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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An understanding of the basic mechanisms of hormone action is becoming an important part of a clinician's training. With the advent of radioreceptor assays and their comparison with radioimmunoassays, we are becoming increasingly aware that the normal physiological function of a hormone is not necessarily dependent on "normal" levels of hormone being present in the plasma. Even if plasma levels are normal, if a particular target cell lacks the receptor for the particular hormone the target tissue will not respond to the hormone. It has been shown, for example, by many workers that steroid hormones act on their cells via a receptor located in the cytoplasm of the target cells (1-4). Since the presence or absence of such receptors are becoming increasingly important in terms of unexplained infertility, endometrial carcinoma and breast cancer, it is necessary that the practicing clinician be familiar with the concept of receptors and have some understanding of their mode of action. In this brief presentation, I will explain certain terminology and summarize the state of the art so that you can critically read the literature concerning new developments in the area of hormone action which is to become increasingly important in the next few years. I will discuss some of the aspects of the mechanism of peptide hormones such as LH and FSH but will devote most of my attention discussing the details of steroid hormone action since our knowledge in this area is much more complete. I will also explain the terms frequently discussed in the literature concerned with hormone-receptor interactions.
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PMID:Hormone-receptor interactions--basic mechanisms. 1 18

Cases included in a population-based case-control study of breast cancer in men were recruited from 10 geographic areas of the United States from 1983 to 1986. Controls, matched to cases on age and geographic area, were selected by random digit dialing for men under age 65 years and from Health Care Financing Administration files for older men. Results are based on responses from 227 cases and 300 controls to questions asked in a standardized personal interview. An increased risk of breast cancer was most strongly associated with undescended testes and was also related to orchiectomy, orchitis, testicular injury, late puberty, and infertility; and a decreasing trend in risk was observed with an increasing number of children. Relative risk estimates were also elevated in relation to a history of high blood cholesterol, rapid weight gain, benign breast conditions, and possibly obesity. These findings suggest that breast cancer in men develops in response to androgen deficiency associated with testicular dysfunction and under conditions associated with excess estrogen. Risk was also found to be elevated in men with a history of amphetamine use, diabetes, and cigar smoking and reduced in men with prior head trauma.
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PMID:Breast cancer in men: risk factors with hormonal implications. 135 Jul 8

The incidence of polycystic ovarian disease (PCOD) varies from 0.6 to 92%, depending on the parameters analysed, PCOD has been reported to appear in association with Cushing's Syndrome, adrenal hyperplasia, hypothyroidism, adrenal and ovarian tumours and some genetic abnormalities. The controversy regarding the pathophysiological mechanism underlying the disease still persists. Critical evaluation of old data, assessment of new findings concerning the possible role of insulin, growth factors and their binding proteins, and extrapolation of neuroendocrinological experiments enabled the construction of a concise hypothesis of the pathophysiology of PCOD. According to this hypothesis, PCOD is a multifactorial disease. The sequence of events finally leading to clinical manifestation of the disease (hyperandrogenism, abnormal luteinizing hormone pulsatility pattern and ovulation disturbances) may originate in different organs or be triggered by different mechanisms. It may stem from the adrenals, the hypothalamus or higher central nervous system centres, or from the ovary itself; it may originate from excess of fat tissue usually combined with hyperinsulinism; or may be the result of a net increase in active growth factors. Each of the above disturbances probably appears early in life, much before the clinical signs of the disease are evident. Predisposing factors such as gestational diabetes of the mother, childhood obesity, borderline adrenal hyperplasia and late menarche have to be looked for as early as possible in order to prevent the late consequences of the disease, such as increased risk of infertility, endometrial and breast cancer and cardiovascular disease.
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PMID:Pathophysiology of polycystic ovarian disease: new insights. 180 58

