| 1. |
- Agrup, Måns, et al.
(författare)
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C-erbB-2 overexpression and survival in early onset breast cancer
- 2000
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 63:1, s. 23-29
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Tidskriftsartikel (refereegranskat)abstract
- Young breast cancer patients have a decreased survival rate and it has been demonstrated that young age is an independent predictor of adverse prognosis. Overexpression of c-erbB-2 protein (also known as HER-2/neu) has been shown to be a prognostic indicator in breast cancer in general and especially among patients with axillary nodal metastases. The present study was initiated to determine the prognostic significance of c-erbB-2 protein overexpression in early onset breast cancer.A population consisting of 110 young breast cancer patients, ≤ 36-year-old at diagnosis, was analyzed with immunohistochemical staining for c-erbB-2 protein.Thirty patients (27%) were found to overexpress the c-erbB-2 protein. C-erbB-2 positivity was significantly associated with poor survival when all patients were included in the analysis (P = 0.002) and for patients with axillary nodal metastases (P = 0.0007). No such association was found for node-negative patients. Furthermore, the difference in prognosis in relation to c-erbB-2 among node-positive patients was maintained, when these were stratified in groups treated or not treated with adjuvant chemotherapy.The study indicates that overexpression of c-erbB-2 protein is a strong prognostic factor in young breast cancer patients with axillary nodal metastases. Moreover, the adverse prognosis associated with c-erbB-2 overexpression in node-positive patients was observed whether or not the patients had received adjuvant chemotherapy.
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| 2. |
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| 3. |
- Dabrosin, Charlotta, 1961-, et al.
(författare)
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Decreased secretion of Cathepsin D in breast cancer in vivo by tamoxifen : Mediated by the mannose-6-phosphate/IGF-II receptor?
- 2004
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 85:3, s. 229-238
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Tidskriftsartikel (refereegranskat)abstract
- The lysosomal protease Catliepsin D (Cath D) is associated with increased invasiveness and metastasis in breast cancer. Both estrogen and tamoxifen have been reported to increase Cath D, which seems to contradict the efficacy of tamoxifen as an adjuvant for estrogen dependent breast cancer. Cath D is bioactive in the extracellular space but very little is known about hormonal regulation of secreted Cath D in vivo. In this study we used microdialysis to sample the extracellular fluid in estrogen receptor positive MCF-7 tumors in nude mice. We show that tamoxifen in combination with estradiol decreased secreted Cath D compared with estradiol treatment only in solid tumors in situ. Cell culture of MCF-7 cells revealed that estradiol and tamoxifen increased intracellular proteolytic activity of Cath D in a similar fashion whereas secretion of Cath D was increased by estradiol and inhibited by tamoxifen. Immunofluorescence showed that estradiol located Cath D to the cell surface, while tamoxifen accumulated Cath D to dense lysosomes in perinuclear regions. Moreover, tamoxifen increased the intracellular transporter of Cath D, the mannose 6-phosphate/IGF-II receptor (M6P/IGF2R). In contrast, estradiol decreased the levels of this receptor. Thus, secretion of Cath D is hormone dependent and may be mediated by altered expression of the M6P/IGF2R. Our results highlight the importance of measurements of proteins in all compartments where they are biological active and show that microdialysis is a viable technique for sampling of Cath D in vivo.
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| 4. |
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| 5. |
- Dabrosin, Charlotta, 1961-
(författare)
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Increase of free insulin-like growth factor-1 in normal human breast in vivo late in the menstrual cycle
- 2003
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 80:2, s. 193-198
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Tidskriftsartikel (refereegranskat)abstract
- Prolonged exposure to endogenous and exogenous sex steroids increases the risk of breast cancer but the mechanisms are poorly understood. Increased levels of circulating insulin-like growth factor-1 (IGF-1) and low levels of IGF binding protein are associated with increased risk of breast cancer suggesting that IGF-1 has to be in its free form to be biologically active. Little is known about sex steroid regulation of IGF-1 locally in the breast. In this study microdialysis was used to determine the local levels of free IGF-1 in normal human breast tissue in healthy female volunteers during the menstrual cycle. The results showed that the extracellular levels of free IGF-1 locally in the breast were doubled in the luteal phase, when estradiol and progesterone levels were elevated, compared with the follicular phase. In plasma, free IGF-1 levels also exhibited a cyclic variation but to a less extent. The increased local levels of the tree form of IGF-1 may promote proliferation in the breast epithelium. This could be important in sex steroid dependent breast cancer development.
