| 1. |
- Tzikas, Anna-Karin, 1977, et al.
(author)
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A comparison between young and old patients with triple-negative breast cancer: biology, survival and metastatic patterns
- 2020
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 182, s. 643-654
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Journal article (peer-reviewed)abstract
- Purpose To determine the biology, recurrence rate, metastatic patterns and survival times in primary triple-negative breast cancer (TNBC) with focus on the comparison between younger and elderly patients. Methods Patients with primary TNBC stage I-IV diagnosed from 2007 to 2015 were identified and information on tumor biology, stage, treatment, recurrences and death recorded. Results A total of 524 patients, median age 60 years (range 24-94) with a median follow-up of 55 months (range 0-129) were identified. Stage was similar in younger (< 40 years) (n = 58) and older (> 74 years) (n = 96) patients (p = 0.37). A statistically significant difference was found concerning histopathologic grade (p = 0.006) and Ki67 (median 80% versus 70%;p = 0.002) but not for LVI (p = 0.9) with more aggressive tumors among younger patients. Adjuvant/neoadjuvant chemotherapy was more frequently given to younger compared with older patients (96% versus 12%;p = 0.0005). Only brain (p = 0.016) and liver (p = 0.047) metastases were more often registered among younger patients while other locations were similar. Shorter survival times, recurrence-free survival (RFS), distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS) were found in the older group, although not after adjusting for adjuvant/neoadjuvant chemotherapy. Most deaths (68%) in the older group were caused by TNBC. When comparing patients > 75 years (n = 92) with <= 75 years (n = 432), a worse outcome among older was also observed: RFS (p = 0.00012), DDFS (p = 0.00041), BCSS (p < 0.0001) and survival following distant metastasis (p = 0.0064) Conclusions Primary TNBC in younger patients is more often of poor differentiation grade and highly proliferative compared with older patients. The majority of older patients still have grade III tumors with a Ki67 > 60% and outcome is poor. Few older patients in our study were treated with chemotherapy both in adjuvant and palliative setting, underlining the need for more prospective trials and treatment options suitable for this patient population.
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| 2. |
- Alfonzo, Emilia, et al.
(author)
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Effect of Fee on Cervical Cancer Screening Attendance-ScreenFee, a Swedish Population-Based Randomised Trial
- 2016
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Journal article (peer-reviewed)abstract
- Background Attendance in the cervical cancer screening programme is one of the most important factors to lower the risk of contracting the disease. Attendance rates are often low in areas with low socioeconomic status. Charging a fee for screening might possibly decrease attendance in this population. Screening programme coverage is low in low socio-economic status areas in Gothenburg, Sweden, but has increased slightly after multiple interventions in recent years. For many years, women in the region have paid a fee for screening. We studied the effect of abolishing this fee in a trial emanating from the regular cervical cancer screening programme. Individually randomised controlled trial. All 3 124 women in three low-resource areas in Gothenburg, due for screening during the study period, were randomised to receive an offer of a free test or the standard invitation stating the regular fee of 100 SEK (approximate to 11 (sic)). The study was conducted during the first six months of 2013. Attendance was defined as a registered Pap smear within 90 days from the date the invitation was sent out. Attendance did not differ significantly between women who were charged and those offered free screening (RR 0.93; CI 0.85-1.02). No differences were found within the districts or as an effect of age, attendance after the most recent previous invitation or previous experience of smear taking. Abolishment of a modest screening fee in socially disadvantaged urban districts with low coverage, after previous multiple systematic interventions, does not increase attendance in the short term. Other interventions might be more important for increasing attendance in low socio-economic status areas.
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| 3. |
- Bengtsson, Albin, 1985, et al.
(author)
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Consistency in patient-reported outcomes after total hip replacement: A 6-year registry follow-up of 15,755 patients
- 2017
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 88:5, s. 484-489
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Journal article (peer-reviewed)abstract
- Purpose - The primary objective in this study was to describe the patient-reported outcome measures (PROMs) of total hip replacement (THR) patients 6 years after index surgery. Second, we sought to analyze how the preoperative, 1- and 6-year outcomes were associated. Patients and methods - By assessing the Swedish Hip Arthroplasty Register (SHAR), 15,755 patients with complete follow-up were included in the study group. 1-year and 6-year response rates were 93% and 87%. PROMs used by the SHAR include the EQ-5D instrument, and 2 modified visual analogue scales, 1 for pain and 1 for satisfaction. We used a multivariable linear regression model to examine the relationship between preoperative, 1-year, and 6-year outcome. Results - On average, patient-reported outcomes 6 years after THR were satisfactory. Though there was some deterioration in all mean 6-year PROMs, the patient-reported outcome after 6 years strongly resembled that of the 1-year results. The 1-year follow-up was the strongest factor associated with the 6-year results. Interpretation - There is little deterioration in patient-reported outcomes 6 years after THR compared with the 1-year results. Although the 1-year follow-up was the strongest predictor of the 6-year results it could not alone explain the results, thus supporting the utility of the 6-year follow-up in THR patients.
