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

Five tumor markers can be simultaneously determined in the serum by radioimmunoassay: carcinoembryonal antigen (CEA), alpha-fetoprotein (alpha-FP), human chorionic gonadotropin (HCG), beta-subunit of HCG (beta-HCG) and kappa-casein. In a series of 935 healthy subjects, these antigens remain detectable or are detected within very precise limits. At the start of the clinical evolution of breast cancer, the incidence of pathological concentrations is increased as compared with the highest level observed in normal subjects. This high incidence is mainly due to a concomitant determination of CEA, kappa-casein, HCG and beta-HCG. The alpha-FP test is never positive, while the kappa-casein concentration is particularly high in the first clinical stages of breast cancer and with metastases. The concomitant determination of these tumor markers may be a biological element contributing to the diagnosis of neoplasia, although it is neither an absolute nor a specific criterium. Indeed, a pathological concentration of at least one antigen was observed in 5.5% of the subjects presenting with benign mastopathy. When metastases occur (25 patients), the incidence of pathological concentrations of at least one antigen increases: 88%, the absolute values of these levels increasing simultaneously. The determination of the antigen concentration therefore allows an evaluation of the extension of the disease. Surgical removal reduces the incidence of positivity of these antigens to 34%. Persistence of pathological levels seems to be related to a possibility of relapse or metastatic spreading. Finally, chemotherapy and radiotherapy applied on a tumor which is not excised, does not decrease the incidence of positivity of the tumoral markers, although their levels seem to fluctuate with the clinical evolution.
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PMID:Casein and other tumor markers in relation to cancer of the breast. 7 72

The urinary testosterone levels of 40 premenopausal and postmenopausal patients with advanced breast carcinoma were assayed before and after ovariectomies. Histologic examination of the ovaries of 25 patients whose hormone levels were above normal revealed interstitial cell hyperplasia. Two months after the operations, the amounts of testosterone excreted by the womaen decreased significantly. We considered this as indirect evidence that the ovaries contributed to androgen synthesis. However, 15 patients had normal hormone excretion values that did not change 2 months postoperatively. Testosterone levels for 6 of the women 5 months after surgery were higher than at the previous testing. We surmised that the increased gonadotropic activity that followed ovariectomy migh have stimulated adrenal androgen secretion. To elucidate this point, we gave injections of 15,000 IU human chorionic gonadotropin (HCG) to breast cancer patients who were free of any recurrence and, 3 or 24 months previously, had undergone prophylactic ovariectomies (5 and 4 patients, respectively). In 5 of these women, the amount of testosterone excreted increased significantly after HGG was administered. We inhibited adrenal androgen secretion in 11 patients, whose presurgical urinary testosterone levels were above normal. After their ovaries were removed, these women received 1.5 mg dexamethaxone (DXM) daily for 30 days at a time, after which the amount of testosterone excreted was evaluated and, if the level was above 5.0 mug/24 hours, therapy was repeated for another 30 days. Of the patients who showed objective remission after ovarietomies, there were 4 (26.3%) of 15 who had normal androgen excretion levels; 8 (57.1%) of 14 had increased amounts and were treated by surgery alone; and 10 (90.9%) of 11 received a combination of ovariectomies and DXM therapy. The duration of regression was the highest in the latter group.
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PMID:Ovariectomy alone or in combination with dexamethasone in patients with advanced breast cancer and high levels of testosterone excretion. 94 53

An important question in the management of patients with cancer is early identification of the individual who following 'curative' primary therapy will develop recurrence. Another question is which of several alternative treatments is most appropriate. If the patient at risk can be identified early more aggressive and appropriate adjuvant chemotherapy can be initiated to insure remission or longer periods of disease free survival. In this review the role of tissue and/or serum enzyme activities in this regard is considered. Enzymes alone or in combination with tumor markers or other factors may be used. Lactic dehydrogenase (LDH) is perhaps the most common clinical enzyme used in cancer patients for prognostic purposes. It has an important role in germ cell tumors and in association with chorionic gonadotropin and can predict response to therapy and the prospects of remission. LDH is a valuable prognostic marker in lymphoma, leukemia and in colon cancer. Patients can be stratified into treatment protocols based on LDH activity. The stage of cellular proliferation can be evaluated by assay of thymidine kinase in the serum of patients with Hodgkins Disease and in Lymphoma. An important new marker, Cathepsin D in breast tissue may be useful in predicting women with breast cancer who are at risk for early recurrence.
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PMID:Enzymes as prognostic markers and therapeutic indicators in patients with cancer. 157 80

