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Sökning: WFRF:(Warnberg Fredrik)

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1.
  • Strell, Carina, et al. (författare)
  • Impact of Epithelial-Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 1460-2105 .- 0027-8874. ; 111:9, s. 983-995
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A better definition of biomarkers and biological processes related to local recurrence and disease progression is highly warranted for ductal breast carcinoma in situ (DCIS). Stromal-epithelial interactions are likely of major importance for the biological, clinical, and pathological distinctions between high- and low-risk DCIS cases.METHODS: Stromal platelet derived growth factor receptor (PDGFR) was immunohistochemically assessed in two DCIS patient cohorts (n = 458 and n = 80). Cox proportional hazards models were used to calculate the hazard ratios of recurrence. The molecular mechanisms regulating stromal PDGFR expression were investigated in experimental in vitro co-culture systems of DCIS cells and fibroblasts and analyzed using immunoblot and quantitative real-time PCR. Knock-out of JAG1 in DCIS cells and NOTCH2 in fibroblasts was obtained through CRISPR/Cas9. Experimental data were validated by mammary fat pad injection of DCIS and DCIS-JAG1 knock-out cells (10 mice per group). All statistical tests were two-sided.RESULTS: PDGFRα(low)/PDGFRβ(high) fibroblasts were associated with increased risk for recurrence in DCIS (univariate hazard ratio = 1.59, 95% confidence interval [CI] = 1.02 to 2.46; P = .04 Wald test; multivariable hazard ratio = 1.78, 95% CI = 1.07 to 2.97; P = .03). Tissue culture and mouse model studies indicated that this fibroblast phenotype is induced by DCIS cells in a cell contact-dependent manner. Epithelial Jagged1 and fibroblast Notch2 were identified through loss-of-function studies as key juxtacrine signaling components driving the formation of the poor prognosis-associated fibroblast phenotype.CONCLUSIONS: A PDGFRα(low)/PDGFRβ(high) fibroblast subset was identified as a marker for high-risk DCIS. The Jagged-1/Notch2/PDGFR stroma-epithelial pathway was described as a novel signaling mechanism regulating this poor prognosis-associated fibroblast subset. In general terms, the study highlights epithelial-stromal crosstalk in DCIS and contributes to ongoing efforts to define clinically relevant fibroblast subsets and their etiology.
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2.
  • Unukovych, Dmytro, et al. (författare)
  • Breast reconstruction patterns from a Swedish nation-wide survey
  • 2020
  • Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 46:10 Pt A, s. 1867-1873
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The overall aim of the Swedish Breast Reconstruction Outcome Study was to investigate national long-term outcomes after mastectomy with or without breast reconstruction. The current report evaluates breast reconstruction (BR) patterns in Sweden over time. Materials and methods: This is a cross-sectional, registry-based study where all women operated with mastectomy 2000, 2005, 2010 were identified (N = 5853). Geographical differences in type of BR were investigated using heatmaps. Distribution of continuous variables were compared using the Mann-Whitney U test, categorical variables were compared using the chi-square test. Results: Mean age at survey was 69 years (SD=±11.4) and response rate was 50%, responders were on average six years younger than the non-responders and had a more favourable tumor stage (both p < 0.01). Of the 2904 responders, 31% (895/2904) had received a BR: implant-based in 58% (516/895)autologous in 31% (281/895). BR was immediate in 20% (176/895) and delayed in 80% (719/895) women. Women with BR were on average one year older, more often had a normal BMI, reported to be married or had a partner, had a higher educational level and a higher annual income when compared to those without BR (all p < 0.001). The independent factors of not receiving BR were older age and given radiotherapy. Conclusions: To our knowledge, this is the first national long-term follow-up study on women undergoing mastectomy with and without BR. Around 30% of the survey responders have had a BR with a significant geographical variation highlighting the importance of information, availability and standardisation of indications for BR.
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3.