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| 4. |
- Biermann, Jana, et al.
(author)
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A novel 18-marker panel predicting clinical outcome in breast cancer
- 2017
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In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 26:11, s. 1619-28
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Journal article (peer-reviewed)abstract
- Gene expression profiling has made considerable contributions to our understanding of cancer biology and clinical care. This study describes a novel gene expression signature for breast cancer-specific survival that was validated using external datasets. Gene expression signatures for invasive breast carcinomas (mainly Luminal B subtype) corresponding to 136 patients were analysed using Cox regression and the effect of each gene on disease-specific survival (DSS) was estimated. Iterative Bayesian Model Averaging was applied on multivariable Cox regression models resulting in an 18-marker panel, which was validated using three external validation datasets. The 18 genes were analysed for common pathways and functions using the Ingenuity Pathway Analysis software. This study complied with the REMARK criteria. The 18-gene multivariable model showed a high predictive power for DSS in the training and validation cohort and a clear stratification between high- and low-risk patients. The differentially expressed genes were predominantly involved in biological processes such as cell cycle, DNA replication, recombination, and repair. Furthermore, the majority of the 18 genes were found to play a pivotal role in cancer. Our findings demonstrated that the 18 molecular markers were strong predictors of breast cancer-specific mortality. The stable time-dependent area under the ROC curve function (AUC(t)) and high C-indices in the training and validation cohorts were further improved by fitting a combined model consisting of the 18-marker panel and established clinical markers. Our work supports the applicability of this 18-marker panel to improve clinical outcome prediction for breast cancer patients.
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| 5. |
- Biermann, Jana, et al.
(author)
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Clonal relatedness in tumour pairs of breast cancer patients.
- 2018
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In: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 20:1
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Journal article (peer-reviewed)abstract
- Molecular classification of tumour clonality is currently not evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. There is no consensus about which type of data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours.Thirty-seven invasive breast tumour pairs were stratified according to laterality and time interval between the diagnoses of the two tumours. In a multi-omics approach, tumour clonality was analysed by integrating clinical characteristics (n=37), DNA copy number (n=37), DNA methylation (n=8), gene expression microarray (n=7), RNA sequencing (n=3), and SNP genotyping data (n=3). Different statistical methods, e.g. the diagnostic similarity index (SI), were used to classify the tumours as clonally related recurrences or independent primary tumours.The SI and hierarchical clustering showed similar tendencies and the highest concordance with the other methods. Concordant evidence for tumour clonality was found in 46% (17/37) of patients. Notably, no association was found between the current clinical guidelines and molecular tumour features.A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. Guidelines need to be defined with exact thresholds to standardise clonality testing in a routine diagnostic setting.
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| 6. |
- Biermann, Jana, et al.
(author)
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Radiation-induced genomic instability in breast carcinomas of the Swedish haemangioma cohort.
- 2019
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In: Genes, chromosomes & cancer. - : Wiley. - 1098-2264 .- 1045-2257. ; 58:9, s. 627-35
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Journal article (peer-reviewed)abstract
- Radiation-induced genomic instability (GI) is hypothesized to persist after exposure and ultimately promote carcinogenesis. Based on the absorbed dose to the breast, an increased risk of developing breast cancer was shown in the Swedish haemangioma cohort that was treated with radium-226 for skin haemangioma as infants. Here, we screened 31 primary breast carcinomas for genetic alterations using the OncoScan CNV Plus Assay to assess GI and chromothripsis-like patterns associated with the absorbed dose to the breast. Higher absorbed doses were associated with increased numbers of copy number alterations (CNAs) in the tumour genome and thus a more unstable genome. Hence, the observed dose-dependent GI in the tumour genome is a measurable manifestation of the long-term effects of irradiation. We developed a highly predictive Cox regression model for overall survival based on the interaction between absorbed dose and GI. The Swedish haemangioma cohort is a valuable cohort to investigate the biological relationship between absorbed dose and GI in irradiated humans. This work gives a biological basis for improved risk assessment to minimize carcinogenesis as a secondary disease after radiation therapy. This article is protected by copyright. All rights reserved.
