Book Review

Long-Term Tamoxifen Treatment for Breast Cancer

Tamoxifen: Molecular basis of use in cancer treatment and prevention

N Engl J Med 1995; 332:1655-1656June 15, 1995

Article

Long-Term Tamoxifen Treatment for Breast Cancer
Edited by V. Craig Jordan. 278 pp. Madison, University of Wisconsin Press, 1994. $40. ISBN: 0-299-14070-9

Tamoxifen: Molecular basis of use in cancer treatment and prevention
By Helen Wiseman. 209 pp. New York, John Wiley, 1994. $52.95. ISBN: 0-471-94316-9

Tamoxifen is an extraordinary drug. Even those mesmerized by rational drug design will marvel at its usefulness. Originally identified for one purpose for which it turned out to be totally ineffective in humans (as a “morning after” pill), tamoxifen ultimately proved useful as the most frequently prescribed anticancer therapy in the world. Its history is fascinating and revealing. It is an effective antifertility agent, but the beneficiaries of this effect are mice, not humans. Discovered in 1962 by Dr. Arthur Walpole of ICI Pharmaceuticals, the drug first known as ICI 46,474 is a remarkable anticancer agent whose full effects are still unknown and whose applications are still growing.

V. Craig Jordan, in his multiauthored work, beautifully combines the history and science of tamoxifen by recounting numerous scientific studies and personal observations. The histories of drug development, pharmacology, early animal studies on tumorigenesis, treatment of advanced disease in the early 1970s, incorporation into adjuvant therapies, and now, finally, investigation as a potential preventive agent are symphonically blended. Those who view tamoxifen simply as an “antiestrogen” will be humbled by the complexity of its interactions in women (estrogen levels do not fall, they increase) and come to realize why it remains important to study this drug incrementally and methodically. The overwhelming success of tamoxifen as a therapeutic agent in breast cancer has led to prevention trials in the United States and abroad. Appropriately, and perhaps in hopes of a final triumph for this medication, tamoxifen prevention trials are discussed in the last chapter, “The Prevention of Breast Cancer with Tamoxifen.” In fact, the authors point out that tamoxifen has already been shown to prevent breast cancer in women who have had a first cancer. They present the rationale for chemoprevention in healthy women whose estimated risk of breast cancer is high. Here, perhaps, there might have been more emphasis on possible severe side effects, such as uterine cancer. It remains the burden of the investigators to prove safety first, even before efficacy, in healthy women. The reader may come away from this chapter overly reassured about areas of concern raised in preceding chapters. This chapter does, however, issue a clear call for blinded randomized controlled trials of tamoxifen in this group of participants. This treatise on tamoxifen is a major and important work for everyone interested in women's health.

The work by Wiseman is complementary. It provides useful and interesting information about many other actions of tamoxifen, in addition to its clinical application in the treatment of breast and other cancers. The book is not meant to be a comprehensive review of clinical trials. Rather, it stimulates interest in the multiple mechanisms of action of the drug and, where necessary, cites relevant clinical observations. Discussions of tamoxifen as antioxidant and as a modulator of the immune response are highlights.

Remarkably, the combined cost of these books is under $100, and they are therefore of superior value. One comes away from both impressed by the successes of the past research on tamoxifen and by the multiplicity of directions that the research will take over the next 30 years.

John Erban, M.D.
New England Medical Center, Boston, MA 02111