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

Breast cancer is one of the common cancers and is a leading cause of cancer mortality in women. The TG.NK transgenic mouse line on FVB strain background expresses the c-neu oncogene under the control of a MMTV promoter in mammary tissue and appears to be a useful animal model for evaluation of strategies to delay or prevent mammary cancer. Fiber-rich nonpurified diet (NTP-2000) and some retinoid analogues have delayed mammary cancer in the TG.NK model. Four week old hemizygous TG.NK female mice with MMTV/c-neu (erbB2) activated oncogene were fed NTP-2000 diet containing the retinoid analogue 4-hydroxyphenylretinamide (4-HPR) at 7 mmol/kg or the arotinoid Ro 40-8757 at 1.5 and 2.5 mmol/kg for 26 weeks. The 4-HPR at 7 mmol/kg diet delayed the development of palpable tumors up to 24 weeks, but by 26 weeks, the incidence markedly increased and was closer to the NTP-2000 diet control group. However, the 4-HPR diet markedly decreased the average weight of the tumors at 26 weeks with no decrease in multiplicity. The 4-HPR also caused significant increase in liver weights without an effect on body weight. Arotinoid Ro 40-8757 caused marked decrease in the number and branching of mammary ducts, and inhibited mammary tumor development with significant decrease in the incidence, multiplicity, and tumor weights compared to the NTP-2000 diet control. Arotinoid also caused a significant dose-related increase in liver weights without a significant effect on body weights. At the doses tested, the arotinoid but not 4-HPR decreased the circulating levels of IGF-1. However, there was no association between the IGF-1 levels and the size, incidence, or absence of tumors when evaluated for any treatment group or for all mice in the study irrespective of treatment. The oncogene erbB2 (c-neu) and the growth factor EGF expression were more prominent in the small tumors of the mice treated with arotinoid than in the larger tumors of the control group. PCNA staining was observed in areas where there was high erbB2 and EGF staining. The delay in onset of mammary tumors by the above retinoid analogues may be related to the delay in development of mammary glands.
Breast Cancer Res Treat 1999 Dec
PMID:Changes associated with delay of mammary cancer by retinoid analogues in transgenic mice bearing c-neu oncogene. 1071 86

The potential of aromatase (estrogen synthetase) within the breast to provide a significant source of estrogen mediating tumor proliferation is suggested by studies reporting 4- to 6-fold higher estrogen levels in tumors than in plasma of postmenopausal patients with breast cancer. Recent studies in our laboratory have identified aromatase and its mRNA in tumor epithelial cells using immunocytochemistry and in situ hybridization. In addition, significant aromatase activity, which was stimulated 7-fold by dexamethasone, was measured in metastatic cells isolated from a breast cancer patient. Increase in proliferation, as measured by proliferating cell nuclear antigen immunostaining in tumor sections and by thymidine incorporation into DNA in response to testosterone, was observed in histocultures of breast cancer samples. This latter effect could be inhibited by 4-hydroxyandrostenedione. These results imply that intratumoral aromatase has functional significance and may be an important target for successful inhibitor treatment of breast cancer patients. To investigate treatment strategies with aromatase inhibitors and antiestrogens, we developed an intratumoral aromatase model to simulate the hormone responsive postmenopausal breast cancer patient. Tumors of estrogen receptor positive human breast carcinoma cells (MCF-7) transfected with the human aromatase gene are grown in ovariectomized nude mice. These cells synthesize sufficient estrogen to stimulate tumor formation. We have utilized this model to investigate the effects on tumor growth of the antiestrogens, tamoxifen and ICI 182780, and the aromatase inhibitors, letrozole and anastrozole (arimidex), alone and in combination. Both the aromatase inhibitors and the antiestrogens were effective in suppressing tumor growth. However, letrozole was significantly more effective than the antiestrogens. When the aromatase inhibitors were combined with the antiestrogen, tamoxifen, tumor growth was suppressed to about the same extent as with the aromatase inhibitors alone. Furthermore, the results do not suggest any benefit from combining tamoxifen with the pure antiestrogen, ICI 182780. Thus sequential use of these agents is likely to be more advantageous to the patient in terms of longer duration of effective treatment.
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PMID:Aromatase inhibitors and their antitumor effects in model systems. 1073 Nov 10

Studies of the mechanism of actions of estrogen, antiestrogen and physical factors may provide clues to an understanding of breast cancer growth and/or regression regulation and thus identify novel targets for therapeutic intervention. Defective control of apoptosis appears to play a central role in the pathogenesis of neoplasia. Conversely, cancer therapy and ionizing radiation can induce cancer cell death by apoptosis and/or necrosis. bcl-2 gene and p-53 gene products have been both linked to programmed cell death pathways. We have analyzed the effect of estradiol, tamoxifen and UV exposure on the induction of apoptosis, expression of p53 and bcl-2 gene products as well as the proliferative activity (expressed as [3H]thymidine incorporation and PCNA and MPM2 antigens involvement) in MCF7. It has been found that estradiol increases the speed of cell cycle in MCF7 and acts as antiapoptotic factor. Tamoxifen has multiple influence on the rate of growth of cancer cells: depends on estrogen receptor (ER), conducts reduction of proliferation rate; depends on ER and other mechanisms conducts to suppressions of Bcl-2 protein expression and induction of cell death through apoptotic pathway. Estradiol prevents the apoptotic influence of tamoxifen probably by enhancement of Bcl-2 protein expression and does not prevent the inhibition of proliferation rate. The irradiation with UV induces apoptosis by over-expression of p53 and down-regulation of bcl-2 gene.
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PMID:Influence of estrogen, antiestrogen and UV-light on the balance between proliferation and apoptosis in MCF-7 breast adenocarcinoma cells culture. 1087 Jun 82