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| 6. |
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| 7. |
- Fernö, Mårten, et al.
(författare)
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Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels
- 2000
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217 .- 0167-6806. ; 59:1, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p = 0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p = 0.53 and p = 0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment. In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.
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| 8. |
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| 9. |
- Hellmen, Eva, et al.
(författare)
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Expression of different phenotypes in cell lines from canine mammary spindle-cell tumours and osteosarcomas indicating a pluripotent mammary stem cell origin
- 2000
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 61:3, s. 197-210
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Tidskriftsartikel (refereegranskat)abstract
- Mammary spindle-cell tumours and sarcomas seem to be restricted to dogs and humans. Two cell lines from spontaneous primary canine mammary spindle-cell tumours (CMT-U304 and CMT-U309) and two cell lines from spontaneous primary canine mammary osteosarcomas (CMT-U334 and CMT-U335) were established to study the mesenchymal phenotypes of mammary tumours in the female dog. The cells from the spindle-cell tumours expressed cytokeratin, vimentin and smooth muscle actin filaments. When these cells were inoculated subcutaneously into female and male nude mice they formed different types of mesenchymal tumours such as spindle-cell tumours, fibroma and rhabdomyoid tumours (n = 6/8). The cells from the osteosarcomas expressed vimentin filaments and also formed different types of mesenchymal tumours such as chondroid, rhabdomyoid, smooth muscle-like and spindle-cell tumours (n = 6/10). The cell lines CMT-U304, CMT-U309 and CMT-U335 had receptors for progesterone but none of the four cell lines had receptors for estrogen. All four cell lines and their corresponding primary tumours showed identical allelic patterns in microsatellite analysis. By in situ hybridization with genomic DNA we could verify that all formed tumours but one were of canine origin. Our results support the hypothesis that canine mammary tumours are derived from pluripotent stem cells.
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| 10. |
- Mikheev, A M, et al.
(författare)
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Frequent activation of CArG binding factor-A expression and binding in N-methyl-N-nitrosourea-induced rat mammary carcinomas
- 2004
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 88:1, s. 95-102
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Tidskriftsartikel (refereegranskat)abstract
- We previously identified a positive transcriptional element identical to human Ha-ras response element ( HRE) within the promoter of the rat Ha-ras gene. We further identified CArG binding factor A ( CBF-A), a member of heterogeneous nuclear ribonuclear protein ( hnRNP) gene family, as a trans-acting factor that binds the HRE sequence with high affinity in rat mammary carcinoma cells. To determine if activation of CBF-A plays a role in tumor development in vivo, we investigated CBF-A expression and binding activity in rat mammary tumors induced by N-methyl-N-nitrosourea. We found that -82% of tumors expressed CBFA at levels that were 3-20 fold higher than detected in normal mammary gland. Moreover, elevated CBF-A protein levels were invariably associated with increased binding activity to the HRE. CBF-A mRNA levels in tumors were on average elevated only two fold as compared to normal mammary gland, indicating that increased CBF-A protein levels in tumors resulted from both translational and/or post-translational regulation. The level of CBF-A expression in mammary tumors was independent of Ha-ras mutational status. Together, these findings indicated that deregulation of CBF-A contributes to mammary carcinogenesis via a mechanism that is distinct from its hnRNP functions in binding and post-transcriptional regulation of RNA.
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| 11. |
- Ryden, L, et al.
