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

Fourteen 'carcinoid' tumours of the breast are described. They are separable into five with and nine without intracellular mucin. All the tumours are argyrophil, but none is argentaffin. Four tumours studied ultrastructurally contain dense-core granules. Argyrophil carcinomas represent the endocrine analogues of ductal carcinoma in situ, of invasive ductal carcinoma and probably of lobular carcinoma also. Current views vary between the one that the so-called carcinoid is a rare and totally distinct entity to the view, at the other extreme, that it is a very common variant of conventional breast cancer. On the basis of our findings, an intermediate view is justified: argyrophil carcinomas constitute about 5% of breast carcinomas and some varieties at least have non-argyrophil analogues. Factors influencing the prognosis in individual cases are discussed. Argyrophil carcinomas of the breast form a tumour spectrum with a wide range of morphological and histochemical appearances and a variable prognosis.
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PMID:'Carcinoid' tumours of the breast: the morphological spectrum of argyrophil carcinomas. 618 85

Signet ring carcinomas of the breast have been separated recently as an aggressive subtype of breast cancer, distinct from mucinous (colloid) carcinomas. Twenty-four cases of signet ring breast cancer (2% of total breast cancers at the authors' institution) were analyzed. The authors' study indicates that histogenetically such lesions are derived from lobular, not ductal, cells since mucin patterns and ultrastructural features are shared. In addition, in each of our 24 cases, infiltrating lobular carcinoma was identified; in 11 of these (46%) lobular carcinoma in-situ (LCIS) was also noted. Signet ring carcinomas show an unusual metastatic pattern with a propensity to involve serosal surfaces and mimicking gastrointestinal disease or retroperitoneal fibrosis. These tumors are associated with a poor prognosis, with 60% of our 24 patients dead of disease at 7 years. The distinctive clinical and pathologic features of signet ring carcinoma warrant separation of this group of tumors from other forms of breast cancer.
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PMID:Signet ring carcinoma of the female breast: a clinicopathologic analysis of 24 cases. 626 26

Cytotoxic activity towards B-lymphocytes in sera from individuals with breast carcinoma was related to red blood cell cold agglutinin levels and IgM values. The control group consisted of 32 females with a similar age distribution. Significant increases in red blood cell cold agglutinin levels were found in the group of cancer patients and the group with the histological category of mucin-producing carcinoma with lymphocyte cytotoxins (p less than 0.025, respectively), in comparison to the control group and cancer patients without lymphocyte cytotoxins. Serum IgM concentrations were significantly increased in the group of cancer patients (p less than 0.025) and the group with mucin-producing carcinoma (p less than 0.01) with lymphocyte cytotoxins, in comparison to cancer patients and controls without lymphocyte cytotoxins. The lymphocyte cytotoxins were completely or partially adsorbed by red blood cells in 58% of the positive sera. These results suggest that red blood cell cold agglutinins constitute a portion of cytotoxic anti-B lymphocyte antibodies. At present it is unknown whether the lymphocytotoxic antibodies in breast cancer patients are of importance in immunologic host defenses.
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PMID:Red blood cell cold agglutinins and B lymphocyte cytotoxins in breast cancer sera. 629 99

The pathologist has critically important responsibilities as a consultant in the management of patients with breast cancer. The clinical evaluation of the anatomic extent of cancer before treatment, the clinical-diagnostic stage, crudely estimates whether the cancer is localized to the breast, or whether there are regional or distant metastases. The pathologist establishes the diagnosis of cancer microscopically in a biopsy and reports the significant characteristics which can be used in the selection of therapy. The pathologist's additional gross and microscopic examinations after mastectomy, which more precisely document the anatomic extent of the cancer, are the basis of the postsurgical treatment-pathologic stage and provide additional information used to estimate prognosis and determine whether adjunctive therapy is needed. The pathology information used in staging includes the tumor size, histologic type, histologic grade, and presence or absence of axillary of other metastases. These and other pathological factors of significance which are discussed include the gross contour of the tumor as well as the presence or absence of necrosis, and any of the spectrum of cancers that we categorize as "minimal breast cancer" (in situ lobular carcinoma, intraductal carcinoma, invasive carcinoma smaller than 0.5 cm). Furthermore, the prognostic implications of the various histologic types are considered, as well as histologic and cytologic differentiation (grade), multicentricity, vascular invasion, cellular infiltration, and various other factors such as mucin or lipid production, steroid hormone receptors, and the nature of the tumor bed. The presence or absence of axillary lymph node metastases remains the single most significant variable in estimating prognosis for most breast cancers. In addition, combinations of the parameters noted above may have greater prognostic significance than any considered individually. Therefore, the pathologist, through the routine examination and documentation of breast biopsies and mastectomies, can provide important information which can be used to aid in the selection of treatment and in the estimation of prognosis.
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PMID:Pathological parameters useful in predicting prognosis for patients with breast cancer. 637 48

