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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A reappraisal of endometrial cancer over the past decade reveals: 1) new concepts in its pathologic nature; 2) increase in incidence; 3) acceptance of the theory of hormonal relation; and 4) acceptance of individualization of treatment. Although endometrial carcinoma is still thought of as a predominantly well-differentiated adenocarcinoma, an increase in more virulent tumors has been seen in recent years. These include: adenosquamous carcinoma; adenoacanthoma; mesodermal sarcomas; and adenometous hyperplasia. Women at high risk for these tumors include those suffering from obesity, infertility, failure of ovulation, dysfunctional uterine bleeding, and those on long-term estrogen therapy. These women can be recognized and monitored by means of endometrial biopsy of the aspiration-curettage type. Adenomatous hyperplasia, the precursor of cancer, requires treatment with progestin or hysterectomy according to patient's age and reproductive status. Estrogens should be used only when indications are clear and in the smallest possible dose for the shortest period of time until the therapeutic goal is achieved. Aggressiveness of treatment should correspond to virulence of tumor. Dilatation and curettage under anesthesia should be used for clinical staging of endometrial cancer. Other means of treating endometrial cancers' include: total hysterectomy; bilateral salpingo-oophorectomy; iliac-aortic lymphadenectomy; pelvic irradiation; radical hysterectomy; chemotherapy, and a drug regimen (including cyclophosphamide, doxorubicin, fluorouracil, megestrol acetate).
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PMID:Current concepts in cancer: The changing nature of endometrial cancer. 735 80

This paper summarizes the available data on the efficacy of endocrine and cytotoxic therapy for breast cancer in pre- and postmenopausal women. Various studies which were conducted suggested that regardless of hormone receptor status, premenopausal women should receive combined endocrine and cytotoxic therapy. However, it is now believed that future trials should take into account hormone receport status. For ER+ tumors, the standard initial treatment should be ovariectomy and later tamoxifen and chemotherapy could be added. A table, included in this brief review, summarizes treatment strategy for premenopausal women. If ER status is unknown treatment should include ovariectomy and combination chemotherapy; if ER+, ovariectomy along with tamoxifen and chemotherapy if indicated; and if ER-, then only combination chemotherapy. To a great extent, antiestrogens have been substituted in the treatment of breast cancer in postmenopausal women. Estrogens have been administered most widely and induce up to a 30% response; trials with antiestrogens have obtained similar results and thus tamoxifen is being used widely. Also it appears that the effect of treatment is related to the presence of estrogen receptors in the tumor tissue and thus 50-70% of ER+ tumors will respond to estrogens or antiestrogens. Tamoxifen apears to have a lower frequency and milder degree of side effects. Multi-drug therapy has now superseded single drug treatment in the last 5-10 years. If ER status in postmenopausal patients is unknown, the 1st treatment should be chemotherapy for women under age 60-70 and endocrine therapy for the 2nd treatment. In women older than 60-70, the preferred 1st choice therapy should be endocrine. For premenopausal women, those with ER+ tumors, endocrine therapy with tamoxifen should be the therapy of choice; in those with ER- tumors, chemotherapy should be the lst treatment.
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PMID:Principles and indications of endocrine treatment of advanced breast cancer. 736 22

Estrogens can be involved in breast cancer in the following 2 ways: 1) as a promoting rather than a carcinogenic agent in the formation of breast cancers; and 2) as a stimulant to the growth of established breast tumors through the estrogen receptor. The evidence linking estrogen with the etiology of breast cancer is, however, largely circumstantial. Successful endocrine therapy would interfere with the supply of estrogen to the tumor, the nuclear events in estrogen action, or receptor replenishment. The minimal criterion for therapeutic success with endogenous estrogen therapy is to effect a reduction in hormone levels. Only tumors with endocrine sensitivity, indicating the presence of estrogen receptors, will respond, it is believed. The absence of estrogen receptors predicts failure for this type of therapy. Studies have shown that the estrogenic components of OCs (oral contraceptives) do not lead to an increased risk of breast cancer except perhaps in a small subgroup of women already at high risk.
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PMID:Estrogens and breast cancer: present position. 745 74

