Am Fam Physician. 1998 Oct 15;58(6):1405-1406.
In patients with early breast cancer, all detectable cancer can be removed surgically from the breast or local lymph nodes. The threat of remaining micrometastases that might produce a clinically significant recurrence of the cancer several years after the original surgery has led to widespread use of tamoxifen. Although several studies indicate that tamoxifen improves survival and other outcome measures in some patients, the selection of appropriate patients and the duration of treatment remain unclear. The Early Breast Cancer Trialists' Collaborative Group used data from more than 36,000 women in 55 randomized trials to clarify the role of tamoxifen in the treatment of early breast cancer.
Information was sought on each woman participating in any randomized trial conducted since 1984, comparing treatment with tamoxifen with no treatment. The authors attempted to follow every woman until at least 1995. In the 55 trials, 36,689 women were followed for an average of 10 years. A total of 14,140 first recurrences of the cancer and 13,268 deaths were reported. The overall results showed significant reductions in mortality and recurrence in women who received tamoxifen. The proportional reductions in mortality for women who received tamoxifen for one, two and five years were 10, 15 and 22 percent, respectively. The corresponding rates of reduction in recurrence were 18, 25 and 42 percent. These benefits appeared substantially greater in women with estrogen-receptor (ER)–positive tumors. In the 18,000 women with ER–positive tumors, the proportional reductions in mortality at one, two and five years of tamoxifen therapy were 14, 18 and 28 percent, respectively. The reduction was greater in women with ER++ tumors (36 percent) than in those with ER+ tumors (23 percent). The reductions in rate of recurrence in ER–positive women with one, two and five years of tamoxifen therapy were 21, 28 and 50 percent, respectively. These benefits appeared to be largely irrespective of age, menopausal status, use of chemotherapy or daily dosage of tamoxifen.
The high prevalence of ER–positive tumors in younger women and the longer duration of follow-up contributed to the conclusion that tamoxifen benefited younger women as well as those older than 50 years of age or of post-menopausal status.
In the 8,000 women with ER–poor tumors, the proportional reduction in mortality was about 6 percent and the reduction in recurrence was about 10 percent. The authors conclude that the benefits of tamoxifen in patients with ER-poor tumors are unclear and require further research.
Endometrial cancer was the only cause of death that increased significantly in women treated with tamoxifen. The 32 cases recorded are almost double the incidence of endometrial cancer after approximately two years of tamoxifen therapy. However, the relative rarity of endometrial cancer compared to breast cancer means that the reduction in recurrent or contralateral breast cancers more than balances the increase in endometrial cancer. No significant increase was detected in the incidence of colorectal cancer. Tamoxifen has been shown to reduce blood concentrations of low-density lipoprotein cholesterol by about 20 percent. The theoretic decrease in cardiovascular disease related to reduction in low-density lipoprotein that is induced by tamoxifen could not be verified from the study data.
The authors conclude that although much remains to be elucidated, some years of tamoxifen therapy substantially improve the 10-year survival rate in women with ER–positive early breast cancer.
Early Breast Cancer Trialists' Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. May 16, 1998;351:1451–67.
Copyright © 1998 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact firstname.lastname@example.org for copyright questions and/or permission requests.
Want to use this article elsewhere? Get Permissions