It is unusual to find an entire book dedicated to one therapeutic agent because a balanced, comprehensive analysis generally requires a somewhat broader perspective, particularly if it is targeted not only to the physicians treating a particular disease but also to the patients experiencing it. Nevertheless, within its limited scope, this text certainly provides some valuable material about the subject matter, tamoxifen(Drug information on tamoxifen) (Nolvadex).
Of note, the historical recollections of the editor and principal author, V. Craig Jordan, PhD, DSc, regarding the process that led to the current widespread use of tamoxifen, provide an interesting window into the rigorous triathlon a pharmaceutical agent must complete to be considered successful: (1) preclinical development and selection, (2) clinical development and regulatory approval, and (3) acceptance by the medical and scientific community. Accompanying this written account is an interesting collection of six photographic collages of the editor at many stages of his career, together with those colleagues and friends that he felt made a substantive contribution to the "successes of the past 28 years."
At the end of the book, a discussion of the drug development process in the United States, including definitions of phase I, II, and III trials, provides a formal summary, in generic fashion, to the many specific references about tamoxifen development given throughout the text. This is further supplemented with a general description of the translational research process.
The first chapter of Tamoxifen: A Guide for Clinicians and Patients provides a succinct review of the known risk factors for breast cancer. Most of the remaining 13 chapters, after the thorough historical perspective, specifically address the issue of the use of tamoxifen. Current FDA-approved uses of tamoxifen are provided, as are some relatively recent consensus group (St. Gallen) recommendations for the adjuvant treatment of breast cancer patients with lymph-node-negative and lymph-node-positive breast cancer. A review of the recurrence and survival meta-analysis data from the Early Breast Cancer Trialists Collaborative Group results is presented in a series of 10 tables and several graphs. A discussion of the role of endocrine therapy, including tamoxifen and oophorectomy, in premenopausal women with breast cancer is also provided. This chapter includes a discussion of the side effects of tamoxifen in this age group.
A comprehensive analysis of other benefits of tamoxifen is also presented. Included are detailed discussions and summary tables of the effects of tamoxifen on coronary artery disease, serum lipids, and osteoporosis. The beneficial effects of tamoxifen on the prevention of contralateral and ipsilateral breast cancers are also summarized.
No consistent specific recommendation or guidelines are made with regard to the appropriate duration of tamoxifen therapy. One author, writing about the treatment of postmenopausal patients, states that "the physician may have to individualize the decision by allowing those patients who stand to benefit the most from tamoxifen therapy to extend the duration beyond 5 years." This author does note that specific trials, such as the Adjuvant Tamoxifen-Longer Against Shorter (ATLAS) and the Adjuvant Tamoxifen Treatment Offer More? (ATTOM), are underway to determine the appropriate duration of treatment. Another author, writing about the National Surgical Adjuvant Breast Project (NSABP) protocol B-14, states that the results of this study clearly indicate that "tamoxifen should not be given beyond 5 years for women with node-negative disease."
Current knowledge about the degree of risk of endometrial cancer, along with the 1996 Committee Opinion of the American College of Obstetricians and Gynecologists (AGOG) regarding screening for endometrial abnormalities, are nicely detailed. The conclusion that the benefits of tamoxifen greatly outweigh the risks of developing endometrial cancer are certainly justified and well supported, although the argument is somewhat redundant, at least in this reviewer's opinion, with two full chapters devoted to this issue. Perhaps this is a result of the author's desire to be certain that this frequently voiced concern is thoroughly addressed.
Conversely, the discussion about what to do after the completion of tamoxifen therapy is rather limited, particularly as development of tamoxifen-resistant tumors is such a frequently encountered problem. Only a few paragraphs are dedicated to the many other endocrine modulators, and no comprehensive review of the literature or specific recommendations are provided.
A useful table listing some of the many organizations that provide resources to breast cancer patients and professionals is supplied. Also, a list of key issues regarding tamoxifen therapy and breast cancer in general is included, with the recommendation that the physician cover each of these areas when discussing management with patients and families. This list is quite specific and practical. It is a good guide against which physicians can assess the adequacy of their current communication practices. Assembled from the questions most frequently asked of information services providers at the National Alliance of Breast Cancer Organizations, the list makes it clear that more patients need to receive and understand this information when interacting with their health-care providers.
This material is further supplemented by a roundtable discussion and a list of commonly asked questions about tamoxifen in two of the appendices. A synopsis of the efforts to develop pharmaceutical agents that will reliably and safely prevent breast cancer is covered in the last chapter. Additional appendices address the mechanism of action of tamoxifen and the importance of BRCA1 mutations.
In summary, this is a valuable collection of information because it synthesizes much of the literature focusing on which patient population will benefit most from tamoxifen therapy, adequately defines the risks and benefits of its use, provides useful general parameters for monitoring patients receiving tamoxifen therapy, and clearly identifies specific areas about this treatment modality for which patients frequently have inadequate information.
In general, the historical review of tamoxifen development and drug development will prove to be educational for many patients and clinicians not involved in this process. The information in many chapters is likely to be difficult for some patients to understand because of its technical nature. In addition, because the material is limited almost exclusively to tamoxifen, there are areas in which its practical value for both patient and clinician could have been substantively improved with an expanded discussion of the role of alternative therapies.