The purpose of the present study was to estimate p53 and c-erbB2 expression in an Egyptian cohort and assess their relationships with other indicators of aggressive disease. Additionally, the frequency of both oncogenes was compared to that reported in other breast cancer populations. Paraffin-embedded tissue sections obtained from 210 invasive ductal carcinomas were evaluated immunohistochemically for p53 and c-erbB2 oncoproteins using CM-1 polyclonal antibody and mAb1 monoclonal antibody, respectively. Tumor proliferation was also assessed using PC10 anti-PCNA (proliferation cell nuclear antigen) monoclonal antibody. Chi square test was used to assess the relationship between p53 and c-erbB2 and their associations with other prognostic factors. The results revealed that p53 and c-erbB2 were equally expressed, each accounting for 40% of the total cases (84 out of 210) Immunoreaction for p53 and/or c-erbB2 was demonstrated in 65% (136 out of 210) and 15% (32 out of 210) were positive for both oncogenes. Poor histologic grade was more significantly associated with p53 expression (P = 0.0001) than c-erbB2 expression (P = 0.01). The latter was also significantly associated with premenopausal status (P = 0.01) and large tumor size (P = 0.003). Both p53 and c-erbB2 oncoproteins were found to be unrelated to each other, nodal status or PCNA immunostaining. These data suggest that p53 and c-erbB2 oncogenes correlate with poor prognostic features of breast cancer. The differences between the frequency of p53 and c-erbB2 expression observed in this study and in the reports of Western authors will hopefully stimulate investigation of these oncogenes using molecular biologic techniques and matched comparative Egyptian and European breast cancer groups.
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PMID:Immunohistochemical expression of p53 and c-erbB2 proteins in breast cancer in Egypt. 1092 68

To identify the characteristics of cases with an wide intraductal cancerous extension (WICE), we examined the relationship between WICE and type IV collagen distribution, and the relationship between WICE and the content of the proliferation-associated proteins in human breast cancer. The immunohistochemical distribution of type IV collagen and proliferating cell nuclear antigen (PCNA) were investigated in formalin-fixed tissue sections from 21 breast cancer cases. We demonstrated a significant correlation (p=0.014) between the presence of WICE and immunostaining of type IV collagen in the cancerous ducts (ducts occupied by cancer cells) in the central invasive area of breast cancer. However, no correlation was found between the presence of WICE and the PCNA index (percentage of positive cells per 1000 tumor cells). These findings suggest that the lack of the process of the loss of type IV collagen in the duct wall is more important than the nature of the tumor cells in the development of WICE.
Breast Cancer 1994 Jul 30
PMID:Significant Correlation between the Presence of Type W Collagen in the Duct Wall and the Development of Wide Intraductal Cancerous Extension in Breast Cancer. 1109 4

In the recent years several studies have shown that about 30% of cases with axillary node-nagative breast cancer suffer relapse of the disease. Our attempt was made to evaluate the most significant prognostic factors to predict this high risk group which may be benefited from adjuvant treatment. For this purpose, we selected 9 patients out of 80 cases of node-negative breast cancer who had been followed up at least for 5 years and had the recurrence of the disease. For comparison, 16 patients from the same group who did not have relapse were selected on a random basis. Histology, receptor status, AgNOR, DNA flow cytometry and various immunohistochemical parameters were compared between the groups with recurrence and that without recurrence. On univariate analysis, tumor size, immunohistochemical expressions of PCNA, MIB-1, c-erbB-2 and S-phase fraction were significantly different between the above two groups. By multivariate analysis, immunohistochemical c-erbB-2 expression (more than 50% of cancer cells) was an independent parameter. As a summary from our studies, c-erbB-2 immunohistochemical staining on paraffin sections might be the best independent prognostic factor in axillary node-negative breast cancers.
Breast Cancer 1995 Apr 30
PMID:Clinical and Histological Prognostic Factors in Axillary Node-Negative BreastCancer: Univariate and Multivariate Analysis with Relation to 5-Year Recurrence. 1109 32

