Jonathan J. Li – författare

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.

Uniquely, Hormonal Carcinogeneis IV, integrates salient aspects of hormone-related cancers of interest to epidemiologists, basic researchers, and clinicians. The most recent advances in the major hormone-related cancers are presented by leaders of their specialty. The chapters in this volume deal with the causation, dependence, and resistance of endocrine-related cancer with particular emphasis on the most common neoplasms occuring in men and women world wide, such as breast, prostate, uterine and ovarian cancers.

Information gathered from cell-free systems, cell cultures, animal models, and human studies, together will (1) provide important insights to our understanding of hormonal cancer causation, development, and prevention; (2) be the primary objective of these Symposia.

Information gathered from cell-free systems, cell cultures, animal models, and human studies, together will (1) provide important insights to our understanding of hormonal cancer causation, development, and prevention; (2) be the primary objective of these Symposia.

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.

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.

For those of us who have labored in the field of hormonal carcinogenesis, it has been most gratifying to see its rapid growth and increasing relevance in recent years. Although many factors and forces have contributed to this phenomenon, a few appear particularly significant. Perhaps foremost is the realization that two of the most prevalent cancers which afflict women and men; that is, breast and prostate, have essential hormonal component(s) to their etiologies. This should not surprise us since the high frequency of these cancers in human populations has to date not been attributed to any exogenous physical, environmental, or dietary factor(s). A similar argument may be applied to other less prevalent but equally important cancers including ovarian, endometrial, testicular, cervico- vaginal, pituitary, thyroid, and sex hormone-associated hepatic neoplasms. The Office of Research on Women's Health and many women's interest groups have been instrumental in fostering research and public awareness on women's cancers. Similar concern is beginning to emerge for solely male cancers by other groups.To illustrate an example of the potential pervasive role of hormones in the human, particularly sex hormones, Figure I depicts the endogenous and known exogenous exposures to estrogens and progestins during a woman's lifetime, which may contribute to increased risk for hormonally-associated cancers . . = iii M. A. P. _ GI en 2 PoOlmenopauoal ~ EstrogDn ~ Proge. tln GI en J\ Ovulatory _ 2 Cyel. iii W DES EIP Menotr". 1 Ol,order.

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.