This updated literature review on heterosteroids and drug research has information on chemical structure, pharmacology, and effects. It first discusses the anti-inflammatory heterosteroids, such as mometasone furoate and cortivazol. It also covers heterosteroidal antimineralocorticoids and anabolic hetero derivatives. The review discusses at length the 19-norsteroid, mifepristone (RU-486), which exhibits antiprogestational activity and is being used for fertility control in women. It also has antiglucocorticoid activity and shows promise as a treatment of diseases characterized by muscle atrophy. In vitro studies indicate that mifepristone inhibits growth of breast cancer cell lines and of endometrial cancer cell lines. It has already exhibited growth inhibitory effects in some breast cancer patients. Discussions of mifepristone's pharmacokinetics and structural modifications of mifepristone follow. Danazol is an antigonadotropin and is used to treat endometriosis, benign breast disease, precocious puberty, hereditary angioneurotic edema, menorrhagia, some types of infertility, and gynecomastia. Danazol effects considerable changes in lipid metabolism. Other hormonal, antihormonal, and/or antifertility heterosteroids and/or aspects include androgen antagonists (e.g., cyproterone acetate), estrogen activity, antiestrogens, STS-557, and oximinosteroids. Heterosteroidal inhibitors of steroid hormone biosynthesis discussed are aromatase inhibitors, 5 alpha-reductase inhibitors, and 3 beta-hydroxysteroid dehydrogenase inhibitors (trilostane, epostane, and azastene). Heterosteroids affect the cardiovascular system, including the cardiac glycosides, antiarrhythmic agents, and antilipemic agents. Some heterosteroids affect central nervous system activity (e.g., RU-5135 causes convulsions in rodents). Pancuronium analogues and chandonium and analogues are neuromuscular blocking azasteroids. In addition to danazol and RU-486, several other antineoplastic heterosteroids exist (e.g., estramustine phosphate sodium, a prostate cancer drug).
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PMID:Heterosteroids and drug research. 184 48

Data from a case-control study that was conducted between 1980 and 1982 were analyzed to investigate the possible association between polycystic ovaries and the risk of breast cancer. The multicenter, population-based study included in-home interviews with 4,730 women with breast cancer and 4,688 control women aged 20-54 years. The age-adjusted odds ratio for breast cancer among women with a self-reported history of physician-diagnosed polycystic ovaries was 0.52 (95% confidence interval 0.32-0.87). The inverse association was not an artifact of infertility, age at first birth, or surgical menopause. Because women with this syndrome have abnormal levels of certain endogenous hormones, the observation of a low risk of breast cancer in this group may provide new insights into hormonal influences on breast cancer.
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PMID:Polycystic ovaries and the risk of breast cancer. 141 55

The present study investigated the problem of whether or not the intake of an Western-style diet will induce within the host a specified hormonal change that increases the risk for breast cancer (BC). The key observations obtained are as follows: 1) The risk for BC in Japan has been increasing for the last 20 years in parallel with the Westernization of dietary habits (increase of fat and animal protein in the diet). 2) A Japanese BC patient is distinguishable from a corresponding normal control by (a) an increase of waist/hip ratio (more specifically, an increase of abdominal fat) and (b) a decrease in the number of live births (relative infertility). Height, weight and height-adjusted weight all cannot distinguish the former from the latter. 3) The former is also distinguishable from the latter by dual steroidal disorders of ovarian dysfunction (progesterone depression) and hypercorticoidism, as revealed by a case control comparison of urinary steroid excretions. 4) The long-term maintenance of an experimental mouse on a fat-rich diet increased abdominal fat weight at an adult age, but not at a young age. 5) In the same experiment, the fat-rich diet produced a reduction of plasma progesterone at an early stage, and also produced dual changes of progesterone depression and corticosterone stimulation at a late stage of experiment. Plasma estradiol was little affected by an excess of dietary fat. 6) In an adult mouse, the weight of abdominal fat was increased by corticosterone treatment and was decreased by estradiol treatment. The suppressive effect of estradiol on abdominal fat weight was dose-dependent. In conclusion, our findings seem to suggest the possibility that a fat rich diet may produce dual steroidal disorders of ovarian dysfunction and hypercorticoidism which in turn will open the way to breast carcinogenesis by activating 2 proto-oncogens at the initiation and promotion steps.
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PMID:Nutrition and breast cancer risk in Japan. 206 29

The combined progestogen/estrogen oral contraceptive is the most common form of contraception in the US. They contain 1 of 5 synthetic progestogens (derived from 19-nortestosterone) and 1 of 2 estrogens. 3 new progestin compounds are in use in Europe and Asia. They are norgestimate, desogestrel, and gestodene. Estrogen seems to cause vascular complications. Progestin may cause atherosclerosis. Desogestrel and gestodene were studied for 6 months. They have little effect on glucose and lipid metabolism. Triphasal ethinyl estradiol/levonorgestrel and ethinyl estradiol/norethindrone (Ortho Novum 7/7/7) were compared in a 12-month prospective clinical trial. There seems to be no consensus of a pattern of increased breast cancer associated with oral contraceptive use. The UK National Case Control Study Group analyzed women younger than 36 years at the time breast cancer was diagnosed. 91% of their cohort had used pills. A significant trend was found when risk was analyzed with duration of taking pills. Women who had taken the pill for 4 years had no increased risk of breast cancer. However, there was an increased relative risk of 1.7 (P0.001) for women who took pills for more than 8 years. Among women using the pill for 8 years, the relative risk was 2.6 (p0.0001). AMong women using pills with 50 ug. of estrogen, the trend to increased risk was (P0.10). The 1988 National Survey of adolescent males showed that 60% of men never married were active sexually. Among 17- to 19-year-old-men who live in metropolitan areas, condom use has more than doubled, compared with 1979. In 1988, a "new" copper-containing IUD was approved for use in the US by the Food and Drug Administration, the Copper T 380 A. Pregnancy rates are less with this than with older devices. IUDs may cause pelvic inflammatory disease with resulting tubal infertility. However, the risk was overstated earlier. Women who have only 1 sexual partner in their lifetime had no significant risk of tubal infertility. "lost" IUDs continue to be a problem.
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PMID:Contraception. 210 26