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| 7. |
- Biermann, Jana, et al.
(author)
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Tumour clonality in paired invasive breast carcinomas
- 2019
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In: Cancer Research. - 0008-5472.
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Conference paper (other academic/artistic)abstract
- Background: Multiple invasive breast tumours may represent either independent primary tumours or clonal recurrences of the first tumour, where the same progenitor cell gives rise to all of the detected tumours. Consequently, the driver events for the progenitor cell need to have been identical in early tumour development. Molecular classification of tumour clonality is not currently evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. Furthermore, there is no consensus about which type of biological data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours. Methods: Thirty-seven invasive breast tumour pairs were stratified by laterality (bilateral vs. ipsilateral) and the time interval between the diagnoses of the first and second tumours (synchronous vs. metachronous). Both tumours from the same patient were analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), distance measure, shared segment analysis etc., were used to classify the tumours from the same patient as clonally related recurrences or independent primary tumours. Results: The SI applied on DNA copy numbers derived from aCGH (array comparative genomic hybridization) data was determined as the strongest indicator of clonal relatedness as it showed the highest concordance with all other methods. The distance measure was the most conservative method and the shared segment analysis most liberal. Concordant evidence for tumour clonality was found in 46% (17/37) of the patients. Notably, no significant association was found between the clinical characteristics and molecular tumour features. Conclusions: A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. In cases of extremely similar or different tumour pairs, the results showed consistency regardless of the method used. The SI can be easily integrated into clinical routine using FFPE samples to obtain copy number data. However, clinical guidelines with exact thresholds need to be defined to standardize clonality testing in a routine diagnostic setting.
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| 8. |
- Bülow, Erik, et al.
(author)
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Are the First or the Second Hips of Staged Bilateral THAs More Similar to Unilateral Procedures? A Study from the Swedish Hip Arthroplasty Register
- 2020
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In: Clinical Orthopaedics and Related Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-921X .- 1528-1132. ; 478:6, s. 1262-1270
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Journal article (peer-reviewed)abstract
- Background Bilateral THAs performed in the same patient should not be considered independent observations, neither biologically nor statistically. As a result, when surgical results are reviewed, it is common to analyze only the first of the two hips, assuming that the first, and not the second hip of a staged bilateral THA, better resembles unilateral THAs. This assumption has not been empirically justified. Question/purposes (1) In patients with staged bilateral THA, is the first or second hip more similar to a unilateral THA in terms of age at surgery, presence of any preoperative Charlson comorbidity, and risk of postoperative reoperation? (2) Should the date of a first or second hip surgery of a staged bilateral THA be used as a starting point for patient survival to better resemble patients with unilateral THA? Methods We identified 68,357 THAs due to osteoarthritis in 63,613 patients from the Swedish Hip Arthroplasty Register (SHAR) in 1999-2015. Of those THAs, 14,780 concerned the first hip of a staged bilateral procedure performed between 1999 and 2004; 28,542 were unilaterals from 2004 to 2008, and 25,035 concerned the second hip of a staged bilateral procedure performed 2008 to 2015. We excluded patients who underwent one-stage bilateral THAs. We used different inclusion periods to distinguish unilateral procedures from the first and second hips from staged bilateral procedures because sufficiently long set-up and follow-up periods were needed before and after each period to identify possible contralateral THAs. This introduced potential period confounding, meaning that possible group differences might not be distinguished from unrelated outcome differences over time. We investigated if such time trends existed. It did not for age and reoperation rates, but it did for comorbidity and patient survival. Our primary study endpoint was whether patients with unilateral THAs were more similar to patients with a first hip of a staged bilateral THA, or to patients with their second hip operated. We used Student's t-test to compare mean age at surgery. The proportion of patients with at least one presurgery Charlson comorbidity were compared by 95% bootstrap confidence intervals, after subtracting the yearly time-trend to avoid period confounding. Postoperative risks of reoperation were compared by log-rank tests of Kaplan-Meier curves and by comparing 5-year reoperation rates by pair-wise 95% CIs. Our secondary study endpoint was to compare patient survival for patients with a unilateral THA, a first hip of a staged bilateral THA, or a second hip of a staged bilateral THA. We evaluated this by relative 5-year survival, comparing patients of each group with the general Swedish population of the same age, sex, and year of birth. This way, possible survival differences would be less likely explained by period confounding. Results