  • Wadsten, Charlotta, et al. (författare)
  • A validation of DCIS registration in a population-based breast cancer quality register and a study of treatment and prognosis for DCIS during 20 years : Two decades of DCIS in Sweden
  • 2016
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:11, s. 1338-1343
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Sweden has a long history of population-based cancer registration. The aim of our study was to assess the validity of DCIS registration in a regional Breast Cancer Quality Register (BCQR) and to analyze trends in incidence, treatment and outcome of DCIS, over a 20-year period.Material and methods: All patients with a diagnosis of primary DCIS reported in the BCQR of the Uppsala-orebro healthcare region in Sweden 1992-2012 were included. Three hundred women were randomly selected and their medical records were compared to register data. The study period was divided into four time periods.Results: A total of 2952 women were registered with a DCIS diagnosis. In the final validation cohort of 295 patients, 23 were found to have either recurrent DCIS or invasive breast cancer and eight had LCIS. The completeness and validity of key variables were 91-99%. Twenty of 31 local recurrences were registered (65%).The proportion of DCIS to all breast cancers was 9.5%. Tumor size increased over time. The frequency of mastectomy increased from 23.0% to 39.0%. The proportion of patients receiving radiotherapy after breast conserving surgery increased from 30.1% to 67.6%. The reported local recurrence rate was 9.7% after 10 years. Reported recurrences after BCS and mastectomy were 12.0 and 7.0%, respectively. The recurrence rate did not differ between women undergoing BCS with or without radiotherapy.Conclusion: Only 89.5% of reported DCIS was a primary pure DCIS. The completeness of primary treatment and tumor data was high. The proportion of reported local recurrences was disappointingly low, 65%. The proportion of DCIS was stable over time with a trend towards more intensified treatment. The reported recurrence rate was low independent of treatment and can reflect adequate patient selection, but also over treatment. Our results address the necessity to validate register data on a regular basis.
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5.
  • Borgquist, Signe, et al. (författare)
  • The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study
  • 2015
  • Ingår i: BMC Cancer. - : BioMed Central (BMC). - 1471-2407 .- 1471-2407. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: HER2 is a well-established prognostic and predictive factor in invasive breast cancer. The role of HER2 in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that HER2 is mainly related to in situ recurrences. Our aim was to study HER2 as a prognostic factor in a large population based cohort of DCIS with long-term follow-up. Methods: All 458 patients diagnosed with a primary DCIS 1986-2004 in two Swedish counties were included. Silver-enhanced in situ hybridisation (SISH) was used for detection of HER2 gene amplification and protein expression was assessed by immunohistochemistry (IHC) in tissue microarrays. HER2 positivity was defined as amplified HER2 gene and/or HER2 3+ by IHC. HER2 status in relation to new ipsilateral events (IBE) and Invasive Breast Cancer Recurrences, local or distant (IBCR) was assessed by Kaplan-Meier survival analyses and Cox proportional hazards regression models. Results: Primary DCIS was screening-detected in 75.5 % of cases. Breast conserving surgery (BCS) was performed in 78.6 % of whom 44.0 % received postoperative radiotherapy. No patients received adjuvant endocrine-or chemotherapy. The majority of DCIS could be HER2 classified (N = 420 (91.7 %)); 132 HER2 positive (31 %) and 288 HER2 negative (69 %)). HER2 positivity was related to large tumor size (P = 0.002), high grade (P < 0.001) and ER-and PR negativity (P < 0.001 for both). During follow-up (mean 184 months), 106 IBCRs and 105 IBEs were identified among all 458 cases corresponding to 54 in situ and 51 invasive recurrences. Eighteen women died from breast cancer and another 114 had died from other causes. The risk of IBCR was statistically significantly lower subsequent to a HER2 positive DCIS compared to a HER2 negative DCIS, (Log-Rank P = 0.03, (HR) 0.60 (95 % CI 0.38-0.94)). Remarkably, the curves did not separate until after 10 years. In ER-stratified analyses, HER2 positive DCIS was associated with lower risk of IBCR among women with ER negative DCIS (Log-Rank P = 0.003), but not for women with ER positive DCIS. Conclusions: Improved prognostic tools for DCIS patients are warranted to tailor adjuvant therapy. Here, we demonstrate that HER2 positive disease in the primary DCIS is associated with lower risk of recurrent invasive breast cancer.