(författare)
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Tumor specific VEGF-A and VEGFR2/KDR protein are co-expressed in breast cancer
- 2003
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217 .- 0167-6806. ; 82:3, s. 147-154
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis is a prognostic indicator in primary breast cancer regulated by specific angiogenic factors and their receptors. Vascular endothelial growth factor-A (VEGF-A), so far considered the most important, acts through dimerization of the receptor VEGFR2/KDR within the receptor tyrosine kinase family of VEGF receptors. In order to study the interplay between VEGF-A and VEGFR2/KDR in breast cancer we evaluated their expression by immunohistochemistry in 102 breast cancers organized in a tumor tissue array system allowing semi-quantitative evaluation of cytoplasmatic staining intensity. In addition, VEGF-A(165) was analyzed by an enzyme immuno assay (ELISA) in protein extracts prepared from frozen tissue from 98 of 102 tumors included in the array. Cytoplasmatic staining of VEGF of varying intensity was observed in all samples and correlated with the ELISA results of VEGF content (p=0.007). Interestingly, VEGFR2/KDR expression correlated with VEGF expression using immunohistochemistry, indicating that VEGF and VEGFR2/KDR may be co-expressed in breast cancer. Furthermore, high levels of VEGF-A(165) in the protein extracts was associated with impaired short time survival but not long term survival whereas immunohistochemically assessed VEGF and VEGFR2/KDR were not significantly associated with survival. In summary, immunohistochemically based analysis of VEGF using a tumor tissue array system seems to be a useful method for VEGF quantification in breast cancer here validated using an ELISA based method. The tumor tissue array system enables opportunities of simultaneous analysis of markers engaged in angiogenesis justifying further studies using larger series of tumors.
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| 12. |
- Schüle, Jana, et al.
(författare)
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Down-regulation of the CD3-ζ chain in sentinel node biopsies from breast cancer patients
- 2002
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 74:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- Background. In several neoplastic diseases, immunosuppression has been shown to correlate with disease stage, progression, and outcome. As the prognosis for metastatic breast cancer is still pessimistic, additional strategies are being sought to improve survival. Local immunosuppression in sentinel node biopsies from 24 evaluable breast cancer patients was studied as a possible way of selecting patients for immunotherapy.Method. Sentinel node biopsy was performed in 24 out of 25 women operated on for primary breast cancer (one was not evaluable). Specimens were snap-frozen and double-stained for the zeta-chain of the T-cell receptor. The degree of down-regulation of the zeta-chain was evaluated in three different lymph-node areas: primary follicles, secondary follicles, and paracortex.Results. Down-regulation of varying degrees was noted in all 24 sentinel node biopsies. A high degree of down-regulation (more than 50% of T-cells not expressing zeta-chain) was seen in the primary follicles in six patients (25%), in the secondary follicles in 13 patients (72%), and in the paracortex in 19 patients (79%).Conclusion. Local down-regulation of an immune function parameter was seen in sentinel node biopsies from breast cancer patients. In addition to possible prognostic implications, the sentinel node might be an appropriate location for detecting early-stage immunological down-regulation, which might open a possibility of selecting patients who could benefit from immunotherapy.
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| 13. |
- Sundquist, Marie, et al.
(författare)
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A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer
- 2000
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 63:1, s. 11-15
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Tidskriftsartikel (refereegranskat)abstract
- Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2–11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.
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| 14. |
- Thomassen, M, et al.
(författare)
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Loss of heterozygosity at BRCA2 in a ductal carcinoma in situ and three invasive breast carcinomas in a family with a germline BRCA2 mutation
- 2004
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 87:3, s. 273-276
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Tidskriftsartikel (refereegranskat)abstract
- We have examined a family with a germline BRCA2 mutation in three cases of invasive breast cancer and one case of ductal carcinoma in situ ( DCIS). Loss of heterozygosity (LOH) has been demonstrated at the BRCA2 locus in all cases. This result may suggest that the germline mutation in BRCA2 is the initiating step of DCIS and support the theory that DCIS is a precursor of invasive breast carcinoma in hereditary breast cancer.
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| 15. |
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| 21. |
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| 22. |
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| 23. |
- Dong, CH, et al.
(författare)
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Second primary breast cancer in men
- 2001
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Ingår i: Breast cancer research and treatment. - 0167-6806. ; 66:2, s. 171-172
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 24. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Ito, Y, et al.
(författare)
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Activation of c-Src is inversely correlated with biological aggressiveness of breast carcinoma
- 2002
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 76:3, s. 261-267
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Tidskriftsartikel (refereegranskat)abstract
- In order to investigate whether c-Src is involved in carcinogenesis and progression of breast carcinoma, we examined the expression of activated c-Src in tissue sections from surgically resected human breast specimens. First, we confirmed the specificity of the antibody against activated c-Src (Clone 28) using six cell lines established from human breast carcinomas by western blotting. As expected, activated c-Src was detected as a 60 kDa band in all cell lines tested. Immunofluorescence analysis demonstrated that the activated c-Src was mainly observed in cytoplasms of these cells. Then, we designed an immunohistochemical study with 73 human breast carcinoma tissues. Glandular epithelial and myoepithelial cells in normal mammary glands adjacent to carcinoma nests and infiltrating stromal cells were negative for activated c-Src. In contrast, 37 of the 73 breast carcinoma tested (50.7%) were positive for activated c-Src, and this positive staining was inversely correlated with Ki-67 labeling index (p <0.0001), TNM stage (p <0.0001), tumor size (p < 0.0001), and histological grade (p = 0.0002). These results strongly suggest that the activation of c-Src would be related to the progression of breast carcinomas with low aggressiveness.
