Book Review

Selective Estrogen Receptor Modulators: A New Brand of Multitarget Drugs

N Engl J Med 2007; 356:429January 25, 2007

Article

Selective Estrogen Receptor Modulators: A New Brand of Multitarget Drugs
Edited by Antonio Cano Sanchez, Joaquim Calaf i Alsina, and José-Luis Dueñas-Díez. 357 pp., illustrated. Berlin, Springer, 2006. $169. ISBN: 978-3-540-24227-7

In the mid-1980s, it was discovered that the nonsteroidal antiestrogens tamoxifen and raloxifene (then known as keoxifene) can switch on (estrogenic action) or switch off (antiestrogenic action) responses at estrogen target sites around the body. This finding evoked a conceptual change in pharmacology that opened the door to investigations of the clinical potential of drugs that are now called selective estrogen receptor modulators (SERMs) for the prevention of breast cancer, osteoporosis, and other diseases in women.

Twenty years later, the veteran SERM tamoxifen is still used to treat and prevent breast cancer (antiestrogenic action), but raloxifene, the failed breast cancer drug, has been reinvented as a SERM and is used to treat and prevent osteoporosis (estrogenic action). Most important, raloxifene is particularly effective in preventing breast cancer in both normal-risk and high-risk postmenopausal women. The SERM concept works. As a result, medicine has changed, and physicians have new drugs that can prevent major diseases.

Sanchez and colleagues have assembled a timely addition to the clinician's library. Their book is an up-to-date synthesis of the basic mechanisms of action of estrogen and SERMs, with a comprehensive analysis of receptor-mediated and nonreceptor-mediated events in target tissue. The sections on new SERMs and the clinical endocrinology of SERMs are very useful and will remain so for some time. The choice of basic and clinical topics makes for interesting reading.

Clinicians will particularly like the second half of the book, in which the authors integrate the basic actions of SERMs and their clinical application. Because of its versatility and safety, raloxifene is the focus in discussion of the treatment and prevention of osteoporosis and the effect of the SERM on breast cancer, endometrial cancer, and coronary heart disease. Unfortunately, a recent study on the effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women torpedoes the notion that SERMs can prevent coronary heart disease (see Barrett-Connor et al. in the July 13, 2006, issue of the Journal). Nevertheless, perhaps in the future other SERMs will improve the prognosis for patients at high risk for death from coronary heart disease.

Some material of interest was omitted from the book. There is little mention of the historical importance of the discovery of SERMs or of their value in the evolution to drug development. I think it is often interesting to learn how laboratory studies actually change medicine. In addition, there is currently great excitement about the metabolism of tamoxifen — an old drug with a surprising secret. Tamoxifen is metabolically activated by the enzyme CYP2D6, so if patients also take certain selective serotonin reuptake inhibitors to prevent hot flashes, tamoxifen may not work optimally. This topic is of great clinical importance.

Overall, the book is well written and easy to read. SERMs have become important in general medical practice, so physicians would do well to better understand them as a new drug group.

V. Craig Jordan, Ph.D., D.Sc.
Fox Chase Cancer Center, Philadelphia, PA 19111
v.craig.jordan@fccc.edu