Book Review

Hormone Replacement Therapy and Cancer: The Current Status of Research and Practice

N Engl J Med 2002; 347:1898-1899December 5, 2002

Article

Hormone Replacement Therapy and Cancer: The Current Status of Research and Practice
(Controversial Issues in Climacteric Medicine Series.) Edited by Andrea R. Genazzani. 281 pp., illustrated. New York, Parthenon, 2002. $79.95. ISBN: 1-84214-079-5

A book that promises to summarize “the current status of research and practice” by its nature always falls short of the mark. There is no better example of such a book than this one on hormone-replacement therapy and cancer. Long-held notions about the benefits of hormone-replacement therapy were recently dispelled with the publication in the Journal of the American Medical Association of the first large randomized, placebo-controlled trial of conjugated equine estrogen plus medroxyprogesterone acetate in healthy women. Contrary to the results of previous case–control and cohort studies showing reduced rates of cardiovascular disease in women receiving hormone-replacement therapy, the Women's Health Initiative trial found an increased risk of heart attacks, strokes, and deep venous thrombosis and was stopped prematurely. This landmark trial will change the way in which, and the women for whom, such therapy is prescribed. Nevertheless, this book has value in that it is a collection of short, succinctly written chapters, mostly by European scientists and clinicians, that cover a wide variety of topics, including colon cancer. Colon cancer does not normally come to mind when one thinks about cancers related to hormone-replacement therapy, but previous studies and the recently reported trial may bring colon cancer and the possible protective effects of such therapy into sharper focus.

The book is organized into sections. The first section is a summary of basic-science topics, with individual chapters on oncogenes and tumor-suppressor genes, telomerase, metalloproteinases, and angiogenesis. These brief chapters remind me of articles that have appeared in the Journal and other publications summarizing basic research for clinicians and usually ending with consideration of how the research may become (or is) relevant to clinical practice. However, with the possible exception of the chapter on telomerase, there is little or no description of how these cellular processes relate to the actions of steroid hormones or to hormone-replacement therapy. One is left wondering why the editor chose these particular topics without providing a specific tie-in to the overall subject of the book.

The next section deals with breast cancer. These readable and informative chapters are brief summaries of the epidemiology, genetics, hormonal regulation, chemoprevention, and endocrine treatment of breast cancer. The chapter on endocrine and paracrine mechanisms in normal and malignant breast epithelium introduces the important concept of selective estrogen-enzyme modulators. In contrast to tamoxifen, a selective estrogen-receptor modulator that targets the estrogen receptor, selective estrogen-enzyme modulators target enzymes that control the production of estrogen within the breast tumor. Increasingly, estrogen production within the microenvironment of a tumor is recognized as fundamental to the growth, treatment, and prevention of breast cancer. The importance of selective estrogen-enzyme modulators was demonstrated by the results of randomized trials that established the superiority of aromatase inhibitors over tamoxifen in the treatment of women with advanced breast cancer, and recent results suggest that they may also be superior in treating early-stage breast cancer.

Topics related to endometrial cancer are covered next. I found these chapters particularly informative. The evidence of an increased risk of endometrial cancer in women receiving estrogen-only (“unopposed”) hormone-replacement therapy and a reduced risk of endometrial hyperplasia when a progestinal drug is added (“combination” hormone-replacement therapy) is nicely summarized. The authors of this chapter point out that the evidence that combination hormone-replacement therapy actually decreases the risk of endometrial cancer is “limited and contradictory.” Quite so, since these data were derived from population-based and case–control studies, not prospective trials.

Rates of colon cancer were significantly reduced in women who were randomly assigned to combination hormone-replacement therapy in the Women's Health Initiative trial. Why they were reduced is not immediately obvious, but hints are found in the section of the book devoted to colon cancer. Estrogen receptors are present in colonic epithelium, and epidemiologic studies show an inverse association between the use of hormone-replacement therapy and the incidence of colon cancer. In view of the results of the recent study, understanding the role of sex steroid hormones, hormone-replacement therapy, and the pathogenesis of colon cancer should be given high priority.

Conspicuously absent from this book is a summary of what is known about estrogens and Alzheimer's disease or neurocognitive function. Even in the last chapter, entitled “More Than Bones: Hormone Replacement Therapy for Mind and Body,” there is no mention of this topic.

Who will benefit from this book? Both primary care physicians and subspecialists who provide care to women may have something to gain from these brief overview chapters. With a field as difficult to grasp and rapidly changing as hormone-replacement therapy and cancer, these useful chapters serve to put the reader in the ballpark and identify the players. But if you are keeping track of the score, you will require more than this book provides.

Charles L. Shapiro, M.D.
Ohio State University Medical Center, Columbus, OH 43210
shapiro-1@medctr.osu.edu