The gonadotrophin releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); gonadorelin] agonist buserelin is a promising new agent in the treatment of a variety of disorders in gynaecology and andrology, paediatrics and oncology. While a single dose of buserelin stimulates the release of pituitary gonadotrophins, multiple doses produce reversible pituitary desensitisation, and this specific blockade of gonadotrophin support to the gonads provides the basis for the drug's efficacy in conditions dependent on sex hormone secretion. Thus, buserelin provides comparable efficacy to orchidectomy or high dose estrogens in the treatment of hormone-sensitive prostate cancer and exhibits a lower incidence of adverse effects. During the early phase of treatment it may be particularly useful in combination with antiandrogens. Buserelin also appears promising in hormone-sensitive premenopausal breast cancer. Extensive studies have proven the value of buserelin in endometriosis, where it produces a transient remission with gradual recurrence of the disease on cessation of treatment. Surgical intervention is necessary in severe disease after buserelin-induced involution of the lesions. In patients with uterine leiomyoma, preliminary data suggest that buserelin may be beneficial in rendering surgery more conservative by reducing fibroid size, although it appears unlikely to preclude surgical intervention. The use of buserelin to induce a state of reversible hypogonadotrophism before administration of exogenous gonadotrophins is a promising strategy in the treatment of infertility associated with polycystic ovary syndrome and other conditions of infertility with underlying ovarian dysfunction; such a strategy also clearly enhances the efficiency of in vitro fertilisation programmes. Initial studies suggest its potential usefulness as a female contraceptive when administered intermittently in conjunction with a progestogen. Buserelin represents a first-line treatment of central precocious puberty. In endometriosis the adverse effect profile of buserelin is generally favourable, with hypoestrogenic effects such as hot flushes and vaginal dryness, and decreased libido, predominating. There is no apparent detrimental effect on lipid metabolism. The potential for adverse hypoestrogenic effects on bone mineral content with long term administration remains to be clarified. Thus, the GnRH agonist buserelin represents an advance in the treatment of a variety of gynaecological and andrological as well as paediatric and oncological conditions, infertility and other sex-hormone dependent conditions, with a low incidence of adverse treatment effects.
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PMID:Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile. 210 79

This study was based on the data from 1214 women included in the controlled group within a hospital-based case-control study on the association between breast cancer and the use of oral contraceptives. This is a sample of middle-aged women. Women with a reason for referral, presumably associated with infertility, were excluded. Oral contraceptives are (apart from coitus interruptus) in 76% of the cases the method of contraception most frequently used, followed by the rhythm method and condoms. The use depends strongly on the age. Only 40% of the women, now 55-60 years of age, ever used oral contraceptives, whereas 91% of those now under 40 have been using them. Other connections can be seen with level of education, marital status, and reproduction and sex life. With the use of special preparations, there are differences between women of younger and older generations, partially based on the different times these preparations were introduced to the market. The exclusive use of sequential oral contraceptives decreases in the older cases.
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PMID:[Use of oral contraceptives in East Germany by middle-aged females]. 220 7

A population-based case-control study was conducted in Sweden and Norway to analyse possible associations between breast cancer occurring before the age of 45 and several different characteristics of the women's reproductive life. A total of 422 (89.2%) of all eligible patients, and 527 (80.6%) of all eligible controls were interviewed. In univariate analyses, different characteristics of child-bearing (parity, age at first birth, years between last birth and diagnosis, duration of breast-feeding, and number of induced and spontaneous abortions), measures of the fertile or ovulating period (age at menarche, years between menarche and first pregnancy, and estimates of the menstruation span) and symptoms of anovulatory cycles or infertility were all seemingly unrelated to, or at most weakly associated with breast cancer. Adjustment for possible confounding factors in multivariate analyses resulted in largely unaltered risk estimates with odds ratios close to unity and without any significant trends when the exposure variables were studied in categorised or in continuous form. We conclude that reproductive factors did not explain the occurrence of breast cancer before the age of 45 in this population.
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PMID:Absence of association between reproductive variables and the risk of breast cancer in young women in Sweden and Norway. 239 Apr 71


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