These conference proceedings reflect the resurgence of public awareness and research interest in the field of hormonal carcinogenesis, a phenomenon that is largely the result of the widespread use of therapeutic hormonal agents and the causal association of hormones and a variety of cancers, such as breast, prostatic, unterine and cervical. Significant attention is paid to the popular use of oestrogen therapies in women's health care.

It has been over a decade since the First International Symposium on Hormonal Carcinogenesis convened in 199 1. Since then, the field has rapidly expanded with considerable progress in both breast and prostate cancers; while ovarian and endometrial cancer have been hampered, in part, due to the absence of suitable hormone-mediated animal models. While knock-out, transgenic, and cell-culture systems have been extremely useful in identifying specific genelprotein alterations and the ensuing pathways affected, the precise molecular mechanisms whereby sex hormones elicit their oncogenic effects still remain elusive. Moreover, despite the considerable progress made in breast cancer research, the exact role of progestins in the presence or absence of estrogen in breast growth, differentiation, and malignant transformation is lacking. Elucidating the incipient molecular alterations in earlylpre-invasive lesions elicited by these hormones is a growing important focus of this field. The main purpose of these Symposia has been to address vital questions that impact our understanding of the causation, dependency, progression, resistance, and prevention of hormonally-associated cancers. We are indebted to the Scientific Advisory Board members who worked with us reviewing and offering suggestions to finalize the scientific program. We offer special thanks for the guidance and support of Dr. Gerald Mueller. His wisdom played an indispensable role in maintaining the excellence of these Symposia. We also acknowledge the numerous external reviewers that worked diligently to revise and improve the quality of the manuscripts. We are very grateful to Ms. Tandria Price.

Since our previous symposium in 1995, the pace of research in hormones and cancer has accelerated. Progress in our understanding of hormonal carcinogenic processes has been a direct result of the advances made in cell biology, endocrinology, and carcinogenesis at the molecular level. The newer fields of molecular genetics and cytogenetics already have and are expected to continue to playa major role in furthering our understanding of the cellular and molecular events in hormonal carcinogenesis. It has become increasingly clear that the risk of naturally occurring sex hormones in carcinogenic processes, both in human and in animal models, requires only minute quantities of hormones, at both the serum and tissue levels. Moreover, hormone target tissues for neoplastic transformation, perhaps with the exception of the liver, generally have relatively modest ability to metabolize sex hormones, such as the breast and prostate. Table 1 summarizes the serum, and in most cases, the tissue levels of sex hormones, both endogenously and exogenously ingested, which are associated with increased risk for endocrine-associated cancers such as breast, endometrium, and prostate, as well as the hormone levels of four experimental models that have been shown to elicit high tumor incidences. In contrast to the human, in which the hormone levels are cyclic, however, the latter require continuous hormone exposure at these relatively low levels.

Information gathered from cell-free systems, cell cultures, animal models, and human studies, together provide important insights to our understanding of hormonal cancer causation, development, and prevention; the primary objective of these Symposia. A special emphasis is placed on the two major endocrine-related cancers, that is, breast and prostate. The emerging fields of colon, lung, and pancreatic cancers in relation to hormones are examined.

For many years, Springer has been publishing an impressive series of textbooks of pharmacology which have set standards in medical science. Surprisingly, an extensive overview of the current state of the art in research on estrogens and anti estrogens was still lacking. The present two volumes on estrogens and anti estrogens provide a comprehensive review of a field of research in which remarkable progress has been made over the past few years. New insights into the mechanisms of steroid hormone action resulted in a tremendous number of pUblications from which new principles of preventive and therapeutic appli cations of estrogens and anti estrogens emerged. Although various electronic data bases provide easy access to this copious information, there was a clear necessity for a monograph-style textbook which assesses and summarizes current knowledge in this rapidly expanding field of research. It should be noted, however, that, due to this dynamic development, it is barely possible to comprehensively update every aspect of basic and clinical knowledge on estro gens and antiestrogens. Thus, the intention of the editors was to provide the reader with an overview of the "classic" and most recently explored areas of research and stimulate future interests in basic and applied endocrinology. Estrogens were among the first steroid hormones described in the scientific literature. Since they were first isolated, since the chemical, synthesic and pharmacological characterization of naturally occurring estrogens and, later on, of orally active derivatives, estrogen research has produced continu ously hallmark results in reproductive endocrinology worldwide.