Clinical and pathologic features of five low-grade mucoepidermoid and a similar number of squamous cell carcinomas of breast are presented. Three of each were retrieved from 55 cases of invasive breast cancer previously assessed to exhibit squamous metaplasia. Although the estimated incidence of low-grade mucoepidermoid cancers is approximately 0.2%, they may be more frequent, masquerading under designations of squamous metaplasia or intracystic carcinomas. All patients with low-grade mucoepidermoid cancer, and the two recorded previously, were free of recurrence for 4-10 years. No high-grade mucoepidermoid cancers were found. Squamous cell cancers frequently have a phyllode configuration (carcinoma phyllodes). Two examined by electron microscopy revealed a commonality of ultrastructural features with similar tumors of other sites. None exhibited glandular differentiation or tinctorial evidence of mucin secretion. One squamous cell carcinoma contained both malignant epithelial and banal, osteoclast-like, stromal giant cells. Only the latter were identified in tissue culture. This experience and review of the literature prompted a nosologic characterization of giant cell lesions of breast. One patient with squamous cell carcinoma succumbed because of her disease; the remainder are either free of or alive with recurrence at 4 and 10 years.
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PMID:Mucoepidermoid and squamous cell carcinomas of breast with reference to squamous metaplasia and giant cell tumors. 682 46

This study concerns five different tumour marker assays examined in the context of 94 patients with advanced breast cancer treated in a prospectively randomised trial of different doses of medroxyprogesterone acetate (MPA). MPA was administered at doses of 500 or 1000 mg daily and clinical evaluation of patients was carried out according to UICC criteria. Carcinoembryonic antigen (CEA) was selected as a standard marker, with three assays for MUC1 mucins (epithelial mucin core antigens (EMCA), EMCA2 and BR-MA immunoradiometric assay) differing in antibody specificities for different mucin epitopes. An additional novel assay for soluble cytokeratin was also evaluated as an example of an independent marker with a different nature and biology. Sensitivity of individual assays ranged between 44 (EMCA2) and 69% (cytokeratin) and the use of two assays in combination led to sensitivities as high as 84% (cytokeratin+BR-MA). The proportion of patients found to be assessable by each assay ranged between 51 (EMCA2) and 76% (cytokeratin). Of those patients whose marker changes were assessable, those receiving the higher dose of MPA displayed significant falls in marker levels after 12 weeks of treatment. This effect was not observed in patients receiving 500 mg. The change in cytokeratin levels in patients undergoing high dose MPA therapy proved to be most marked. Using the cytokeratin assay, 91% (of 23 patients) of patients with progressive disease showed at least a 25% rise in serum marker levels. Of these, 66% showed increases before disease progression was detected clinically with a mean lead time of 14 weeks. There was very little difference between the responses of the five tumour marker assays in patients with stable or responding disease, the proportion of these patients with stable or falling tumour marker levels ranging between 58% (CEA) and 77% (EMCA). We conclude that the cytokeratin assay has an application in monitoring response to therapy and predicting tumour progression in advanced breast cancer patients with assessable tumour marker profiles, especially if used in combination with a MUC1 mucin assay.
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PMID:Assessment of five serum marker assays in patients with advanced breast cancer treated with medroxyprogesterone acetate. 748 9

Immunohistochemical analysis of the expression of simple mucin-type carbohydrate antigens (Tn, sialyl-Tn and T) was performed in a series of 43 cases of intraductal hyperplasia without atypia, 9 cases of intraductal hyperplasia with atypia, 54 cases of ductal carcinoma in situ (DCIS) and 26 cases of invasive breast carcinoma. We also studied 36 cases of isolated breast normal epithelium, 20 cases of "normal" breast epithelium adjacent to neoplasms and 14 cases of apocrine metaplasia. All antigens were detected in different frequencies in normal, hyperplastic, metaplastic and neoplastic breast epithelium. Tn and sialyl-Tn are expressed more frequently in malignant than in benign breast epithelium; while Tn expression increases from normal to invasive carcinomas, sialyl-Tn increases until DCIS and drops in invasive carcinomas, suggesting that either there is a failure of a proportion of DCIS to progress to invasive carcinoma or loss of expression of sialyl-Tn when some carcinomas become invasive. The high frequency of Tn and sialyl-Tn expression in breast intraductal proliferations probably reflects incomplete glycosylation in these lesions, which is a well-known tumour-associated phenomenon and supports the assumption that such lesions are putative precursors of breast cancer. T antigen was expressed in all groups studied, but its prevalence differed significantly between normal and neoplastic epithelium. The expression of these antigens in epithelium adjacent to carcinomas is similar to that found in isolated normal breast epithelium, whereas apocrine metaplasia has a pattern of simple mucin-type glycosylation that is specific and distinct from that of the normal breast epithelium, with a high frequency of marked expression of Tn and sialyl-Tn. The similarity of the pattern of expression of simple mucin-type antigens in metaplasia and malignant neoplasia reduces the usefulness of these markers from a diagnostic standpoint.
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PMID:Simple mucin-type carbohydrate antigens (T, sialosyl-T, Tn and sialosyl-Tn) in breast carcinogenesis. 749 93