The role of hormones, especially progesterone and synthetic progestins, in the pathogenesis of breast cancer is highly debated and far from being clarified. The observation that differentiation of the mammary gland prior to exposure to a carcinogenic agent inhibits the initiation of mammary carcinomas, and the fact that this protection is mediated by cell kinetic changes induced in the gland parenchyma by hormonal stimuli such as that of pregnancy, led us to determine how ovariectomy and hormonal supplementation affect the cell kinetic characteristics in various terminal ductal structures of an intact animal mammary gland, i.e., terminal end buds, terminal ducts and alveolar buds. Fifty-day-old virgin Sprague-Dawley rats were either ovariectomized or treated for 21 days with norethynodrel and mestranol or medroxyprogesterone acetate in doses of 0.5 mg (low dose - LD), or 5.0 mg (high dose - HD); chorionic gonadotropin (hCG) in doses of 1 or 100 IU/day, or placental lactogen (PL) in a dose of 0.5 mg. Cell kinetics were studied by counting the number of cells incorporating [3H]-thymidine and expressed as the DNA labeling index. In the intact animal, the rate of cell proliferation was highest in terminal end buds, decreased progressively towards the ductal portions and was even lower in alveolar buds. Ovariectomy significantly reduced the proliferative activity of the mammary epithelium, ten-fold in terminal ducts and alveolar buds, and five-fold in terminal end buds. DNA labeling index was significantly reduced in terminal ducts and alveolar buds by all hormones at all doses, except PL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Progestagens and mammary gland development: differentiation versus carcinogenesis. 183 45

A collaborative immunohistochemical study was carried out to examine the expression and prognostic significance of tumor markers in a retrospective series of 233 invasive breast carcinomas. The patterns of tumor marker expression in 94 patients with short remission duration (recurrence within five years) were compared with 50 patients with intermediate (at five to ten years) and 89 patients with long (no recurrence at ten years or longer) remission durations. The antigens examined were carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), placental lactogen, alpha-lactalbumin, and pregnancy-specific beta-1 glycoprotein. Carcino-embryonic antigen was the most frequently expressed antigen, whereas HCG was demonstrated least frequently. Also, the ABH isoantigen status was examined using monoclonal antibodies; isoantigen expression was observed in a subset of breast carcinomas, contrary to previous reports of total deletion in breast cancer. Two of the markers, CEA and HCG, were examined by both laboratories, each with two different antisera and also with both PAP and ABC immunohistochemical technics. Meticulous efforts were taken to provide quality control and ensure reproducibility of results. These included the use of serial sections of duplicate pathologic material by both institutions, standardization of experimental conditions and interpretation criteria, double-blind evaluation of exchanged slides, and use of standardized data sheets to record staining extent and intensity. No significant disagreements were observed between data obtained through the different approaches. The steps that were taken to minimize interobserver and interinstitutional differences in this study are presented as a model for collaborative immunohistochemical studies. The expression of tumor markers, alone or in combination, was not found to bear any significant relationship to prognostic indicators, such as the likelihood of recurrence, interval before recurrence, or presence of metastasis.
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PMID:Tumor marker expression in breast carcinomas and relationship to prognosis. An immunohistochemical study. 387 77

