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.

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.

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.

Protooncogenes and Growth Factors in Steroid Hormone Induced Growth and Differentiation reviews current information regarding the complex nature of hormone-induced cell growth and differentiation. The contributors examine the emerging consensus that protooncogenes and growth factors mediate perhaps the most crucial steps leading to cell growth and differentiation. The primary objective of this book is to unite the status of current research related to protooncogenes and growth factors from diverse physiological systems to help readers gain a comprehensive understanding of the subject. Leading researchers have contributed outstanding chapters pertaining to steroid hormone-regulated cell growth and differentiation in normal and/or neoplastic tissues. This book will appeal to basic science researchers, clinicians, industrial researchers, and graduate students.

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.

Oral contraceptives for family planning worldwide have revolutionized the reproductive lives of millions of women since their introduction in the 1960s. Later on, a variety of side-effects including cardiovascular diseases was recognized. In response to these concerns, new generations of combined oral contraceptives were developed that featured lower dose of estrogen and newer, more potent progestogens. The effectiveness and ease of use of combined hormonal contraceptives suggest that they will continue to be used to a significant extent in the future. This ninety-first volume of IARC Monograp.

Recent Progress in Hormone Research, Volume 33 covers the Proceedings of the 1976 Laurentian Hormone Conference. The book discusses the expanding significance of hypothalamic peptides; the LATS in Graves' disease; and the ontogenesis of hypothalamic-pituitary-thyroid function and metabolism in human, sheep, and rat. The text also describes the antimullerian hormone; the evolution of gonadotropin structure and function; and the biosynthesis of parathyroid hormone. The carbon-13 nuclear magnetic resonance investigations of hormone structure and function; the regulation of vasopressin function in health and disease; and some considerations of the role of the antidiuretic hormone in water homeostasis are also considered. The book further tackles the clinical significance of circulating proinsulin and C-peptide; glucagon and the A cells; and a newly recognized pancreatic polypeptide. The text then encompasses the steroid hormone actions in tissue culture cells and cell hybrids and their relation to human malignancies; and the role of hormones on digestive and urinary tract carcinogenesis. Endocrinologists, neuroendocrinologists, and oncologists will find the book invaluable.

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.

Androgens are critical regulators of prostate differentiation and function, as well as prostate cancer growth and survival. Therefore, androgen ablation is the preferred systemic treatment for disseminated prostate cancer. Androgen action is exerted in target tissues via binding the androgen receptor (AR), a nuclear receptor transcription factor. Historically, the gene expression program mediated by the AR has been poorly understood. However, recent gene expression profiling and more traditional single-gene characterization studies have revealed many androgen-regulated genes that are important mediators of androgen action in both normal and malignant prostate tissue. This book will focus on the androgen-regulated gene expression program, and examine how recently identified androgen-regulated genes are likely to contribute to the development and progression of prostate cancer. Recent studies that have attempted to unravel how these genes are deregulated in androgen depletion independent prostate cancer will be included