Estrogens are well known to play a predominant role in promoting the growth of DMBA-induced mammary tumors in the rat. Estrone (E1), a steroid having weak estrogenic activity, is one of most important estrogens in post-menopausal women, where it is converted into the potent estrogen estradiol (E2) by 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) in many peripheral tissues, including the mammary gland. In this report, we have studied the effect of a new antiestrogen (EM-219) (N-butyl, N-methyl-11-(3', 17'beta-dihydroxy-17'alpha-ethinyl-estra-1'3'5'(10'), 14'-tetraen-7'alpha-yl) undecanamide) on E1-stimulated growth of DMBA-induced mammary tumors and compared its effect with that of medroxyprogesterone acetate (MPA) alone or in combination. After 18 days, ovariectomy (OVX) reduced total tumor area to 29.6 +/- 7.1% of the original size, while E1 (1.0 microgram, twice daily) caused a 139 +/- 21% increase in tumor size in OVX animals. MPA (1.5 mg, twice daily) partially reversed the stimulatory effect of E1 to 66.0 +/- 9.0%, while the antiestrogen EM-219 (40 micrograms, twice daily) decreased tumor size to 70.0 +/- 10%. Combination of these two compounds led to a further inhibition of tumor size to 30.7 +/- 7.4% of the value found in OVX animals treated with E1. Tumor E2 levels decreased from 1688 +/- 155 pmoles/kg tissue in OVX animals receiving E1 to 709 +/- 92, 1347 +/- 98, and 184 +/- 11 pmoles/kg tissue in MPA-, EM-219-, and MPA+EM-219-treated OVX-E1 animals, respectively. Treatment of OVX animals with E1 increased by 69% the reductive activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) while MPA abolished completely this effect of E1. In the oxidative direction, treatment with E1, E1 + MPA, or E1 + EM-219 had minimal or no significant effect on the activity of 17 beta-HSD (vs OVX), while the combined treatment with MPA+EM-219 induced a 2-fold increase in 17 beta-HSD activity, thus leading to an increased conversion of E2 into E1. The present data show that combination of the pure antiestrogen EM-219 with MPA exerts a greater reduction in DMBA-induced mammary tumor growth and intratumoral E2 levels stimulated by E1 than either compound used alone. This interactive effect of the antiestrogen and MPA could at least partially be related to the increased inactivation of E2 into E1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibitory effects of medroxyprogesterone acetate (MPA) and the pure antiestrogen EM-219 on estrone (E1)-stimulated growth of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat. 764 32

Estrogens are believed to be major contributors to many cancers of the human female genital tract, but the mechanism of their carcinogenic action is not well-understood. While a tumor-promoting role for estrogens is well-supported, whether they also act as tumor initiators has remained controversial. Here, we have sought to examine the mutagenic potential of diethylstilbestrol, a synthetic estrogen that is a powerful carcinogen in hamsters, and is suspected to be a human carcinogen. Phage M13 single-stranded DNA was treated in vitro with diethylstilbestrol quinone (DES Q: 1.25 mM) and transfected into Escherichia coli cells. DES Q treatment resulted in an apparent enhancement of mutagenesis in the LacZ(alpha) gene segment. DNA sequence analysis of LacZ(alpha) mutants obtained by transfection of DES Q-treated DNA revealed that the major effect of DES Q treatment has been a 6-fold elevation of recombination between the phage-borne LacZ(alpha) sequence and the LacZ delta M15 sequence on the E. coli fertility plasmid F. To confirm whether DES Q treatment is recombinagenic, we used an experimental system that allows the detection of recombination between a defective E. coli chromosomal LacY gene and a normal counterpart borne on a plasmid. Transfection of DES Q (0.06-12 mM) treated plasmid DNA showed significant enhancement (2-100-fold) in recombination, but not in mutagenesis. These results raise the possibility that estrogen quinones may induce recombinagenic DNA damage.
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PMID:Mutagenic and recombinagenic effects of diethylstilbestrol quinone. 769 Aug 89