Using synthetic peptides 60,80, and 105 residues long, corresponding to 3, 4, and 5.25 tandem repeats of human mucin MUC-1 protein core, as antigens in a solid-phase enzyme-linked immunosorbent assay, we screened sera from 24 breast cancer patients, 10 colon cancer patients, and 12 pancreatic cancer patients, at various stages of disease, for the presence of mucin-specific antibodies. The 105-residue peptide was superior in allowing detection of high levels of anti-mucin antibodies in 10.9% of sera in each cancer group. Another 4.3% showed intermediate reactivity. Lower levels of detection were achieved with the 80-residue peptide, and no specific reactivity was detectable with the 60-residue peptide. Anti-mucin antibodies were previously undetectable when this assay was performed with purified whole mucin or short synthetic peptides. The presence or absence of antibody did not correlate with the levels of circulating mucin or stage of disease. One highly reactive serum sample was used to identify more precisely the epitope on the long synthetic peptide to which the reactivity was directed. The reactivity of this serum specific for the 105-residue peptide was blocked by a 9-residue peptide from the NH2-terminal region of the 20-residue tandem repeat containing the previously identified immunogenic epitope APDTRP. Another 9-residue mucin peptide, from the COOH-terminal region of the tandem repeat which does not contain the APDTRP epitope, had no effect. All the mucin-specific reactivity was found to be of the IgM isotype, indicating a helper T-cell-independent response, unusual for an antibody against a peptide epitope, but not unexpected for tandemly repeated epitopes.
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PMID:Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreatic, and colon cancer patients. 751 93

Several investigators have shown that the expression of the sialyl-Tn (STn) epitope on cancer associated mucins is associated with a poor prognosis in several human cancers suggesting that STn may have functional significance in metastasis. We postulate that antibodies against the STn-epitope can inhibit metastasis. We generated a synthetic "mimic", NANA alpha (2-->6)GalNAc alpha-O-Crotyl (STn-crotyl), of the natural O-linked epitope on mucins, NANA alpha (2-->6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm and a "vaccine" containing STn-KLH plus Detox adjuvant was formulated. The immunogenicity of the vaccine was evaluated in BALB/c mice and in metastatic breast cancer patients. The specificity and titres of IgG antibodies were evaluated by ELISA on ovine submaxillary mucin (OSM) solid phases. OSM is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 microgram of STn-KLH produced a median IgG titre of over 1:5000 on solid phase OSM. Anti-OSM IgG monoclonal antibodies generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens. Breast cancer patients immunized 2-8 times with 25 or 100 micrograms of the same vaccine produced median peak IgG titres 1:1280 measured on STn-HSA and 1:80 on OSM. Once again, hapten inhibition experiments with the human sera demonstrated the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not against several other related synthetic haptens. We found little or no evidence that the artificial linker arm (crotyl linker) contributed significantly to either the titre or affinity of the antibodies generated in either mice or human breast cancer patients. This suggests that the antibodies recognized the cancer-associated disaccharide NANA alpha (2-->6)GalNAc. Evidence of a clinical response was noted in several of the immunized breast cancer patients with other patients showing prolonged disease stability.
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PMID:Specificity of the IgG response in mice and human breast cancer patients following immunization against synthetic sialyl-Tn, an epitope with possible functional significance in metastasis. 752 78

The tumor-associated mucin-glycoprotein TAG-12 is strongly expressed in approximately 96% of all breast cancer patients and nearly 68% of all ovarian cancers. The experimental results of this work indicated that humoral immune response against TAG-12 is possible. Immunization with anti-idiotypic monoclonal antibodies produces this response. In this experiment, anti-idiotypic monoclonal antibodies represent the internal image of a specific epitope on TAG-12. Monoclonal antibody (MAb) 12H12 was selected to produce anti-idiotypic antibodies (anti-Ids) because of its high reactivity with TAG-12. Syngeneic murine anti-Ids were developed by immunization of BALB/c mice with the 12H12-Fab-KLH conjugate. A competitive assay with purified TAG-12 was utilized to identify anti-Ids with mirror image function. Two MAbs with "internal image" specificity were selected, 5H8 and 5H2. Two New Zealand White rabbits were immunized with 5H8. Serum samples tested 6 weeks after the initial immunization showed comparable titers against TAG-12. The binding capacities of the rabbit sera to different human breast as well as nonbreast cancer cell lines demonstrated strong binding with TAG-12-positive breast cancer cell lines. Competitive inhibition assays demonstrate that Ab3 and purified TAG-12 totally inhibit the binding of 12H12 antibody to TAG-12-positive cells. No inhibition was detectable with unrelated MAbs or normal mouse immunoglobulin. Binding assays with polyclonal Ab3 serum and several human cancer cell lines showed reactivity to nearly every tested cell line. Soluble TAG-12 showed no inhibition, indicating that this binding is due to a different set of idiotypes. Anti-Id 5H8 elicited an immune response to TAG-12. Utilization of anti-Id as a vaccine against the breast cancer-associated tumor antigen TAG-12 was successfully demonstrated in a xenogeneic animal model.
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PMID:Production of mouse monoclonal anti-idiotypic antibodies specific to epitopes of tumor-associated mucin TAG-12. 753 53


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