Patients undergoing unilateral THA were older than those undergoing a first hip of a staged bilateral THA (70 +/- 10 versus 66 +/- 9 years, mean difference of 4; p < .001), but they were not different from patients undergoing the second hip of a staged bilateral THA (70 +/- 9 years, mean difference of 0; p = 0.74). The period-adjusted proportion of patients with unilateral THA and presurgery comorbidity (Charlson index > 0) was 20% (95% CI: 19.8-20.7). This was no different from patients with a second hip from a staged bilateral THA (20%; 19.7-20.6), but higher compared to patients with a first hip of a staged bilateral THA (15%; 14.5-15.4). For reoperation rates, the log-rank tests showed no difference between unilateral THAs and the second hips of staged bilateral THAs (). Such difference was found for unilaterals compared with the first hips of staged bilateral THAs (). The Kaplan-Meier estimate of reoperation rates at 5 years after surgery were also no different for the unilateral THAs compared with the second hips of staged bilateral THAs (3% [95% CI 2.8 to 3.2] for both groups). It was lower (2% [95% CI 1.8 to 2.3]) for a first hip of a staged bilateral THA. For the secondary outcome, the relative 5-year survival differed for all groups. It was 105% (95% CI 104.9 to 105.9) for patients with unilateral THA, 107% (95% CI 106.3 to 107.4) for patients with a second hip from a staged bilateral THA and 109% (95% CI 108.8 to 109.5) for patients with a first hip of a staged bilateral THA. Patients with only a first hip of a planned staged bilateral THA who did not survive long enough to undergo their second THA were classified as unilaterals. The rank-order of survival curves are therefore by design ("immortal time bias"). We conclude, however, that survival for patients with unilateral THA more closely resembles the survival of patients with a second hip of a staged bilateral THA, compared with the first. Conclusions Our findings, which are based on observational register data, challenge the common practice in epidemiologic studies of analyzing only the first hip of a staged bilateral THA. We recommend analyzing the second THA in a patient who has undergone staged bilateral THA rather than the first because the second procedure better resembles unilateral THA.
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| 9. |
- Bülow, Erik, et al.
(author)
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Comorbidity does not predict long-term mortality after total hip arthroplasty
- 2017
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 88:5, s. 472-477
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Journal article (peer-reviewed)abstract
- © 2017 The Author(s). Published by Taylor & Francis on behalf of the Nordic Orthopedic Federation. Background and purpose — In-hospital death following total hip arthroplasty (THA) is related to comorbidity. The long-term effect of comorbidity on all-cause mortality is, however, unknown for this group of patients and it was investigated in this study. Patients and methods — We used data from the Swedish Hip Arthroplasty Register, linked to the National Patient Register from the National Board of Health and Welfare, for patients operated on with THA in 1999–2012. We identified 120,836 THAs that could be included in the study. We evaluated the predictive power of the Charlson and Elixhauser comorbidity indices on mortality, using concordance indices calculated after 5, 8, and 14 years after THA. Results — All comorbidity indices performed poorly as predictors, in fact worse than a base model with age and sex only. Elixhauser was, however, the least bad choice and it predicted mortality with concordance indices 0.59, 0.58, and 0.56 for 5, 8, and 14 years after THA. Interpretation — Comorbidity indices are poor predictors of long-term mortality after THA.
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| 10. |
- Bülow, Erik, et al.
(author)
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Low predictive power of comorbidity indices identified for mortality after acute arthroplasty surgery undertaken for femoral neck fracture
- 2019
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In: Bone & Joint Journal. - 2049-4394. ; 101B:1, s. 104-112
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Journal article (peer-reviewed)abstract
- Aims Our aim was to examine the Elixhauser and Charlson comorbidity indices, based on administrative data available before surgery, and to establish their predictive value for mortality for patients who underwent hip arthroplasty in the management of a femoral neck fracture. We analyzed data from 42 354 patients from the Swedish Hip Arthroplasty Register between 2005 and 2012. Only the first operated hip was included for patients with bilateral arthroplasty. We obtained comorbidity data by linkage from the Swedish National Patient Register, as well as death dates from the national population register. We used univariable Cox regression models to predict mortality based on the comorbidity indices, as well as multivariable regression with age and gender. Predictive power was evaluated by a concordance index, ranging from 0.5 to 1 (with the higher value being the better predictive power). A concordance index less than 0.7 was considered poor. We used bootstrapping for internal validation of the results. The predictive power of mortality was poor for both the Elixhauser and Charlson comorbidity indices (concordance indices less than 0.7). The Charlson Comorbidity Index was superior to Elixhauser, and a model with age and gender was superior to both indices. Preoperative comorbidity from administrative data did not predict mortality for patients with a hip fracture treated by arthroplasty. This was true even if association on group level existed.
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