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6.
  • Karakatsanis, Andreas, et al. (författare)
  • The Nordic SentiMag trial : a comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc(99) and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies.
  • 2016
  • Ingår i: Breast Cancer Research and Treatment. - New York : Springer-Verlag New York. - 0167-6806 .- 1573-7217. ; 157:2, s. 281-294
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study is to compare the efficacy of SPIO as a tracer in sentinel node biopsy (SNB) in breast cancer with Tc and patent blue in a multicentre prospective study and perform a meta-analysis of all published studies. It also aims to follow skin discoloration after SPIO injection and describe when and how it resolves. Totally 206 patients with early breast cancer were recruited. Tc and patent blue were administered in standard fashion. Patients were injected with SPIO (Sienna+) preoperatively. SNB was performed and detection rates were recorded for both methods. Skin discoloration was followed and documented postoperatively. Data extraction and subsequent meta-analysis of all previous studies were also performed. SN detection rates were similar between standard technique succeeded and SPIO both per patient (97.1 vs. 97.6 %, p = 0.76) as well as per node (91.3 vs. 93.3 %, p = 0.34), something which was not affected by the presence of malignancy. Concordance rates were also consistently high (98.0 % per patient and 95.9 % per node). Discoloring was present in 35.5 % of patients postoperatively, almost exclusively in breast conservation. It fades slowly and is still detectable in 8.6 % of patients after 15 months. Meta-analysis depicted similar detection rates (p = 0.71) and concordance rates (p = 0.82) per patient. However, it seems that SPIO is characterized by higher nodal retrieval (p < 0.001). SPIO is an effective method for the detection of SN in patients with breast cancer. It is comparable to the standard technique and seems to simplify logistics. Potential skin discoloration is something of consideration in patients planned for breast conservation.
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7.
  • Karlsson, E., et al. (författare)
  • Clonal alteration of breast cancer receptors between primary ductal carcinoma in situ (DCIS) and corresponding local events
  • 2014
  • Ingår i: European Journal of Cancer. - : Elsevier. - 1879-0852 .- 0959-8049. ; 50:3, s. 517-524
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Emerging data propose biomarker alteration due to clonal selection between the primary invasive breast cancer and corresponding metastases. In addition, impact on survival has been demonstrated. The present study investigates the relationship between the oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) between primary ductal carcinoma in situ (DCIS) and intra-individually matched ipsilateral event. Materials and methods: The cohort includes 1504 patients, diagnosed with a primary DCIS between 1986 and 2004. Of the 274 patients who developed a local relapse, 135 developed a new in situ carcinoma and 139 an invasive cancer up to 31st December 2011. ER and PR were identified by immunohistochemistry (IHC) and HER2 by silver-enhanced in situ hybridisation (SISH) as well as IHC. Results: ER (n = 112), PR (n = 113) and HER2 (n = 114) status from both the primary DCIS and the corresponding relapse were assessed and were demonstrated to be discordant in 15.1%, 29.2% and 10.5% respectively. The receptor conversion was both from negative to positive and from positive to negative with no general pattern being seen in spite of sub-dividing into in situ relapse and invasive relapse. However, primary DCIS was HER2 positive in 40.3% whereas in situ and invasive relapses were HER2 positive in 42.9% and 34.5% respectively. Conclusions: Receptor conversion for ER, PR and HER2 status occurred between primary DCIS and corresponding local relapse in 10-30%. This study could not confirm that HER2 overexpression in primary DCIS had any impact on tumour progression to invasive cancer which has been proposed. (C) 2013 Elsevier Ltd. All rights reserved.
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8.
