| 1. |
- Jerevall, Piiha-Lotta, et al.
(författare)
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Exploring the two-gene ratio in breast cancer – independent roles for HOXB13 and IL17BR in prediction of clinical outcome
- 2008
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Ingår i: Breast Cancer Research and Treatment. - : Institutionen för klinisk och experimentell medicin. - 0167-6806 .- 1573-7217. ; 107:2, s. 225-234
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Tidskriftsartikel (refereegranskat)abstract
- Background: The two-gene expression ratio HOXB13:IL17BR has been proposed to predict the outcome of tamoxifen-treated breast cancer patients. We intended to examine whether this ratio can predict the benefit of 5 years vs. 2 years of tamoxifen treatment of postmenopausal patients. A further objective was to investigate any prognostic effects of the ratio in systemically untreated premenopausal patients. Based on the current knowledge of HOXB13 and IL17BR, we hypothesized that these genes may have individual prognostic or predictive power. Patients and methods: Expression of HOXB13 and IL17BR were quantified by real-time PCR in tumors from 264 randomized postmenopausal patients and 93 systemically untreated premenopausal patients. Results: A high HOXB13:IL17BR ratio was associated with aggressive tumor characteristics, as were low levels of IL17BR alone. The ratio and HOXB13 alone predicted recurrence-free survival after endocrine treatment, with a benefit of prolonged treatment in estrogen receptor-positive patients correlated to a low ratio (recurrence rate ratio: RR=0.39; p=0.030), or low expression of HOXB13 (RR=0.37; p=0.015). No difference in recurrence-free survival was seen for the high ratio or high HOXB13 subgroups. The predictive value of HOXB13 and HOXB13:IL17BR was significant in multivariate analysis. In the systemically untreated cohort, only IL17BR showed independent prognostic significance. Conclusion: We conclude that the ratio or HOXB13 alone can predict the benefit of endocrine therapy, with a high ratio or a high expression rendering patients less likely to respond. We have also shown that IL17BR might be an independent prognostic factor in breast cancer.
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| 2. |
- Johansson, Ida, et al.
(författare)
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High-resolution genomic profiling of male breast cancer reveals differences hidden behind the similarities with female breast cancer
- 2011
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 129:3, s. 747-760
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Tidskriftsartikel (refereegranskat)abstract
- Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic information. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC arrays. Significant regions in common between cases were assessed using Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. A publicly available genomic data set of 359 FBC tumors was used for reference purposes. The data revealed a broad pattern of aberrations, confirming that MBC is a heterogeneous tumor type. Genomic gains were more common in MBC than in FBC and often involved whole chromosome arms, while losses of genomic material were less frequent. The most common aberrations were similar between the genders, but high-level amplifications were more common in FBC. We identified two genomic subgroups among MBCs; male-complex and male-simple. The male-complex subgroup displayed striking similarities with the previously reported luminal-complex FBC subgroup, while the male-simple subgroup seems to represent a new subgroup of breast cancer occurring only in men. There are many similarities between FBC and MBC with respect to genomic imbalances, but there are also distinct differences as revealed by high-resolution genomic profiling. MBC can be divided into two comprehensive genomic subgroups, which may be of prognostic value. The male-simple subgroup appears notably different from any genomic subgroup so far defined in FBC.
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| 3. |
- Klintman, Marie, et al.
