Some Implications of Steroid Hormones in Cancer: The Marie Curie Memorial Foundation Workshop Conference at the University of Surrey, Guildford (8th May, 1970)

By D. C. Williams and M. H. Briggs

Some Implications of Steroid Hormones in Cancer documents the proceedings of the Workshop Conference on Some Implications of Steroid Hormones in Cancer held at the University Of Surrey, Guildford on May 8, 1970. This book discusses steroids in relation to breast cancer in human females; studies on the uptake of estrogens by human breast tumors in vivo; and steroid metabolism in human breast cancer. The high-affinity estrogen receptors in hormone dependent tissues; some effects of steroid hormones on carcinogenesis in rats; and steroids and renal cell carcinoma are also elaborated. This text likewise covers the gut bacteria, steroids and cancer of the large bowel and in vitro screening test for hormonal and other forms of cytotoxic chemotherapy. This publication is beneficial to oncologists, medical practitioners, and students interested in the study of malignant diseases.

• Language: English
• Publisher: Elsevier Science
• Release date: Oct 22, 2013
• ISBN: 9781483193083

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Sussex

PREFACE

This volume consists of an account of a Workshop Meeting which was organised by the Marie Curie Memorial Foundation. It was held on the 8th May 1970 in the University of Surrey at Guildford. We should like to thank the Vice-Chancellor for his generous hospitality and Professor D. V. Parke for the excellent facilities, both scientific and social, which he so kindly arranged.

This was the second of an occasional series of meetings devoted to topics of current interest in the study of malignant disease. The object of these meetings is to bring together workers of different disciplines within the same general field of research. As with the first volume of the series we have tried to span the boundary between clinical and scientific disciplines over a fairly wide field of study.

At the present meeting we have attempted to widen the scope by considering some of the implications of steroid hormones in relation to cancer in general rather than restrict the discussion to a particular organ. The purpose of the meetings, however, remains unchanged; the promotion of free discussion and interchange of ideas between workers and especially the fostering of an ever closer understanding between clinicians and scientists.

It is a pleasure to thank Schering Chemicals Ltd., for their generous financial support without which this meeting would probably not have been possible.

Mrs. A. P. Lendon has once more earned our gratitude for her help with the organising of the meeting and Miss V. Barnes, B.Sc., for her transcription of the discussion sections and assembly of the manuscript.

Thanks are also due to our publishers, William Heinemann Medical Books Ltd. for the rapid publication of this volume.

D.C.W. and M.H.B.

September 1970

Participants

D.A. AUBREY, M.B., B.SC.(LOND.), F.R.C.S.,     The Royal Gwent Hospital, Newport

N. BISHUN, PH.D., M.I.BIOL., M.R.S.H.,     The Marie Curie Memorial Foundation Limpsfield Chart

M.H. BRIGGS, D.SC., PH.D., A.R.I.C.,     Schering Chemicals Ltd., Burgess Hill

JANET BROTHERTON, PH.D., A.R.I.C.,     The University of Surrey, Guildford

E. CAMERON, PH.D.,     Tenovus Institute for Cancer Research, Cardiff

J. CHAKRABORTY, PH.D.,     The University of Surrey, Guildford

I. CRAFT, M.B., B.S., F.R.C.S., M.R.C.S., L.R.C.P.,     Queen Mary’s Hospital, Roehampton

Prof. P. DAVIS, M.B., B.S., L.R.C.P., M.R.C.S.,     The University of Surrey, Guildford

Miss A. DAWSON, B.SC.,     The University of Cambridge, Cambridge

P.P. DENDY, PH.D.,     The University of Cambridge and Addenbrooke’s Hospital, Cambridge

D. DRASAR, PH.D.,     St. Mary’s Hospital, London

M. ELSTEIN, M.B., M.R.C.O.G.,     Southampton General Hospital, Southampton

E.N. GLEAVE, M.B., B.S., F.R.C.S.,     Welsh National School of Medicine, Cardiff