We recently encountered a 6-year-old girl with a malignant phyllodes tumor of the breast. The patient's mother noticed a tumor on the right breast of her first doughter at 8 months after from her birth. The baby was brought to the Second Depertment of Surgery, University of Tokushima, at age 20 months. We recommended removal of the 3.5 x 2.9 cm tumor in the right breast, but it was not done. Next, she visited our department at 6 years of age because the tumor had gradually enlarged, reaching a size of 4.3 &timus; 4.0 cm. She underwent excisional resection of the tumor, and the tumor was diagnosed as a malignant phyllodes tumor of the breast coexisting with a borderline phyllodes tumor. To our knowledge, this is the youngest reported case of a malignant phyllodes tumor of the breast. Moreover, the malignant lesion was positive for estrogen receptor (ER) and showed strong proliferating cell nuclear antigen (PCNA) staining. On the other hand, the borderline part was negative for ER and showed weak PCNA staining. Thus, in the present case, the expression of ER, the exposure to estrogen (for example, the mother's estrogen during gestation) and increase in the proliferation rate may have played important roles in the mechanism of the transformation of the phyllodes tumor.
Breast Cancer 1995 Apr 30
PMID:A Malignant Phyllodes Tumor of the Breast in a 6-Year Old Girl. 1109 35

BACKGROUND: This study was undertaken to determine the absolute and relative value of angiogenesis, proliferating cell nuclear antigen (PCNA) and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. PATIENTS AND METHODS: Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including angiogenesis, PCNA using per-manent-section immunohistochemistry, clinicaltumor size, histological grade (HG), tumor necrosis, lymphatic vessel invasion (LVI), histological extension, histological classification, and infiltrating growth (INF), followed for a median of 10 years (range, 1 to 20). RESULTS: Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that PCNA, clinical tumor size, HG, angiogenesis, and LVI were significantly predictive of 20-year RFS or OS. Tumor necrosis was significantly predictive of OS, not of RFS. Multi-variate analysis showed that clinical tumor size (P = 0.0003), angiogenesis (P = 0.0003), PCNA (P = 0.0064), and HG (P = 0.0401) were significant independent prognostic factors for RFS. PCNA (P< 0.0001) and clinical tumor size (P = 0.0112) were significant independent prognostic factors for OS, while angiogenesis was a borderline significant factor. CONCLUSION: PCNA and angiogenesis were important new prognostic factors in node-negative breast cancer patients.
Breast Cancer 1999 Oct 25
PMID:New Prognostic Factors Associated with Long-term Survival in Node-Negative Breast Cancer Patients. 1109 46

Multicentric breast carcinomas not diagnosed clinically, were examined by serial step-cut sectioning of the whole breast, and multicentric carcinoma cases were compared with single carcinoma cases with regard to histological and clinicopathological findings. In 7(3.7%) out of 187 surgically resected breasts, latent carcinomas apart from the main carcinoma were noted. The size of the latent carcinoma varied from 0.2 to 5 cm in diameter. The histological type was noninvasive ductal carcinoma in six cases and invasive ductal carcinoma in one case. When the main carcinoma was small in size (less than 2.5 cm in diameter), and showed papillotubular carcinoma as the histological type or had estrogen receptor (ER) by the dextran-coated charcoal (DCC) method, the incidence of latent carcinoma was high. In 5 of 6 cases with latent carcinoma examined by immunohistochemistry, latent carcinomas showed expression of ER. Concerning Ki-67, proliferating cell nuclear antigen (PCNA) and p53 protein, there was no significant difference between the main and latent carcinomas, as well as with other clinicopathological factors.
Breast Cancer 1996 Dec 20
PMID:Multicentric Breast Carcinoma: Evaluation of Clinicopathological and Immunohistochemical Characteristics. 1109 56

The products of proliferating cell nuclear antigen (PCNA) and flap endonuclease (FEN1) genes are multifunctional proteins that are involved in DNA replication and damage repair. Yeast models suggest association of mutant forms of PCNA and FEN1 with genomic instability. In our study, we have determined the single nucleotide polymorphisms in human PCNA and FEN1 genes. We sequenced the coding region and adjacent noncoding region of both the PCNA and FEN1 genes in 120 alleles (60 individuals). In the PCNA gene, we detected 9 sequence variants with Hardy-Weinberg allele frequency ranging from 0.008 to 0.088. No polymorphism was detected in the FEN1 gene. The sequence variants in the PCNA gene included 7 intronic single nucleotide polymorphisms (SNP) and 2 synonymous exonic SNPs. All the intronic SNPs were located in introns 1 and 4, which contain several regulatory elements involved in the control of PCNA gene expression. Six of the 7 intronic SNPs showed complete linkage disequilibrium. We confirmed this allelic linkage disequilibrium by allele-specific PCR sequencing. We genotyped 117 additional individuals belonging to 3 population subgroups using the PCR-RFLP method. Finally, to see if the detected polymorphisms are associated with any cancer type, we genotyped cases with melanomas (37 cases), breast cancers (118 cases) and lung cancers (100 cases). We did not find statistical difference in frequency of polymorphism in any cancer type compared with healthy controls, although in breast cancer the frequency was low. Our results suggest that the coding regions of the PCNA and FEN1 genes are highly conserved when compared with other DNA repair genes. The potential of some of the detected intronic polymorphisms to effect regulation of the PCNA gene expression remains to be determined.
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PMID:Single nucleotide polymorphism analyses of the human proliferating cell nuclear antigen (pCNA) and flap endonuclease (FEN1) genes. 1109 18


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