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.

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.

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.

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.

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.

Cellular and Molecular Mechanisms of Hormonal Carcinogenesis ENVIRONMENTAL INFLUENCES Edited by James Huff, Ph.D., Jeff Boyd, Ph.D., and J. Carl Barrett, Ph.D. The influence of hormonal perturbations on carcinogenesis is attracting increased research attention today—a trend encouraged by the mounting number of both natural and synthetic hormone-mimetic agents found in certain drugs, industrial products or wastes, and elsewhere in the contemporary environment. Cellular and Molecular Mechanisms of Hormonal Carcinogenesis: Environmental Influences offers an authoritative, up-to-date overview of the role of environmental factors in the development of hormonally modulated cancers—as well as a comprehensive account of the latest research into the basic mechanisms of hormonal carcinogenesis in both human and animal models. The text opens with a review of the central issues relevant to environmental factors and hormonal carcinogenesis, including time trends, dietary effects, and chemically induced hormonal cancers. Subsequent sections examine molecular mechanisms and experimental and human mechanistic studies. Finally, the book closes with essays offering unique perspectives on this area, plus a discussion of the potential future of the field. Some of the specific topics covered in the text include: Dietary influences on tumors of hormonal tissues Modulating effects of hormones on carcinogenesis Transplacental hormonal carcinogenesis (diethylstilbestrol as an example) Estrogen as a carcinogen: genetics and molecular biology of human endometrial carcinoma Mechanisms of chemically induced follicular cell carcinogenesis of the thyroid gland Environmental causes of breast cancer: future research directions Featuring contributions from leading experimental and epidemiological researchers, Cellular and Molecular Mechanisms of Hormonal Carcinogenesis: Environmental Influences effectively summarizes the current status of this increasingly important area, and offers valuable data to guide ongoing investigations in the field. Biomedical and clinical researchers in oncology or endocrinology and cell/development biologists—particularly those interested in growth regulation or environmental toxicology—will find this work a stimulating and useful resource.

The series, Hormones in Health and Disease, was launched in 1993 to provide a scientific platform for investigators engaged in research on the biological actions of hormones and to anticipate relevance for their findings in clinical applications. The first volume of the series was dedicated to the discussion and understanding of molecular mechanisms by which steroid hormones influence target cells in normal and pathological conditions. With the diversity of information and the vast amount of literature on steroid hormone physiology, a more thorough treatment of Hormones and Cancer was identified as a timely topic. In this second volume in the series, Dr. Wayne V. Vedeckis has success fully undertaken the monumental task of editing the findings of the leading investigators in hormone and cancer research. Dr. Vedeckis brings to this project two decades of research experience in hormone action; he is actively engaged in elucidating hormone and cancer interrelations. It is a pleasure to welcome him to the series as an editor and congratulate him and all contribu tors in presenting this comprehensive treatise. The 20 chapters include discussions on contemporary topics relating control of cell division and signal transduction to the basic mechanisms of carcinogenesis by cloning patient genes, and recognizing the importance of steroid receptors in treatment protocols of various endocrine abnormalities.

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.