(författare)
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The Prognostic Value of Mitotic Activity Index (MAI), Phosphohistone H3 (PPH3), Cyclin B1, Cyclin A, and Ki67, Alone and in Combinations, in Node-Negative Premenopausal Breast Cancer
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Proliferation, either as the main common denominator in genetic profiles, or in the form of single factors such as Ki67, is recommended for clinical use especially in estrogen receptor-positive (ER) patients. However, due to high costs of genetic profiles and lack of reproducibility for Ki67, studies on other proliferation factors are warranted. The aim of the present study was to evaluate the prognostic value of the proliferation factors mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in combinations. In 222 consecutive premenopausal node-negative breast cancer patients (87% without adjuvant medical treatment), MAI was assessed on whole tissue sections (predefined cut-off >= 10 mitoses), and PPH3, cyclin B1, cyclin A, and Ki67 on tissue microarray (predefined cut-offs 7th decile). In univariable analysis (high versus low) the strongest prognostic proliferation factor for 10-year distant disease-free survival was MAI (Hazard Ratio (HR)=3.3, 95% Confidence Interval (CI): 1.8-6.1), followed by PPH3, cyclin A, Ki67, and cyclin B1. A combination variable, with patients with MAI and/or cyclin A high defined as high-risk, had even stronger prognostic value (HR=4.2, 95% CI: 2.2-7). When stratifying for ER-status, MAI was a significant prognostic factor in ER-positive patients only (HR=7.0, 95% CI: 3.1-16). Stratified for histological grade, MAI added prognostic value in grade 2 (HR=7.2, 95% CI: 3.1-38) and grade 1 patients. In multivariable analysis including HER2, age, adjuvant medical treatment, ER, and one proliferation factor at a time, only MAI (HR=2.7, 95% CI: 1.1-6.7), and cyclin A (HR=2.7, 95% CI: 1.2-6.0) remained independently prognostic. In conclusion this study confirms the strong prognostic value of all proliferation factors, especially MAI and cyclin A, in all patients, and more specifically in ER-positive patients, and patients with histological grade 2 and 1. Additionally, by combining two proliferation factors, an even stronger prognostic value may be found.
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| 4. |
- Niméus, Emma, et al.
(författare)
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Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy
- 2008
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionSome patients with breast cancer develop local recurrence after breast-conservation surgery despite postoperative radiotherapy, whereas others remain free of local recurrence even in the absence of radiotherapy. As clinical parameters are insufficient for identifying these two groups of patients, we investigated whether gene expression profiling would add further information.MethodsWe performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation.ResultsWithin the estrogen receptor-positive (ER+) subgroup, the gene expression profile clearly distinguished patients with local recurrence after radiotherapy (n = 20) from those without local recurrence (n = 80 with or without radiotherapy). The receiver operating characteristic (ROC) area was 0.91, and 5,237 of 26,824 reporters had a P value of less than 0.001 (false discovery rate = 0.005). This gene expression profile provides substantially added value to conventional clinical markers (for example, age, histological grade, and tumor size) in predicting local recurrence despite radiotherapy. Within the ER- subgroup, a weaker, but still significant, signal was found (ROC area = 0.74). The ROC area for distinguishing patients who develop local recurrence from those who remain local recurrence-free in the absence of radiotherapy was 0.66 (combined ER+/ER-).ConclusionA highly distinct gene expression profile for patients developing local recurrence after breast-conservation surgery despite radiotherapy has been identified. If verified in further studies, this profile might be a most important tool in the decision making for surgery and adjuvant therapy.
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| 5. |
- Rydén, Lisa, et al.
(författare)
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Reproducibility of human epidermal growth factor receptor 2 analysis in primary breast cancer: a national survey performed at pathology departments in Sweden.
- 2009
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:6, s. 860-6
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Tidskriftsartikel (refereegranskat)abstract
- HER2 is a treatment predictive factor for the effect of trastuzumab and associated with poor prognosis in breast cancer. The analysis of HER2 must be performed with good quality, with regard to both the immunohistochemical (IHC) and in situ hybridization (ISH) analysis.A tissue microarray (TMA) including 11 breast cancer samples was sent twice (once in 2005 and again in 2006) to 24 pathology departments in Sweden. A questionnaire was also sent to the departments in 2006.With IHC, all departments reported the same results (0/1+ vs. 2+ vs. 3 + ) for three (2005) and six samples (2006). The mean kappa-value increased from 0.67 to 0.77, indicating a good reproducibility at both occasions. With fluorescence-ISH (FISH), the 11 departments using this technique reported the same results (amplified vs. normal) for nine (2005) and ten samples (2006). The mean kappa-value showed very good reproducibility both 2005 and 2006 (0.92 and 0.96, respectively). Based on the answers from the participating departments, the questionnaire revealed that 31% of primary breast cancer diagnosed in 2006 (n = 5 043) were 2 + /3+. FISH analysis of 2+ confirmed 12% of the samples to be amplified. The corresponding figure for 3 + was 90%. In total, 14.3% of the samples were HER2 positive (2+ and amplified, or 3 + ).The results obtained in this study indicate that the reproducibility for HER2 analysis is good (IHC) and very good (FISH) between the pathology departments in Sweden using TMA-based tumor samples. In 2006, 14.3% of invasive breast cancers were HER2 positive.
