Cases Of Primary Breast Carcinoma Research Articles

Androgen, estrogen, and progesterone receptor levels in malignant and benign breast tumors: a multivariate analysis approach.

Androgens have been frequently used in the treatment of breast cancer. However, objective responses seem to vary according to the steroid hormone receptor expression of the tumor. We have studied the relationship between concentrations of androgen receptors (AR) and those of estrogen (ER) and progesterone (PR) receptors by multiple regression and stratified analysis techniques in 154 cases of primary breast carcinomas and 39 cases of benign tumors. Both the proportion of AR-positive tumors and the concentration of AR were dependent upon the coexpression of ER and PR by the specimens. This association was evident for malignant tumors with predominance of the positive correlation between AR and ER over that of AR and PR in post-menopausal patients. In premenopausal women, ER and PR concentrations were similarly correlated with AR levels. The PR, but not the ER concentration, was positively correlated to AR levels in benign breast tumors. These findings were confirmed by multiple regression, taking into consideration additional information about the patients to build statistical models allowing prediction of AR. Among the other variables considered in building these models--age, menopausal status, weight, height, and clinical stage--only height (using data from all patients) and age (data from post-menopausal women) emerged in addition to ER and PR as significantly explaining the variability of AR as the dependent variable.

Heterogeneity of breast carcinomas determined by flow cytometric analysis.

Eight cases of primary breast carcinoma were studied for evidence of heterogeneity by flow cytometry using propidium iodide staining of DNA. Tumors ranged from 2.5 to 8.0 cm in greatest dimension, mean 4.2 cm. Five to 11 samples, determined by tumor size, were analyzed from each primary tumor in addition to 4 axillary lymph nodal metastases from 3 of the 8 cases. The presence of carcinoma was demonstrated histologically in each flow cytometric sample. Three of the carcinomas showed only diploid DNA content. Three showed the same single hyperdiploid population in each sample. Two carcinomas (2.5 and 3.5 cm) were heterogeneous and demonstrated 2 or 3 hyperdiploid populations. The 2 or 3 distinct hyperdiploid populations were present singly or sometimes in combination in one sample. Five of the 11 samples from 1 of the heterogeneous tumors and its axillary metastasis contained a single diploid population. Therefore, flow cytometric analysis of a single sample from a breast carcinoma may not be representative of the entire tumor. The study of multiple samples of breast carcinomas by flow cytometry is necessary for full characterization of the tumors.

Pregnancy-specific beta-1 glycoprotein (SP-1) in breast carcinoma. Pathologic and clinical considerations.

Ectopic production of placental proteins by a variety of nontrophoblastic epithelial tumors is well recognized. Pregnancy-specific beta-1 glycoprotein (SP-1), a recently described placental protein, has been detected both in the serum and tumors of patients with breast carcinoma. To assess the significance of SP-1 in breast carcinoma, we stained 139 cases of primary breast carcinoma for SP-1 using the immunoperoxidase technique. Overall, 55 (40%) of breast cancers were positive for SP-1; focal positivity was also noted in normal breast epithelium and fibrocystic disease. Both intraductal (32%) and infiltrating duct (43%) carcinomas were more often positive than either in situ (5%) or infiltrating (26%) lobular carcinomas. SP-1 positivity in tumors of infiltrating duct morphology less than 3 cm in diameter, correlated highly (P less than 0.01) with the presence of axillary lymph node metastases. The presence of SP-1 in normal breast epithelium and fibrocystic disease and the low rate of positivity in lobular carcinoma casts doubt on the usefulness of SP-1 as a tumor marker. However, these findings suggest that immunopositivity for SP-1 in small infiltrating duct carcinomas may be an indicator of poor prognosis.

The distribution of carcinoembryonic antigen in breast carcinoma. Diagnostic and prognostic implications.

