Book Review: Tamoxifen: A Guide for Clinicians and Patients

July 1, 1997

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

It is unusual to find an entire book dedicated to one therapeutic agentbecause a balanced, comprehensive analysis generally requires a somewhatbroader perspective, particularly if it is targeted not only to the physicianstreating a particular disease but also to the patients experiencing it.Nevertheless, within its limited scope, this text certainly provides somevaluable material about the subject matter, 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 currentwidespread use of tamoxifen, provide an interesting window into the rigoroustriathlon a pharmaceutical agent must complete to be considered successful:(1) preclinical development and selection, (2) clinical development andregulatory approval, and (3) acceptance by the medical and scientific community.Accompanying this written account is an interesting collection of six photographiccollages of the editor at many stages of his career, together with thosecolleagues and friends that he felt made a substantive contribution tothe "successes of the past 28 years."

At the end of the book, a discussion of the drug development processin the United States, including definitions of phase I, II, and III trials,provides a formal summary, in generic fashion, to the many specific referencesabout tamoxifen development given throughout the text. This is furthersupplemented with a general description of the translational research process.

The first chapter of Tamoxifen: A Guide for Clinicians and Patientsprovides 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-approveduses of tamoxifen are provided, as are some relatively recent consensusgroup (St. Gallen) recommendations for the adjuvant treatment of breastcancer patients with lymph-node-negative and lymph-node-positive breastcancer. A review of the recurrence and survival meta-analysis data fromthe Early Breast Cancer Trialists Collaborative Group results is presentedin a series of 10 tables and several graphs. A discussion of the role ofendocrine therapy, including tamoxifen and oophorectomy, in premenopausalwomen with breast cancer is also provided. This chapter includes a discussionof 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 oftamoxifen on coronary artery disease, serum lipids, and osteoporosis. Thebeneficial effects of tamoxifen on the prevention of contralateral andipsilateral breast cancers are also summarized.

No consistent specific recommendation or guidelines are made with regardto the appropriate duration of tamoxifen therapy. One author, writing aboutthe treatment of postmenopausal patients, states that "the physicianmay have to individualize the decision by allowing those patients who standto benefit the most from tamoxifen therapy to extend the duration beyond5 years." This author does note that specific trials, such as theAdjuvant Tamoxifen-Longer Against Shorter (ATLAS) and the Adjuvant TamoxifenTreatment Offer More? (ATTOM), are underway to determine the appropriateduration of treatment. Another author, writing about the National SurgicalAdjuvant Breast Project (NSABP) protocol B-14, states that the resultsof this study clearly indicate that "tamoxifen should not be givenbeyond 5 years for women with node-negative disease."

Current knowledge about the degree of risk of endometrial cancer, alongwith the 1996 Committee Opinion of the American College of Obstetriciansand Gynecologists (AGOG) regarding screening for endometrial abnormalities,are nicely detailed. The conclusion that the benefits of tamoxifen greatlyoutweigh the risks of developing endometrial cancer are certainly justifiedand well supported, although the argument is somewhat redundant, at leastin 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 thisfrequently voiced concern is thoroughly addressed.

Conversely, the discussion about what to do after the completion oftamoxifen therapy is rather limited, particularly as development of tamoxifen-resistanttumors is such a frequently encountered problem. Only a few paragraphsare dedicated to the many other endocrine modulators, and no comprehensivereview of the literature or specific recommendations are provided.

A useful table listing some of the many organizations that provide resourcesto breast cancer patients and professionals is supplied. Also, a list ofkey issues regarding tamoxifen therapy and breast cancer in general isincluded, with the recommendation that the physician cover each of theseareas when discussing management with patients and families. This listis quite specific and practical. It is a good guide against which physicianscan assess the adequacy of their current communication practices. Assembledfrom the questions most frequently asked of information services providersat the National Alliance of Breast Cancer Organizations, the list makesit clear that more patients need to receive and understand this informationwhen interacting with their health-care providers.

This material is further supplemented by a roundtable discussion anda list of commonly asked questions about tamoxifen in two of the appendices.A synopsis of the efforts to develop pharmaceutical agents that will reliablyand safely prevent breast cancer is covered in the last chapter. Additionalappendices address the mechanism of action of tamoxifen and the importanceof BRCA1 mutations.

In summary, this is a valuable collection of information because itsynthesizes much of the literature focusing on which patient populationwill benefit most from tamoxifen therapy, adequately defines the risksand benefits of its use, provides useful general parameters for monitoringpatients receiving tamoxifen therapy, and clearly identifies specific areasabout this treatment modality for which patients frequently have inadequateinformation.

In general, the historical review of tamoxifen development and drugdevelopment will prove to be educational for many patients and cliniciansnot involved in this process. The information in many chapters is likelyto be difficult for some patients to understand because of its technicalnature. In addition, because the material is limited almost exclusivelyto tamoxifen, there are areas in which its practical value for both patientand clinician could have been substantively improved with an expanded discussionof the role of alternative therapies.