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.

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.

Evaluates evidence for an increased risk of cancer in women using combined oral contraceptives, progestogen-only hormonal contraceptives, post-menopausal estrogen therapy, and post-menopausal estrogen-progestogen therapy. Although the carcinogenicity of these preparations has been extensively investigated, the book stresses the many complex methodological issues that must be considered when interpreting findings and weighing results. Evidence of an association between use of these preparations and positive effects on health, including a reduced risk of some cancers, is also critically assessed. The first and most extensive monograph evaluates evidence of an association between the use of combined oral contraceptives and cancer at nine sites. Concerning breast cancer, the evaluation concludes that, even if the association is causal, the excess risk for breast cancer associated with patterns of use that are typical today is very small. Studies of predominantly high-dose preparations found an increased risk of hepatocellular carcinoma in the absence of hepatitis viruses. Citing these findings, the evaluation concludes that there is sufficient evidence in humans for the carcinogenicity of combined oral contraceptives. The evaluation also found sufficient evidence for the carcinogenicity of some, but not all, combined preparations in animals. Combined oral contraceptives were classified as carcinogenic to humans. The evaluation also cites conclusive evidence that these agents have a protective effect against cancers of the ovary and endometrium. Progestogen-only contraceptives are evaluated in the second monograph, which considers the association with cancer at six sites. The evaluation found no evidence of an increased risk for breast cancer. Although the evaluation found sufficient evidence in animals for the carcinogenicity of medroxyprogesterone acetate, evidence for the carcinogenicity of progestogen-only contraceptives in humans was judged inadequate. Progestogen-only contraceptives were classified as possibly carcinogenic to humans. The third monograph, on post-menopausal estrogen therapy, considers evidence of an association with cancer at eight sites. Findings from a large number of epidemiological studies indicate a small increase in the risk of breast cancer in women who have used these preparations for five years or more. Studies consistently show an association between use of post-menopausal estrogen therapy and an increased risk for endometrial cancer. Data on the association with other cancers were either inconclusive or suggested no effect on risk. The evaluation concludes that post-menopausal estrogen therapy is carcinogenic to humans. The final monograph evaluates the association between the use of post-menopausal estrogen-progestogen therapy and cancer at four sites. The evaluation of limited data on breast cancer found an increased relative risk observed with long-term use. Data were judged insufficient to assess the effects of past use and of different progestogen compounds, doses, and treatment schedules. For endometrial cancer, the evaluation found an increase in risk relative to non-users when the progestogen was added to the cycle for 10 days or fewer. Post-menopausal estrogen-progestogen therapy was classified as possibly carcinogenic to humans. Concerning post-menopausal therapy in general, the book notes that evidence of carcinogenic risks must be placed in perspective of potential benefits. The prevention of osteoporotic fractures is cited as the best-established benefit. Evidence also suggests that estrogen prevents heart disease and may prevent memory loss and dementia.