A. GLUCKSMANN, M.D., F.I.A.C.,     Strangeways Research Laboratory, Cambridge

K. GRIFFITHS, PH.D.,     Tenovus Institute for Cancer Research, Cardiff

P. HALL, PH.D.,     The Royal Infirmary, Glasgow

R.C. HALLOWES, M.B., B.S.,     Imperial Cancer Research Fund, London

M.J. HILL, M.B., B.CH.,     St. Mary’s Hospital, London

H. HILLMAN, M.B., B.S., M.R.C.S., L.R.C.P.,     The University of Surrey, Guildford

FRANCES JAMES, PH.D.,     St. Mary’s Hospital, London. St. Mary’s Hospital, London

Prof. V.H.T. JAMES, PH.D., D.S.C., F.R.I.C., M.R.C.Path.,     St. Mary’s Hospital, London. St. Mary’s Hospital, London

Prof. A.E. KELLIE, PH.D., F.R.I.C.,     Courtauld Institute, London

R. KING, M.SC., PH.D.,     Imperial Cancer Research Fund London

A.P. LENDON, Mrs., A.A.M.S.,     The Marie Curie Memorial Foundation, Limpsfield Chart

L. MARTIN, PH.D.,     Imperial Cancer Research Fund, London

Prof. D. PARKE, PH.D., F.R.I.C., F.R.S.M.,     The University of Surrey, Guildford

PEELING W.B., M.A., F.R.C.S,     The Royal Gwent Hospital, Newport

C.G. PIERREPOINT, PH.D., M.R.C.V.S.,     Tenovus Institute for Cancer Research, Cardiff

R.W. RAVEN, O.B.E., T.D., F.R.C.S.,     The Marie Curie Memorial Foundation, London

E. REID, PH.D., D.SC.,     The University of Surrey, Guildford

M. SMETHURST, B.SC., PH.D.,     The Marie Curie Memorial Foundation, Limpsfield Chart

J.A. SMITH, B.SC., M.SC.,     The Imperial Cancer Research Fund, London

MAXINE STAMFORD, M.B., CH.B., D.P.H.,     Schering Chemicals, Ltd., Burgess Hill

MISS D.A. TAYLOR, B.SC.,     Schering Chemicals, Ltd., Burgess Hill

D.C. WILLIAMS, PH.D., F.R.I.C.,     The Marie Curie Memorial Foundation, Limpsfield Chart

P.F. ZAGALSKY, PH.D.,     University of London, London

MORNING SESSION

Opening Address

D.V. PARKE, PROFESSOR

With the current widespread interest in biological regulation and enzyme induction, including on the one hand, those aspects that are concerned in carcinogenesis, and on the other, roles of steroid hormones as regulators, our conference today on the implications of steroid hormones in cancer would seem both apposite and opportune. It is obviously not without significance that the gonads and other sex organs—the ovaries and uterus, the breasts, the prostate and testes—which are the sites of much regulatory activity by steroid hormones, are also major sites of incidence of carcinogenesis, and many of the papers presented today will be dealing with these aspects of the problem.

The role of steroid hormones in regulating metabolic and cellular activity extends also to their effects, particularly with the adrenocorticoids, in regulating the immune response. With the current interests in the role of steroids as cytotoxic and immunosuppressive agents, and also in the immunological aspects of cancer, one wonders at the possible implications in this area, and no doubt this aspect of the problem will also be widely aired in our discussions.

The association of steroids with cancer is of course far from new, for back in the 1930’s there was a current belief that the steroid hormones secreted into the gastrointestinal tract might undergo chemical transformation to produce carcinogenic polycyclic hydrocarbons. This hypothesis was however very largely discounted by the 1950’s as it was by then realised that the necessary chemical reactions were not in the known repertoire of any mammalian enzymes. An appreciation of the enzymic versatility of the intestinal microflora has now restored this idea to the realms of possibility and we will be learning something of the latest development in this field also.

The great advantage to be derived from small intimate meetings, as we have with this workshop, is the propensity it imparts to speculative discussion. I trust that this will prove to be the case today, and with the experts that we have present, from many different scientific and clinical disciplines, the discussion, I am sure, will be scintillating as well as speculative.

