additional data available for this overview now clearly show a strong benefit for tamoxifen in premenopausal women.

It is also noteworthy that the survival advantage for women treated with tamoxifen continues to increase up to at least 10 years, even though women in these trials were not treated with tamoxifen for more than five years. The National Cancer Institute does not recommend using tamoxifen in the treatment of breast cancer for longer than five years, outside of clinical trials.

Tamoxifen, while clearly beneficial for breast cancer, is not without hazards. Clinical trials have shown that tamoxifen can increase the risk of uterine (endometrial) cancers two to three times above that of the general population and doubles the chance of pulmonary embolism, a type of blood clot in the lungs that can be fatal. Both of these increased risk are similar to the increased risks seen in postmenopausal women taking estrogen replacement therapy. However, for women with estrogen receptor-positive breast cancer, this overview conclusively shows that the benefits of tamoxifen in preventing disease recurrence and death from breast cancer far outweigh the risks.

Often, women with early stage breast cancer do not have recurrence of their disease after initial surgical treatment. However, doctors cannot clearly define which women are most likely to have their disease return. It is therefore recommended that all women with early stage breast cancer consider adjuvant (additional) therapy. Physicians and patients should be aware of these long-term results from multiple clinical trials done in the United States and abroad. Adjuvant treatment with tamoxifen, with or without additional chemotherapy, should be carefully considered for all women with estrogen-receptor positive cancers.

*The study is titled "Tamoxifen for Early Breast Cancer: An Overview of the Randomized Trials." The authors are the Early Breast Cancer Trialists' Collaborative Group. Lancet, May 1998; 351: 1451-67.

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