Laboratory measurements can be used to detect, classify, and monitor patients with breast cancer. This review covers in detail the clinical usefulness of carcino embryonic antigen, tissue polypeptide antigen, various glycoproteins, pregnancy-associated proteins, casein, lactalbumin, beta-2-microglobulin, ferritin, immunoglobins, acute phase proteins, placental-like alkaline phosphatase, liver-associated enzymes, glycosyltransferases, human chorionic gonadotropin, calcitonin, polyamines, and collagen breakdown products, in relationship to their diagnostic utility in patients suspected of having or known to have breast cancer. In addition, these authors assess the merits of various multivariate techniques using a number of clinical chemistry quantities in the same regard. Finally, the relative contribution of biochemical tests vs. the information values gained from "surgical pathology" data (number of positive nodes, number of negative nodes, and degree of anaplasia) is discussed.
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PMID:Usefulness of clinical chemistry measurements in classifying patients with breast cancer. 674 28

There are an estimated 8-10 million oral contraceptive (OC) users in the U.S. Investigation of the effects of OCs on neoplasia is not easy; currently 4 investigative methods are used: 1) case reports, 2) disease rate and trends, 3) case-control studies, which are the main source of careful retrospective information, and 4) cohort studies, which compare the incidence of disease in patients exposed to suspected environmental factors, and in those who are not exposed. Major risk factors for carcinoma of the breast are female sex, age, genetic predisposition, previous benign breast disease, and previous cancer of one breast; undetected breast cancer may be present for many years before diagnosis, and risk is increased in patients with chronic cystic mastitis or fibrocystic disease of the breast. Clinical observations have suggested a strong association between endocrine influence and the incidence or progression of breast cancer; current evidence tends to support the role of estrogens in the etiology of carcinoma of the breast with respect to long-term estrogen administration, but this evidence is not valid for young patients who are on combined OCs. Most studies have documented a decreased risk of benign breast disease with length of OC use persisting for 4 years; these studies, however, did not analyze lesions by histologic type. Studies that show a protective effect on benign disease do not show the same protective effect for breast cancer. Data from cohort studies show no association of OCs with breast cancer. Since 1972 a number of reports have associated OCs with liver tumors, stating that risk increases with duration of use. A national survey revealed that the frequency of malignant tumors increased with age, but that the frequency of benign lesions had a peak in the 26-30 age group which corresponds to increased use of OCs. Benign tumors are dangerous because they tend to rupture spontaneously. The association between pituitary adenoma, causing postpill amenorrhea, and OC use is very controversial. OC use may also cause endometrial hyperplasia; postmenopausal estrogen use has also been associated with endometrial carcinoma, although the causal relationship has never been proven; progestogens may be useful in the therapy of some endometrial carcinomas. Carcinoma of the cervix seems to be more influenced by age at 1st intercourse and by multiple sexual partners than by OC use; several case-control studies have shown that there is no significant difference between incidence among OC users and nonusers. Data about the association between OCs and ovarian carcinoma are reassuring but incomplete. OCs should not be used in patients with positive chorionic gonadotropin titers who have been treated for hydatidiform mole.
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PMID:Neoplasia and hormonal contraception. 702 11

Studies of the induction of mammary tumors by 7,12-dimethylbenz(a)anthracene in a rat model show that human chorionic gonadotropin (hCG) administration reduces tumor incidence in a manner comparable to that of a completed pregnancy. On the basis of their studies, Russo and Russo (Cancer Epidemiol., Biomarkers & Prev., 3: 353-364, 1994) have proposed that hCG treatment of young nulliparous women would reduce their breast cancer risk in a manner similar to that of a term pregnancy. As part of a population-based, case-control study of breast cancer among women ages 40 years or younger, we asked women whether they had received hCG injection as part of a weight loss regimen or as a component of infertility treatment. Participants in this study were 744 women newly diagnosed with breast cancer between July 1983 and December 1988 and 744 controls individually matched on birthdate (within 36 months), race (white), parity (nulliparous/parous), and neighborhood of residence. Forty-five cases and 65 controls reported exposure to hCG (multivariate odds ratio = 0.77, 95% confidence interval = 0.50-1.19). Risk was reduced significantly among women whose maximum nonpregnant body mass index was less than 27.5 kg/m2 but no reduction in risk was observed among more obese women. Although the odds ratios were reduced substantially for both nulliparous and parous women with maximum nonpregnant body mass indices less than 27.5, only the result for nulliparous women was statistically significant. These results are consistent with the effects proposed by Russo and Russo based on their animal model. Although not definitive, these results suggest that hCG may be a means for reducing breast cancer risk.
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PMID:Treatment with human chorionic gonadotropin and risk of breast cancer. 754 96

