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This book describes the principles underlying targeted hormonal treatments, assesses the actions of new and established agents, and illustrates the new applications of hormonal chemoprevention for breast cancer.
It has been recognized for many years that cancers originating in the breast and prostate gland are frequently 'endocrine-dependent. ' Traditional thera pies included surgical endocrine ablative procedures or pharmacologic hor mone administration, both designed to antagonize the stimulatory effects of sex steroid hormones. In the past decade, several new treatment strategies for these tumors have emerged from basic studies in reproductive biology and mechanisms of action of steroid hormones. In some instances, these new treatments have elimin ated or reduced the need for major surgical ablative procedures or for toxic hormone therapy. The clinical role for other new treatments has not yet been clearly defined, although exciting preliminary data from recent clinical trials are now available. Thus, an objective review of the current status of these new therapeutic approaches is of interest. In this volume we have attempted to provide an in-depth review of both basic and clinical research involving several new treatment strategies for breast and prostate cancer. The first three chapters summarize preclinical and clinical studies of the luteinizing hormone-releasing hormone analogues, which can be used effectively to induce 'medical castration. ' Chapters 4, 5, and 6 review the rationale and clinical use of the compounds known collec tively as the aromatase inhibitors, which can also be used to suppress sex steroid hormone levels. Antiestrogen mechanism of action and its clinical implications for the design of innovative treatment approaches is considered in chapters 7 and 8.
Breast cancer is one of the leading causes of cancer mortality in women worldwide, and the risk of disease recurrence continues despite improvements in screening and treatment. For patients with hormone receptor-positive breast cancer, some form of endocrine therapy is central to the management of their disease. Tamoxifen has long been the mainstay of endocrine therapy in this group of patients. However, there is mounting evidence showing that the aromatase inhibitors are able to reduce overall oestrogen levels and appear to be better tolerated over a long term than tamoxifen. New and emerging indications for the aromatase inhibitors are providing clinicans (and patients) with alternative treatment options with differing side effect profiles. Part of the Oxford Oncology Library, this pocketbook will summarise the latest evidence-based and practical information on the use of endrocrine therapies in the management of breast cancer (early stage, metastatic disease, and prevention of disease). With contributions from leading oncologists from the MD Anderson Cancer Center, the book covers the range of endocrine therapies currently available to clinicians including ovarian ablation, anti-estrogens, aromatase inhibitors, fulvestrant, progestins, androgens, and combination endocrine and chemotherapy. The book also includes useful chapters on the identification and optimal selection of patients for endocrine therapy as well as the role of endocrine treatments in the prevention of breast cancer. This book will serve as an invaluable reference for all health care professionals involved in the management of patients with breast cancer.
Starting in 1986, the European School of Oncology has expanded its activities in postgraduate teaching, which consisted mainly of traditional disease-orientated courses, by promoting new educational initiatives. One of these is the cloister seminars, short meetings intended for highly qualified oncologists and dealing with specific, controversial aspects of clinical practice and research. Another is the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on developments and treatment in specific fields of oncology. This series of ESO Monographs was designed with the specific purpose of disseminating the results of the most interesting of the seminars and study groups, and providing concise and updated reviews of the subjects discussed. It was decided to keep the layout very simple in order to keep costs to a minimum and make the monographs available in the shortest possible time, thus overcoming a common problem in medical literature: that of the material being outdated even before publication. Umberto Veronesi Chairman, Scientific Committee European School of Oncology Table of Contents How to Read this Monograph F.CAvALLI ......... . 1 Experimental Strategies for Studying the Development of Breast Cancer with Special Reference to Steroid Hormones, Growth Factors and Oncogenes R.J.B. KING . . . . . . . . . . . . . . . . . . . . . . . . .. . . . 5 . . .
Progress in basic research has made it necessary to redetermine the possibility of classic endocrine therapy for the treatment of patients with breast cancer. Exemplary, close cooperation between biochemis try and animal and clinical research led to a truly interdisciplinary and international exchange of ideas and experience at a symposium held in autumn 1978 in Heidelberg. We owe our thanks to ICI-Pharma for the kind support of this sym posIUm. The participation of Charles Huggins in the meeting as honorary chairman signified to all participants the meaning of this joint endeavour. It was the same Charles Huggins who through experimental work laid the foundation stone for endocrine ther apy of prostate and breast cancer, and who applied his findings clinically. Thousands of patients owe to him relief from their suffering. He contributed greatly to the attempt to find and stabilize the endocrine therapy for breast cancer, for which we thank him sincerely. We hope that the following contributions will similarly serve the well-being of our patients.
Breast and prostate cancers are both hormone-dependent, at least in some stages of their progression. Hormonal manipulation represents an important therapeutic approach. Although most of breast and prostate cancers initially respond to hormone therapy, most tumors reinitiate to growth. Finally, hormone-resistant and metastatic breast and prostate cancers may develop. Thus, the challenge is the dissection of mechanisms by which steroid receptor signaling pathways continue to influence cell growth and invasiveness. Compelling evidence indicates that steroid hormones elicit non-genomic responses in extra-nuclear compartment of target cells. In this cellular location, steroid-coupled receptors rapidly recruit signaling effectors or scaffold proteins and activate multiple pathways leading to proliferation, survival, migration and invasiveness. The immediate challenge is the dissection of key events regulating the steroid response of target tissues to prevent progression and improve treatment of breast and prostate cancers.
The European School of Oncology came into existence to respond to a need for informa tion, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was. considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Univer sities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of oncology.