Estrogens and thyroid hormones contribute importantly to cell proliferation and tumor transformation in the pituitary gland. The purpose of the present article is provide review about neurotransmitters, chemicals, and receptors that are involved in estrogen-induced anterior pituitary growth. Central dopaminergic and noradrenergic systems are thought to be the most important systems in regulation of pituitary growth and function. For this purpose authors discuss some of their past and present data suggesting that estrogen-induced anterior pituitary pituitary growth is associated with decreased synthesis and metabolism of central catecholamines and increased adenohypophyseal dopamine 2 receptors. Treatment with thyroid hormones prevents both estrogen-induced catecholaminergic inhibition and dopamine D2 receptor increment in the anterior pituitary gland. Further studies focusing on central catecholaminergic systems, pituitary receptor equipment and mechanisms of intracellular signal transduction will be of value to better understand pituitary tumor formation and possibly to find new approaches toward treating patients with these tumors.
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PMID:[The role of central catecholamines and dopaminergic receptors in the development of estrogen-induced adenohypophyseal hypertrophy]. 778 47

Estrogens are not carcinogenic. They create however a milieu, which generally stimulates cell division and growth of the target organs, also in cases of existing early neoplastic changes. This growth stimulating effect is dependent on dose and duration of the estrogen effects. Low doses exert no significant influence, medium doses are stimulating, high doses inhibit carcinoma growth, if the tumor is hormone responsive. Cyclic application of a progestogen stops proliferation and induces the specific function of the target tissue. This influence is mediated through a reduction of the number of estrogen receptors, a stimulation of the transformation of estradiol to estrone, a decrease of intracellular metabolism and a reduction of blood perfusion of the target organs. Progestogens therefore act generally preventive against cancer development at the genital organs and probably also on the breast. They should therefore principally be given together with estrogens for at least 10, optimal 12 to 14 days at month. Whether the compromise to give a progestogen only every three or six month will be acting equally carcinoma preventive as the monthly medication, ist not known. In woman bearing risk factors - except proliferative mastopathy - an estrogen-progestogen substitution seems not to increase the inherent risk, rather to reduce it. However nevertheless the manifestation of genital and breast cancer occurs preponderately in women at risk. Familial-genetic immunologic, metabolic factors, weight, race, nutrition, chronic inflammation, regeneration, old age and other risks seem equally or even more important than hormonal factors. Women, who receive a long time estrogen-progestogen substitution, have a lower risk to develop endometrial and ovarian cancer. This is probably also true for mammary and colon cancer. Meta-analyses of all studies could not show so far an increased risk for mammary cancer in estrogen-progestogen substituted postmenopausal women. Women, who receive a postmenopausal long during estrogen-progestogen substitution show statistically a better prognosis of their genital and mammary cancers, if they occur, than unsubstituted controls. Following treated cervical, endometrial and ovarian cancer a strictly indicated estrogen-progestogen substitution is possible without causing drawbacks. The so far valid contraindication against estrogens in post-carcinoma patients does not longer exist. Positive influences on cure rates and survival have been described. In cases of estrogen-progestogen negative receptor mammary cancer cases a substitution is also possible. In all other cases hormones can be given after five years recidive free survival. It is recommended to prescribe not too high doses of estrogens and to combine them with an effective progestogen.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Cancer risk under hormone therapy]. 783 34