Breast cancer, the most frequent malignancy diagnosed in women, continues to increase in incidence in all industrialized nations. The fact that this disease becomes incurable once it has spread to regional or distant sites indicates that its complexity is beyond our present level of knowledge. A better understanding of the etiopathogenesis and biology of breast cancer is required in order to develop a rational basis for its prevention and therapy. The observation that early parity reduces the risk of developing breast cancer indicates that reproductive and hormonal conditions might play an important role in its prevention. The elucidation of the mechanisms mediating this protection requires the availability of adequate experimental models. The induction of rat mammary carcinomas with chemical carcinogens has proven to be useful for these purposes, especially since, in this model, full-term pregnancy or treatment of virgin rats with a placental hormone, human chorionic gonadotropin (hCG), prior to the administration of the carcinogen protects the mammary gland from tumor development. Since both pregnancy and hCG treatment induce differentiation of the mammary gland, this process is considered to be essential for the inhibition of the neoplastic process. The possibility of preventing breast cancer by treating young nulliparous females with hormones that mimic a full term pregnancy is of practical interest to the human female population, but it requires a thorough knowledge of the development of the human breast. Our studies indicate that the breast of postpubertal nulliparous women is composed of lobular structures reflecting different stages of development. Type I lobules are the most undifferentiated. Type 2 lobules evolve from the previous ones; they are composed of a higher number of ductular structures per lobule. They progress to lobules types 3 and 4, which are present in the breast during pregnancy and lactation. The type 1 lobule, considered to be the site of origin of ductal carcinomas, predominates in the breast of nulliparous women of all ages. In parous women, the type 3 lobule is the most frequent. Primary cultures derived from breast tissues composed of type 1 lobules express phenotypes of cell transformation not observed in cells derived from type 3 lobules. These data acquire relevance in the light that women with a history of early pregnancy are at a lower risk of developing breast cancer than nulliparous women, an effect attributed to differences in the degree of differentiation of the breast. Pregnancy furthers the differentiation of type 1 lobules to type 3, making them refractory to neoplastic transformation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The etiopathogenesis of breast cancer prevention. 772 46

Early trophoblastic cells share several features with neoplastic cells. Based on that observation, we attempted to identify genes overexpressed in tumors by analyzing genes preferentially expressed in trophoblasts. A subtracted library enriched in complementary DNA from early cytotrophoblasts was constructed, and the expression level of selected recombinants was analyzed on a large panel of normal and tumor tissues. The library was prepared using a polymerase chain reaction-based complementary DNA subtraction method with 6-week amenorrhea cytotrophoblast endoplasmic reticulum-bound RNA as target, and a mixture of complementary DNA prepared from terminal placenta and activated T-lymphocytes as driver. Two rounds of screening were performed to isolate clones preferentially expressed in early placenta. From a total number of recombinant clones estimated at 32,000 in the subtracted library, 594 inserts were analyzed by Southern blot and 21 sequences were isolated as corresponding to genes highly expressed in early placenta. Eleven encoded known molecules, such as carcinoembryonic antigen, human chorionic gonadotropin, and mitochondrial rRNAs. Ten sequences represented novel genes. Northern blot analysis confirmed that most of these genes were preferentially expressed in early trophoblast in comparison to terminal placenta. Three clones that gave detectable hybridization signals on total RNA were extensively studied and were found to be overexpressed in various tumors. Two of these clones, designated B9 and E4, were later identified as corresponding to genes coding for the putative ribosomal protein S18 and the bifunctional enzyme ADE2H1 involved in purine biosynthesis, respectively. Expression of the third clone, E9, was increased up to 10-fold in breast cancer tissues in comparison with normal counterparts. Present results confirm that many genes expressed in the trophoblast are overexpressed in malignant cells. This approach could provide a general targeted method for the identification of genes overexpressed in various neoplastic cell types.
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PMID:Identification of genes overexpressed in tumors through preferential expression screening in trophoblasts. 792 43


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