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| 29. |
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| 31. |
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| 33. |
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| 35. |
- Manjer, Jonas, et al.
(författare)
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Breast cancer incidence in relation to smoking cessation
- 2000
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 61:2, s. 121-129
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Tidskriftsartikel (refereegranskat)abstract
- High plasma levels of oestrogens are associated with increased breast cancer risk. If smoking, as has been suggested, have both a tumour initiating mutagenic effect and a protective anti-oestrogenic effect, one would assume that smokers who give up smoking have the highest incidence of breast cancer. This was evaluated in the follow-up of a cohort of 10,902 women of whom 4,359 were premenopausal. Record-linkage with official cancer registries yielded 416 incident cases during an average follow-up of 13.6 years. The adjusted relative risk in all ex-smokers was 1.31 (1.02-1.69), as compared to never smokers, and in premenopausal ex-smokers it was 1.57 (1.07-2.30). Breast cancer incidence in premenopausal ex-smokers was inversely related to time since cessation, (p for trend = 0.01), and was highest among the women who had given-up smoking less than 12 months before screening: 2.76 (1.55-4.91). There was no significant association between current smoking and breast cancer risk. We conclude that incidence of breast cancer in premenopausal women who have given up smoking is higher than it is in smokers and never smokers. To what extent this may be related to endocrine effects associated with smoking cessation remains to be evaluated.
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| 36. |
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| 37. |
- Ottesen, G L, et al.
(författare)
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Carcinoma in situ of the breast: correlation of histopathology to immunohistochemical markers and DNA ploidy
- 2000
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 60:3, s. 219-226
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Tidskriftsartikel (refereegranskat)abstract
- In a consecutive and unselected series of 178 cases of carcinoma in situ of the breast (CIS), comprising both ductal (DCIS) and lobular type (LCIS), and a series of 48 cases of invasive carcinoma (IC) with predominance of DCIS, the association between histopathology, immunohistochemical markers (ER, PgR, MIB-1, c-erbB-2, and p53), and DNA ploidy was investigated, in order to discriminate biologically different groups. In DCIS, significant correlation was shown between large nuclear size and comedonecrosis, both of which showed also strong association to DNA aneuploidy, high proliferation activity, low steroid receptor content, and overexpression of c-erbB-2 and p53 factors that may indicate an aggressive behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA diploid with low proliferation, and no cases showed overexpression of c-erbB-2 and p53. Heterogeneity with respect to the investigated parameters was also a frequent finding that may reflect a development complexity. In IC, comparison of the DCIS and the invasive component showed similar patterns. No significant differences were shown between DCIS without and with invasion. This may indicate that none of the investigated parameters on its own are essential for the event of invasion.
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| 38. |
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| 39. |
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| 40. |
- Stattin, Pär, et al.
(författare)
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Plasma leptin and breast cancer risk: a prospective study in northern Sweden
- 2004
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Ingår i: Breast Cancer Res Treat. - 0167-6806. ; 86:3, s. 191-196
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Tidskriftsartikel (refereegranskat)abstract
- Chronic burnout refers to a syndrome caused by chronic stress. Clinical observations indicate that chronic burnout is associated with impaired cognitive functioning. However, there have been no systematic studies of the cognitive performance in chronic burnout patients. We have evaluated general cognitive ability, memory, and attention in 67 female patients treated for chronic burnout. The patients and 15 healthy control subjects were tested with standardized tests of verbal and nonverbal cognitive ability (WAIS), verbal (Claeson-Dahl) and nonverbal (Rey complex figures) memory, and visual and auditory attention (IVA). Significant reductions in nonverbal memory and auditory and visual attention were found for the patient group. These results indicate that patients with chronic burnout have specific cognitive impairments, which should be emphasized in the evaluation of symptoms and treatment regimes in this disorder.
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| 41. |
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