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| 6. |
- Strand, Carina, et al.
(författare)
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Combination of the proliferation marker cyclin A, histological grade, and estrogen receptor status in a new variable with high prognostic impact in breast cancer
- 2012
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 131:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- Global gene expression profiles, consisting mainly of genes associated with proliferation, have been shown to subdivide histological grade 2 breast cancers into groups with different prognosis. We raised the question whether this subdivision could be done using a single proliferation marker, cyclin A. Furthermore, we combined cyclin A (CA), histological grade (G), and estrogen receptor-ER (E) into a new variable, CAGE. Our aim was to investigate not only the prognostic importance of cyclin A alone but also the value of the combination variable CAGE. In 219 premenopausal node-negative patients, cyclin A was assessed using immunohistochemistry on tissue microarrays. High cyclin A was defined as above the seventh decile of positive cells. Only 13% of the patients received adjuvant systemic therapy. Cox proportional hazards regression was used to model the impact of the factors on distant disease-free survival (DDFS). Cyclin A divided histological grade 2 tumors into two groups with significantly different DDFS (hazard ratio [HR]: 15, P < 0.001). When stratifying for ER status, cyclin A was a prognostic factor only in the ER positive subgroup. We found that CAGE was an independent prognostic factor for DDFS in multivariate analysis (HR: 4.1, P = 0.002), together with HER2. CAGE and HER2 identified 53% as low-risk patients with a 5-year DDFS of 95%. A new prognostic variable was created by combining cyclin A, histological grade, and ER (CAGE). CAGE together with HER2 identified a large low-risk group for whom adjuvant chemotherapy will have limited efficacy and may be avoided.
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| 7. |
- Strand, Carina, et al.
(författare)
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The combination of Ki67, histological grade and estrogen receptor status identifies a low-risk group among 1,854 chemo-naive women with N0/N1 primary breast cancer
- 2013
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Ingår i: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to confirm a previously defined prognostic index, combining a proliferation marker, histological grade, and estrogen receptor (ER) in different subsets of primary N0/N1 chemo-naive breast cancer patients. Methods/design: In the present study, including 1,854 patients, Ki67 was used in the index (KiGE), since it is the generally accepted proliferation marker in clinical routine. The low KiGE-group was defined as histological grade 1 patients and grade 2 patients which were ER-positive and had low Ki67 expression. All other patients made up the high KiGE-group. The KiGE-index separated patients into two groups with different prognosis. In multivariate analysis, KiGE was significantly associated with disease-free survival, when adjusted for age at diagnosis, tumor size and adjuvant endocrine treatment (hazard ratio: 3.5, 95% confidence interval: 2.6-4.7, P<0.0001). Discussion: We have confirmed a prognostic index based on a proliferation marker (Ki67), histological grade, and ER for identification of a low-risk group of patients with N0/N1 primary breast cancer. For this low-risk group constituting 57% of the patients, with a five-year distant disease-free survival of 92%, adjuvant chemotherapy will have limited effect and may be avoided.
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| 8. |
- Andersson, Jan, et al.
