Williams / Briggs Some Implications of Steroid Hormones in Cancer

The Marie Curie Memorial Foundation Workshop Conference at the University of Surrey, Guildford (8th May, 1970)
1. Auflage 2013
ISBN: 978-1-4831-9308-3
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 148 Seiten

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.

Autoren/Hrsg.

Williams, D. C.

Briggs, M. H.

Leseproben

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). 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 pregnancy.

The marked differences in the incidence of breast cancer in ethnic groups of women have caused much interest, but we do not understand why the incidence is relatively low in Japanese women living in Japan and high in Great Britain. There are many factors to consider including differences in nutritional state and liver function, fertility, use of various hormonal products, and the genetic factor. The latter is important for the offspring of females with breast cancer are in the high risk group for this disease. It has been noted that in male relatives of breast cancer patients prostate cancer is more common than in the control population, (Macklin, 1954). The epidemiologist should now collect data about present usages of oestrogens, such as in foods, cosmetics, and the contraceptive pill. The short-term effects of the contraceptive pill are infertility, increase in the size of the breasts, abnormal endometrium and sometimes enlargement of the corpus uteri and excessive secretion from the cervix uteri. It is impossible to forecast the possible long-term effects of the pill steroids on the breast and other organs, but complacency about them is unwarranted.

There are also certain biochemical changes whose significance is unknown which include a rise in thyroxin-binding and cortisol-binding protein in the plasma, tissue fluid retention and an alteration in sulphabromophthalein liver clearance (see Hertz, 1969). We recognize that all known human carcinogens have a long latent period, in some cases up to 30 years, so that many years, perhaps 20, are likely to elapse before the full effects of the present-day use of steroids become manifest.

The importance of this prolonged, silent, latent period was shown by experimental observations of the interactions between oestrogens and progestogens on animal tissues resulting in pre-malignant metaplastic changes in the glands of the cervix uteri, endometrial carcinoma and ovarian tumours (see Lipschutz and Iglesias, 1961; Lipschutz and colleagues, 1962; Lipschutz and colleagues, 1967).

Endocrine organs and breast carcinoma

The ovary, adrenal and hypophysis are all involved in the breast carcinoma problem, and other endocrine glands may be implicated like the thyroid. I feel all the present evidence indicates that the ovary is of prime importance, but the way in which the tumour develops remains unknown. We can reflect upon some of the experiments associating the ovary. Mammary tumours in mice are reduced by oophorectomy; such tumours develop in castrated male mice after ovarian transplantation; and the production of these tumours by injecting natural and synthetic compounds. Carcinoma has been reported in the male breast following prolonged oestrogen administration to several patients with carcinoma of the prostate. In addition to ovarian secretions, those from the adrenal cortex and hypophysis also play a part. Following oophorectomy there is progressive hyperplasia of the adrenal cortex producing extragenital oestrogens.

Hypophysectomy in susceptible strains of mice markedly reduces the incidence of mammary tumours. This, in fact, is a complex endocrine problem and its solution is made even more difficult by the genetic factor and the milk agent transmitted by the mother which is involved in the development of the majority of mammary tumours in mice.

A study of naturally occurring breast cancers in animals has not given us much help. The disease is common in domestic animals dogs and cats, and can be just as malignant in the former as in the human female (see Innes, 1958).

Clinical observations in breast carcinoma

Steroid therapy and endocrine surgery have proved of great palliative value to many patients with disseminated breast carcinoma. Important clinical observations of these results now require scientific explanations, which may illuminate also other aspects of oncology. I reviewed the historical basis of this work elsewhere and called attention to the patients reported by Beatson...