Estrogens are the major hormones supporting the growth of human breast cancer. Aromatization of androgen precursors in peripheral tissues, including the breast cancer itself, is the major source of estrogens in postmenopausal women. Therefore, inhibition of the aromatase enzyme offers an effective means of inducing regression of hormone-responsive breast cancer. Aminoglutethimide, the first and most widely tested aromatase inhibitor, suppresses estrogen production to the level of adrenalectomy and exerts an anti-tumor action comparable to other standard endocrine therapies such as tamoxifen. However, conventional doses of the drug (1000 mg daily) cause moderate toxicity and inhibit other critical cytochrome P-450 steroidogenic enzymes, thus requiring concomitant glucocorticoid administration. New non-steroidal, competitive aromatase inhibitors with greater selectivity and less toxicity are being developed. The second generation compound, fadrazole (CGS 16949), lowers estrogen production to a degree similar to aminoglutethimide (50-80%), but at much lower doses (approximately 2 mg daily) and is associated with minimal toxicity. Although not totally specific, this drug is sufficiently selective not to require simultaneous cortisol replacement. CGS 16949 has been shown to possess significant anti-tumor action in pilot studies and is currently being tested in Phase III trials. Recently, a third generation inhibitor, CGS 20267, has been found to have virtually complete selectivity for the aromatase enzyme. Furthermore, this drug suppresses estrogen biosynthesis to a greater extent (approximately 90%) than previously observed with other aromatase inhibitors. Such enhanced activity may lead to a superior anti-tumor action, and may extend the use of this drug to a variety of other conditions where optimal suppression of estrogen biosynthesis is desired.
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PMID:Clinical use of aromatase inhibitors in the treatment of breast cancers. 800 5

Among 67 women with pure gonadal dysgenesis, karyotype 46XY was found in 46 and karyotype 46XX in 21 (26.3% of all intersexual subjects). Karyotype 46XY was either of pure type or mosaicism 45,X/46,XY (10.9%). Primary amenorrhea, underdevelopment of mammary glands and lack or poor development of pubic hair were the main complaints of the patients. In gonadal dysgenesis 46XY mammary glands were developed in 21.8% and pubic hair in 26% suggesting the presence within the gonads of the hormonally active tumor or the state after hormonal treatment. The patients with gonadal dysgenesis 46XX had lowered levels of estrogens and elevated levels of FSH and LH. Karyotype 46XY was not associated with evident changes in hormonal levels. Estrogens were both low and normal, and FSH was elevated (21.5 + 16.6 ug/ml) or normal (3.2-5.0 ng/ml). Total testosterone values were normal or slightly elevated. Such situation can be explained by the presence in some patients of tumors secreting either estrogens or androgens. Taeniform character of gonads was observed by ultrasonography whenever the presence of gonadal tumor was excluded. Histology of specimens taken from gonads or tumors demonstrated the presence of dysgerminoma or gonadoblastoma type of malignancy in 53.1%, foci or proliferation of the Leydig cells in 31.3% and typical morphology of residual gonads without germinal cells only in 12.5%. The differentiation between pure gonadal dysgenesis 46XX and primary ovarian insufficiency is required whenever no characteristic pattern emerges from clinical, hormonal, cytogenetic or ultrasonographic examination. Diagnosis of pure gonadal dysgenesis 46XX can be finally confirmed by the absence of gonocytes in the residual gonad. Besides of removal of gonads or tumors by surgery, the treatment of patients with 46XY karyotype consists in cyclic administration of estrogens and progestagens restoring menstruation and bringing development of secondary sex attributes.
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PMID:[New aspects of diagnosing and treating pure gonadal dysgenesis 46XY and 46XX]. 805 17

The influences of estrogen and progestin on human mammary neoplasia are reviewed with a view to identifying what is known about their effects. Estrogens promote growth of established cancer and pharmacological levels of progestins induce remission. In vivo, highest proliferation of histologically normal mammary epithelium occurs in the progestogenic phase of the menstrual cycle or under the progestogenic influence of oral contraceptives. Little additional hard data exist to indicate whether progestins promote or inhibit human mammary carcinogenesis. Effects on proliferation, steroid receptor content and development are discussed together with interpretation of epidemiological data on risk factors that have hormonal components. Progestins may not be the benign or beneficial agents previously supposed, and there are virtually no data to suggest that they are antiestrogenic. It is hypothesized that carcinogenesis may be accompanied by increased sensitivity to estrogen, which provides a growth advantage to the tumor by maximizing use of the low estrogen concentrations encountered in the postmenopausal state.
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PMID:William L. McGuire Memorial Symposium. Estrogen and progestin effects in human breast carcinogenesis. 826 Jul 28


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