(författare)
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Traffic safety effects when overtaking 30 meter trucks
- 2012
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Ingår i: Advances in Human Factors and Ergonomics 2012- 14 Volume Set. - : Taylor & Francis. - 146655262X - 9781466552623
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Konferensbidrag (refereegranskat)abstract
- The purpose of this paper is to investigate if the introduction of extra-long and heavy trucks has an effect on traffic safety on Swedish roads, especially in relation to overtaking maneuvers. Traffic safety effects will be measured in terms of road user behavior concerning accelerations and time slots. First, focus group interviews with heavy truck drivers. Truck drivers that do not drive extra-long trucks believe that the introduction of extra-long trucks will create a number of traffic safety problems especially in terms of conflicts with ordinary road users. The drivers of extra-long trucks do not experience the problems that ordinary truck drivers predict. The problems they experience can be taken care of with more planning (thinking ahead). They also believe that the traffic sign on the back of the extra-long vehicle has a positive effect. The truck company, working environment and truck equipment are other important aspects mentioned by the drivers of the extra-long vehicles.The simulator study investigates overtaking situations on a 2+1-lane highway, with extra-long trucks (30.4 m) and ordinary trucks (18.75 m). The results reveal that the distance from the rear/front of the truck to the point where only one lane exists affects car drivers’ decision to overtake, independently of truck length. If the truck is in the relatively same position, the timeslot for a safe overtaking maneuver before next one-lane section was reduced significantly for extra-long trucks compared to ordinary trucks. The conclusion is that there exist small tendencies which point in the direction of enhanced traffic safety problems with the introduction of extra-long trucks. The results should, however, be interpreted with caution as the number of data points was few and collected in specific situations and in specific conditions. It was neither considered how the introduction of longer and heavier trucks, given a constant amount of goods, reduces the number of heavy trucks on the road network.
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| 9. |
- Andersson, Jan, et al.
(författare)
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Trafiksäkerhetspåverkan vid omkörning av 30-metersfordon
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Trafikverket överväger att tillåta längre och tyngre fordon på vägarna förutsatt att de inte påverkar trafiksäkerheten negativt. Syftet med studien var att undersöka säkerhetseffekten av fordonslängd, speciellt med avseende på olycksrisken vid omkörningar. Intervjuade förare av en 30-meters timmerbil hade inte upplevt de farhågor som förare av normallånga lastbilar uttryckt i samband med trånga rondeller och korsningar, men de nämner betydelsen av stödjande åkeri, arbetsmiljö och fordonsutrustning. En simulatorstudie studerade bilförares omkörningar av ett 30- och ett 18,75-metersfordon på en 2+1-väg i situationen då två körfält går ihop till ett. Tidluckan till ett återstående körfält var i genomsnitt 0,2 s (sign.) kortare efter omkörningar av 30-metersfordonet i situationer då bakänden var i samma relativa position som för 18,75-metersfordonet vid början av omkörningen. En fältstudie analyserade videoinspelade omkörningar av en 30- och en 24-meters timmerbil på en 2+1-väg och en tvåfältig väg. Ingen signifikant skillnad i tidluckor kunde påvisas mellan omkörningar av de två fordonen för någon av vägtyperna. Det senare resultatet ska dock tolkas med försiktighet på grund av ojämnt distribuerad data som insamlats under specifika förhållanden. Slutsatserna är att det finns en liten tendens till negativ säkerhetseffekt vid omkörningar av längre fordon, och att fler fältstudier är nödvändiga.
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| 10. |
- Larsson, Carina, 1969-, et al.
(författare)
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Communicating continuous improvement in manufacturing companies : Divergencies between current practice and theory
- 2017
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Konferensbidrag (refereegranskat)abstract
- Succeeding with continuous improvement is important for manufacturing companies to increase the competitive edge. In order to succeed with continuous improvement, literature shows that communication of improvement indicators need to be integrated with communication of control indicators. This paper identifies divergencies between current practice and theory in the communication of CI, which can be a reason for why manufacturing companies fail in their CI implementation. An integration of control indicators and improvement indicators could improve continuous improvement results, increasing business performance.
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