Steroids in Relation to Breast Cancer in Human Females

RONALD W. RAVEN***,     Consulting Surgeon, the Royal Marsden Hospital and Institute of Cancer Research; Consulting Surgeon, Westminster Hospital; Chairman, Marie Curie Memorial Foundation

*Cole, P. and MacMahon, B. (1969). Lancet, ii, 604

**Wotiz, H. H., Shane, J. A., Vigersky, R. and Brecher, P. I. in Prognostic factors in breast cancer (1968), p. 368. Ed. by A. P. M. Forrest and P. B. Kunkler, E. and S. Livingstone, Edinburgh and London

Publisher Summary

This chapter discusses steroids in relation to breast cancer in human females. The cancer of the breast is a frequent, dangerous, and unpredictable disease that is closely related with steroid metabolism, exemplifying the intimate association that has always existed between oncology and endocrinology. This is a complex situation to clarify because one hormonal system is integrated with the functions of other endocrine organs so that a change occurring in one can involve the function of others, affecting many tissues and physiological processes in the whole organism. Both pregnancy and lactation interrupt the cyclic estrogen fluctuation, but lactation is not protective for breast cancer. There are many factors responsible for cancer, including differences in nutritional state and liver function, fertility, the use of various hormonal products, and the genetic factor. The latter is important as the offspring of females with breast cancer are in the high risk group for this disease. The ovary, adrenal, and hypophysis are all involved in the breast carcinoma problem, and other endocrine glands may be implicated like the thyroid. Steroid therapy and endocrine surgery have proved of great palliative value to many patients with disseminated breast carcinoma.

Cancer of the breast is a frequent, dangerous and unpredictable disease closely related with steroid metabolism, exemplifying the intimate association which has always existed between oncology and endocrinology since the inception of these disciplines. This is a complex situation to clarify because one hormonal system is integrated with the functions of other endocrine organs, so that a change occurring in one can involve the function of others, affecting many tissues and physiological processes in the whole organism. More recently oncology and endocrinology have been joined by another discipline, epidemiology, resulting already in posing important questions for solution by steroid chemistry research.

There are two main problems for laboratory and clinical steroid research to deal with. Firstly, to determine the role of steroids in the induction of neoplasia, and secondly, the effect of steroids on the maintenance and growth of cancer. The induction studies are chiefly made on rodents, largely mice, and their relevance to human breast cancer is debatable. The effects of steroids on established breast cancer have chiefly been worked out in humans, for the great benefit of patients and advancement of knowledge. The common animal tumours for laboratory research are usually hormone-resistant, but many human breast and prostate carcinomas are responsive, giving us valuable data. In this work, however, we are dealing with patients affected with metastatic disease causing deleterious immunological and chemical changes in the whole organism so that a complete picture incorporating early disease is not yet presented. But worthwhile treatment can now be given to patients with disseminated carcinoma of the breast and the clinician desires information about the actual steroid reactions he is creating. Such knowledge might lead to scientific control of a major variety of cancer. I feel, therefore, that this subject we consider today is important for clinicians and experimentalists. My particular contribution concerns steroids in relation to cancer of the breast in human females.

Epidemiological aspects

Steroid research will likely elucidate a number of questions now posed about breast carcinoma. In England and Wales more than 10,000 women died from breast cancer in 1968, as opposed to 76 men. Why are men infrequently affected and women so often, and why does female susceptibility increase uniformly with age? Marked changes in steroid chemistry are occurring at puberty, at the time of menstrual cessation, and with increasing age. How can we explain the protection against breast carcinoma afforded by the parous state, and increased when the first child is born with the mother under 20 years of age? Why should pregnancy decrease this cancer risk throughout life? Both pregnancy and lactation interrupt the cyclic oestrogen fluctuation, but lactation is not protective for breast cancer, demonstrated by women in India who suckle their children for periods up to two years, but develop breast cancer in large numbers. Unusual oestrogen metabolites in the urine have not been discovered, and specific excesses or decreased amounts of total oestrogens have not been demonstrated. There is considerable interest in the ratio of the impeded oestrogen-oestriol to the more strongly uterotropic oestrogens, oestradiol and oestrone. Wotiz and colleagues (1969) drew attention to a hypothesis whereby oestradiol may induce and promote neoplasia when not periodically interrupted by the action of oestrogens like oestriol, which is produced in high titres during