In the past decade there has been a growing public interest and resurgence in research in the field of hormonal carcinogenesis. This is due to the widespread use of therapeutic hormonal agents worldwide and to the increasing awareness of the causal association of hormones, both endogenous and exogenously administered, and a variety of human cancers. These associations include estrogens in uterine, cervical, vaginal, liver, testicular, prostatic, and possible breast cancers; progesterone and progestational hormones in breast cancer; androgens and anabolic steroids in hepatic and prostatic cancers. Additionally, gonadotrophins playa role in the etiology of ovarian and testicular cancers and thyroid-stimulating hormones in thyroid cancers. Therefore, hormonal carcinogenesis encompasses the study of both natural and synthetic hormonal agents, including growth factors and other peptide and protein factors, which contribute substantially to the etiology of both human and animal neoplasms, benign or malignant. Hormones may be involved in all aspects of neoplastic transformation, including initiation, promotion, and progression, and the inhibition of these processes. There are a number of important issues in women's health that need to be addressed. More than 40 million U. S. women are menopausal, and these women have a life expectancy of over 30 years after the menopause. When these figures are multiplied worldwide, the numbers become staggering. After the menopause, estrogen replacement therapy (ERT) is the choice of most women in industrialized countries.

In the approach to the analysis of disease, including, of course, cancer, two major thrusts may be distinguished. These may be referred to, in shorthand, as agents and processes: the causative agents (chemical, microbial, physical, environmental, and psychosocial) and the organismic processes, initiated and furthered by the agents, culminating in observable pathology (at the macromolecular, cytological, histological, organ function, locomotor, and behavioral levels). The past 25 years, since the appearance of the first volume of the predecessor series (1) authored by the Editors of this present volume, have seen an impressive number of studies on chemicals (and other agents) as etiologic factors in the induction of cancer. The major emphasis has been on the discovery of many chemical carcinogens of widely different structures, their metabolism by various tissues and cells, and, in turn, their molecular-biochemical effects on the cells. This rapidly expanded body of information, as effectively covered in the predecessor volumes, is an excellent entree to the second half of the overall problem of chemical carcinogenesis, the processes. The active agents trigger a large array of molecular-biochemical alterations to which the target cells, target tissues, and target organisms respond in many select and common ways. This second major aspect of the induction of cancer by chemicals (and by other agents)- the sequence of cellular and tissue changes clearly relevant to cancer-remains the challenge for the future.

How to treat advanced prostatic cancer remains controversial, despite intense basic and clinical research investigating the pathogenesis and natural history of this unique cancer highly prevalent in elderly males. Nine experts were asked to meet and discuss the facts. This resulting monograph gives an overview of the available knowledge on all aspects of the subject. The objective evaluation and consensus opinion of the authors presented here set this book apart from other publications with conflicting viewpoints. For readers eager to obtain a comprehensive and balanced view of the thousands of clinical contributions and clear advice on the choices, this book is a must.

This volume presents a discussion of the biological effects produced following the metabolism of xenobiotic chemicals to chemically reactive metabolites, i.e., toxic and carcinogenic effects, which have been the basis of all five earlier volumes in this series. In particular, this volume devotes sections to structure-activity relationships, recent advances in the understanding of the chemistry of reactive metabolites, and the generation and activity of reactive oxygen species with special emphasis on nitric oxide. There are also segments on DNA damage by reactive metabolites and DNA repair, tissue specific responses to BRIs, and human health effects of BRIs. The papers that comprise this volume were submitted by world class scientists who were in attendance at The Symposium on Biological Reactive Intermediates VI at the Université René Descartes, July 16-20, 2000.