Carcinoembryonic antigen (CEA) has been shown to be a useful tumor marker in patients with breast carcinoma. The unlabeled antibody immunoperoxidase technique was used to localize CEA in 93 cases of primary breast carcinoma, 15 cases of atypical duct papillomatosis, and 4 cases of duct papilloma. Normal breast epithelium and breast epithelium in fibrocystic disease did not stain positively for CEA. Twenty-four of 27 (88%) intraductal carcinomas, and 47 of 69 (68%) infiltrating duct carcinomas were CEA positive. In contrast, only 5 of 21 (23%) in situ lobular carcinomas and 8 of 24 (33%) infiltrating lobular carcinomas were positive for CEA. All 15 cases of atypical epithelial papillomatosis were negative, whereas 1 of the 4 cases of duct papilloma exhibited microscopic foci of weak CEA positivity. There was a trend for infiltrating duct carcinomas, 3 cm in diameter or smaller, staining strongly positive for CEA, to be associated with synchronous axillary lymph node metastases (P = 0.09). Tumor heterogeneity was a constant feature of CEA staining with positivity varying from region to region and even from cell to cell. Positive immunohistochemical staining for CEA may play an adjunctive role in discriminating intraductal carcinoma from atypical papillary ductal proliferations.

113 Thromboxane and prostacyclin in breast cancer: Effect of medroxyprogesterone acetate (MPA)

Estrogen receptor-negative breast carcinomas are more aggressive and are unresponsive to anti-estrogens. Thus, they clearly require new therapies targeted against specific genes and proteins actively engaged in the pathophysiology of cancer. The S-phase kinase-associated protein Skp2 is required for the ubiquitin-mediated degradation of the cdk-inhibitor p27 and is a bona fide proto-oncoprotein. We attempted to explore whether Skp2 may be a potential specific therapeutic target in the subset of aggressive breast carcinomas by investigating the possible relationship between expression of Skp2 and p27 proteins and estrogen receptor (ER). Immunohistochemical analysis of tumor tissues was employed to determine the expression of Skp2, p27, and ER proteins in 82 cases of primary breast carcinoma. Higher levels of Skp2 were detected more frequently in ER-negative tumors and tumors metastatic to the axillary lymph nodes. The expression of p27 was inverse with the histologic grade. Statistical analysis showed that the percentage of high Skp2 expressors was significantly greater in the group with low p27 expression than in the group with high p27 expression. The current study, together with the results from a previous study, demonstrated the existence of a subtype of high-grade, negative ER breast carcinomas with high Skp2 and low p27 levels. This implies that Skp2 may be a potential specific therapeutic target in a subset of aggressive breast carcinomas. Thus far, there is no specific therapy for the ER-negative and HER-2/neu resistant groups, which are among the subset of aggressive tumors.

Oestrogen receptor assay and morphology of breast cancer

The associations between oestrogen receptors, several morphological features and prognosis were studied in 53 cases of primary breast carcinoma. There was no significant association between oestrogen receptors and any morphological property studied (histological grade, cellularity, fibrosis, elastosis, necrosis, lymphatic permeation, follicular hyperplasia, encapsulation, vascular invasion, tubular areas, histiocytosis, lymphocytic cell infiltration, number of invaded lymph nodes, tumour size, site of recurrence). Disease-free interval and survival were longer in patients having cancers with positive oestrogen receptors. Good prognostic signs were low histological grades, tubular areas and absence of lymphatic invasion within the primary tumour.

Cor pulmonale due to tumour embolism derived from intrasinusoidal metastatic liver carcinoma.

Two cases of primary breast carcinoma are described, both terminating in acute cardiorespiratory failure due to multiple tumour micro-embolism. In both cases the source of the emboli was extensive metastatic intrasinusoidal carcinomatous infliltration of the liver. The association of these two uncommon conditions has not previously been reported. A brief review of the literature pertaining to diffuse intrasinusoidal metastatic carcinomaof the liver and to carcinomatous pulmonary embolism is included. The latter condition may be commoner and of greater clinical significance than his hitherto been appreciated. Some of the factors which may be responsible for this peculiar type of tumour dissemination are discussed.