| 1. |
- Borg, A., et al.
(författare)
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Association of int2/hst1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis
- 1991
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 63:1, s. 136-142
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Tidskriftsartikel (refereegranskat)abstract
- The human proto-oncogene INT2 (homologous to the mouse INT2 gene, implicated in proviral induced mammary carcinoma) has been mapped to chromosome llql3 and found to share band localisation with, among others, the HST1 proto-oncogene. Both genes are members of the fibroblast growth factor family. In the present study, coamplification (2-15 copies) of the INT2/HST1 genes was found in 27 (9%) of 311 invasive human breast carcinomas using slot blot and Southern blot analyses. Amplification was not correlated to tumour size, axillary lymph node status or stage of disease, neither to patient age nor menopausal status. However, 26 (96%) of the 27 amplified tumours were, often strongly, Oestrogen receptor positive compared to 65% of the unamplified cases (P = 0. 001). These findings are in sharp contrast to the strong correlations of HER-2/neu proto-oncogene amplification with advanced stage and steroid receptor negativity, previously observed in the same series of tumours. Patients with INT2/HSTI amplified breast cancer had a significantly shorter disease-free survival compared to those with unamplified genes (P = 0. 015, median follow up 45 months). This correlation was confined to node-negative patients and persisted in multivariate analysis. No significant correlation to survival from breast cancer was found. It is concluded that amplification of the 1 lql3 region in breast cancer occurs in a particular subset of aggressive tumours, quite different from that identified by HER-2/neu amplification. It still remains to be shown that the selection for amplified genes at llql3 is due to the activity of INT2, HSTl or yet another, still unidentified, neighbouring gene. However, the results are potentially of clinical value in separating a group of node-negative breast cancer for more intense treatment.
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| 2. |
- Fernö, Mårten, et al.
(författare)
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Cathepsin D, both a prognostic factor and a predictive factor for the effect of adjuvant tamoxifen in breast cancer. South Sweden Breast Cancer Group
- 1994
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Ingår i: European Journal of Cancer. - 1879-0852. ; 30a:14, s. 2042-2048
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Tidskriftsartikel (refereegranskat)abstract
- Cathepsin D is a lysosomal protease implicated in cancer metastasis. Its concentration in breast tumours has also been shown to be of prognostic importance, although to what extent this is subject to lymph node status, the use of adjuvant therapy and menopausal status has not been clearly evaluated. At a cut-off level of 45 pmol/mg protein (61% of the 623 samples were classified as high cathepsin D tumours; immunoradiometric assay), we found cathepsin D to be of prognostic importance only among breast cancer patients with lymph node-positive (N+) disease not treated with adjuvant tamoxifen. When the series was stratified according to cathepsin D content of their tumours, progesterone receptor (PgR) status and lymph node involvement, adjuvant tamoxifen was found to have a significant beneficial effect only among patients with N+ and PgR-positive breast cancer whose tumours had a high cathepsin D content.
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| 3. |
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| 4. |
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| 5. |
- Borg, A, et al.
(författare)
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HER-2/neu amplification predicts poor survival in node-positive breast cancer
- 1990
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Ingår i: Cancer Research. - 0008-5472. ; 50:14, s. 7-4332
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Tidskriftsartikel (refereegranskat)abstract
- HER-2/neu protooncogene amplification and protein expression were analyzed with slot blot and Western blot techniques, respectively, in more than 300 invasive primary breast tumors of all stages. Amplification (2- greater than 30 copies) was found in 17% of these tumors and high expression was seen in 19%. There was a striking coincidence between gene amplification and high expression. Tumors associated with many involved axillary lymph nodes or with Stage IV disease were more often HER-2/neu amplified or overexpressed. Furthermore, gene alteration was strongly correlated with the absence of steroid receptors and with larger tumor size. High expression without gene amplification was seen in a minor subset of tumors of less aggressive character. Neither amplification nor overexpression was correlated with disease outcome for patients with negative axillary lymph nodes. For node-positive patients, however, HER-2/neu amplification was a significant predictor of early relapse and death (median follow-up = 45 months), and a similar trend, although not significant, existed for high gene expression. Multivariate analyses indicated that HER-2/neu alterations were not independent predictors of patient outcome.
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| 6. |
- Borg, Åke, et al.
(författare)
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ERBB2 amplification in breast cancer with a high rate of proliferation
- 1991
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Ingår i: Oncogene. - 1476-5594. ; 6:1, s. 137-143
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Tidskriftsartikel (refereegranskat)abstract
- The ERBB2 proto-oncogene was studied in 539 invasive primary breast tumors and was found amplified (2- greater than 30 copies) in 19%. Amplification was correlated to most known risk factors, including; large tumor size, lymph node positivity and many tumor involved nodes, advanced stage, low patient age (less than 40 years), non-diploidy and hypertetraploidy, and most significantly (P less than 0.00001) to the absence of steroid receptors and to a high rate of proliferation (flow cytometric determined S phase fraction). ERBB2 amplification was strongly associated (P less than 0.0001) with early recurrence and death in breast cancer among node-positive patients. This connection did not, however, remain in multivariate analyses. No correlations to clinical outcome were seen among node-negative patients. Similarly, non-diploid, but not diploid, amplified tumors were particularly aggressive. Furthermore, ERBB2 amplification was associated with a high rate of proliferation and poor prognosis in steroid receptor positive, but not receptor negative tumors. In progesterone receptor positive breast cancer, amplification was an independent and with node status equally powerful (P less than 0.0001) predictor of poor survival. It is concluded that ERBB2 activity is related to an increased tumor growth rate but not directly to metastasizing ability. Its clinical relevance as a prognostic factor may be in selecting a high risk subgroup of breast cancer, in general considered as being of good prognosis.