  • Norenstedt, Sophie, et al. (författare)
  • Breast cancer associated with primary hyperparathyroidism : a nested case control study
  • 2011
  • Ingår i: Clinical Epidemiology. - 1179-1349 .- 1179-1349. ; 3, s. 103-106
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Primary hyperparathyroidism (pHPT) is associated with an increased risk of developing breast cancer, but little is known about the underlying factors. The aim of this study was to compare women with a history of pHPT and a reference population in terms of standard factors predictive of prognosis and response to therapy for breast cancer. METHODS: We analyzed data collected from the National Swedish Cancer Register and from two regional oncologic center registries. Seventy-one women with breast cancer and a history of parathyroid adenomectomy were compared with 338 matched controls with breast cancer only. Tumor size, stage, hormone receptor status, lymph node status, cause of death, and cumulative survival were analyzed. RESULTS: The mean age was 69 ± 11 years (95% confidence interval [CI]: 68-70) in both groups and the mean time interval between the parathyroid surgery and breast cancer diagnosis was 91 ± 68 months (95% CI: 72-111). There were no differences between the two groups regarding size, stage, lymph node metastases, or survival, but none of the cases with a history of pHPT were found in Stage III or IV. CONCLUSION: In conclusion, factors predictive of prognosis and response to therapy in women with a history of pHPT and breast cancer are similar to those in breast cancer patients without pHPT.
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9.
  • Wadsten, Charlotta, et al. (författare)
  • Risk of death from breast cancer after treatment for ductal carcinoma in situ
  • 2017
  • Ingår i: British Journal of Surgery. - : WILEY. - 0007-1323 .- 1365-2168. ; 104:11, s. 1506-1513
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Studies to date have failed to demonstrate any survival benefit from preventing local recurrence after treatment for ductal breast carcinoma in situ (DCIS). Patient- and tumour-related risk factors for death from breast cancer in women with a primary DCIS were analysed here in a large case-control study.Methods A nested case-control study was conducted in a population-based cohort of women with primary DCIS between 1992 and 2012. Women who later died from breast cancer were identified. Four controls per case were selected randomly by incidence density sampling. Medical records and pathology reports were retrieved. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 per cent confidence intervals for risk of death from breast cancer.Results From a cohort of 6964 women, 96 who died from breast cancer were identified and these were compared with a group of 318 controls. Tumour size over 25mm or multifocal DCIS (OR 255, 95 per cent c.i. 153 to 425), a positive or uncertain margin status (OR 391, 159 to 961) and detection outside the screening programme (OR 212, 116 to 386) increased the risk of death from breast cancer. The risks were not affected by age or type of treatment. In the multivariable analysis, tumour size (OR 195, 106 to 367) and margin status (OR 269, 115 to 711) remained significant.Conclusion In the present study, large tumour size and positive or uncertain margin status were associated with a higher risk of death from breast cancer after treatment for primary DCIS. More extensive treatment was not associated with lower risk, which may be due to confounding by indication, or indicate that some DCIS has an inherent potential for metastatic spread. Rare, but worse for large tumours and uncertain margins.
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10.
  • Warnberg, F., et al. (författare)
  • Quality aspects of the tissue microarray technique in a population-based cohort with ductal carcinoma in situ of the breast
  • 2008
  • Ingår i: Histopathology. - : Wiley-Blackwell. - 0309-0167 .- 1365-2559. ; 53:6, s. 642-649
  • Tidskriftsartikel (refereegranskat)abstract
    • Tissue microarray (TMA) is an efficient technique for analysis of molecular markers. Prospectively collected samples have been reported to give excellent concordance between TMA data and corresponding whole-sections. The aim was to evaluate the usefulness of TMA in a population-based cohort of 213 women with ductal carcinoma in situ of the breast (DCIS). We studied immunohistochemical HER2, oestrogen (ER) and progesterone (PR) receptor status. The prognostic impact was similar for all markers comparing whole sections and TMAs. The proportion of positive tumours was similar regarding HER2 and ER, whereas PR tumours were more frequently positive in the TMAs (P = 0.007). The concordance was 80% (kappa value 0.63) between original sections and TMAs. The proportion of successfully analysed tumours was 70%. Smaller tumours had a lower ratio (P < 0.0001) and a larger proportion of mismatched results (P = 0.05). Retrospective analyses of tumours from cohorts with long-term follow-up are indispensable. We have shown that the TMA technique is a useful tool for high-throughput analysis of DCIS. However, our study has pinpointed some technical hazards within a population-based cohort, including many small lesions and the poor condition of some donor blocks. Mismatched results may be due to tumour heterogeneity.
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