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 (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
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.