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| 7. |
- Fernö, M., et al.
(författare)
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Estrogen and progesterone receptor analyses in more than 4000 human breast cancer samples : A study with special reference to age at diagnosis and stability of analyses
- 1990
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 29:2, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen (ER) and progesterone receptors (PgR) were measured in the same laboratory in more than 4000 breast cancer biopsy samples obtained from 15 different hospitals during ten years. ER was measured with isoelectric focusing and PgR with the dextran-coated charcoal method and Scatchard analysis. The distribution pattern for both ER and PgR was during this time period and for the different hospitals rather similar indicating a good stability of the analytical methods. ER concentration was positively correlated with patient age, with a higher percentage of positive samples and higher concentrations in patients ≥50 years of age compared with patients <50 years. PgR concentration increased with age for patients under 50 years, but a considerable reduction of PgR concentration and of the proportion of positive samples was seen in patients between 50 and 59 years of age. Above this age the PgR concentration again increased with increasing age. The PgR/ER ratio and the proportion of ER- PgR+ samples were higher in patients under 50 years compared to older patients. ER and PgR values decreased during tamoxifen treatment, during pregnancy and after preoperative radiotherapy. Wet weight, DNA and protein were compared as reference parameters for the expression of ER and PgR concentrations. Strong correlations were obtained suggesting that similar information can be obtained with either of these reference parameters.
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| 8. |
- Grepstad, J. K., et al.
(författare)
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As capping of MBE-grown compound semiconductors; novel opportunities to interface science and device fabrication
- 1994
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Ingår i: Physica Scripta. - 0031-8949. ; 1994:T54, s. 216-225
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Tidskriftsartikel (refereegranskat)abstract
- In situ condensation of an amorphous cap of the high vapour pressure element (i.e. As, Sb) has been found to provide effective protection of molecular beam epitaxy grown compound semiconductor surfaces against ambient contamination. Most work reported so far relates to arsenic-capped AlGaAs. Detailed investigation with surface sensitive structural (RHEED, LEED) and chemical (XPS) probes confirms that the protective cap is conveniently removed by annealing in ultrahigh vaccum environments at a temperature in excess of similar 350 °C. Clean AlxGa1-xAs(001) surfaces with different atomic reconstructions and corresponding (Al)Ga: As composition ratios are now routinely prepared by this technique, and thus offers an ideal testing ground for compound semiconductor surface and interface research. Reconstruction-dependent reactivity at metal/GaAs(001) interfaces is demonstrated, using surface sensitive synchrotron radiation photoelectron spectroscopy. Exploiting the protection offered by the As (Sb) cap for device fabrication purposes (e.g. in selective area epitaxy), demands a suitable method of pattern definition in the amorphous arsenic layer. The cap is shown to be chemically stable versus exposure to standard photolithographic processing chemicals, including photoresist, developer, and acetone (the photoresist solvent). However, the temperature required for thermal decapping is grossly inappropriate for photoresist curing. A novel technique of reactive decapping in a beam of hydrogen radicals (H‒) is shown to be effective at room temperature. This innovation makes pattern definition in the As cap compatible with standard photolithography, and test structures with similar 5 μm linewidth is demonstrated. Scanning electron micrographs unveil the presence of arsenic cap residues along the photoresist mask edges. Moreover, trace amounts of surface gallium oxide and carbon impurities were found with core-level photoelectron spectroscopy. The technique thus needs further refinement, before being useful in fabrication of compound semiconductor device structures.
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| 9. |
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| 10. |
- Olsson, H., et al.
(författare)
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Early oral contraceptive use and premenopausal breast cancer--a review of studies performed in southern Sweden.
- 1991
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Ingår i: Cancer Detection and Prevention. - 0361-090X. ; 15:4, s. 265-271
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Tidskriftsartikel (refereegranskat)abstract
- In southern Sweden, extensive oral contraceptive use (OC use) among young women was a reality during the 1960s, thus making our region especially suited for studies investigating the hypothesis that early OC use is associated with the development of premenopausal breast cancer after a possible latency time between the exposure and the disease. The results of this study revealed that the risk of developing premenopausal breast cancer in women, who during the 1960s used the pill as teenagers, is five times greater than nonusers. The risk for early users is further modified by the duration of use at an early age, implying a dose-response relationship. Later use of OCs is not associated with an increased risk for the disease. Women with breast cancer, who at an early age have used the pill, have larger breast tumors, lower estrogen receptor concentrations of their primary tumor, and a worse prognosis compared with later and nonusers with breast cancer. The incidence of breast cancer in Sweden rapidly increased in women 25 to 40 years of age between 1970 and 1984. Conventional risk factors or a change in diagnostic activities of breast cancer cannot explain the increase in incidence which could be due to the OC exposure. Studies on the risk with modern OCs must wait another 20 years because of a too short latency time.
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| 11. |
- Sigurdsson, H, et al.
(författare)
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Flow cytometry in primary breast cancer: improving the prognostic value of the fraction of cells in the S-phase by optimal categorisation of cut-off levels
- 1990
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Ingår i: British Journal of Cancer. - 1532-1827. ; 62:5, s. 786-790
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Tidskriftsartikel (refereegranskat)abstract
- The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level.
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| 12. |
- Sigurdsson, H, et al.
(författare)
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Indicators of prognosis in node-negative breast cancer
- 1990
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 322:15, s. 1045-1053
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Tidskriftsartikel (refereegranskat)abstract
- Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided.
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| 13. |
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