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Sökning: WFRF:(Fjällskog Marie Louise)

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  • Föregående 12345[6]7Nästa
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51.
  • Hellerstedt-Börjesson, Susanne, et al. (författare)
  • Women with Breast Cancer : Experience of Chemotherapy-Induced Pain - Triangulation of Methods
  • 2015
  • Ingår i: Cancer Nursing. - 0162-220X .- 1538-9804. ; 38:1, s. 31-39
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Chemotherapy treatment for cancer diseases can cause body pain during adjuvant therapy. OBJECTIVE: The aim was to describe the perceived impact of adjuvant chemotherapy-induced pain (CHIP) on the daily lives of women with newly diagnosed breast cancer, using triangulation. METHOD: Fifty-seven women scheduled for chemotherapy in doses of 75 mg/m or greater of epirubicin and/or docetaxel participated. Twenty-two of these women registered pain with values of 4 or more on the visual analog scale on day 10 following chemotherapy. Of these 22, 16 participated in an interview and colored a printed body image. A qualitative thematic stepwise analysis of the interviews was performed. RESULTS: Chemotherapy-induced pain had a profound impact on daily life. Ten women reported the worst possible pain, with visual analog scale scores of 8 to 10. Three different categories crystallized: perception (A) of manageable pain, which allowed the women to maintain their daily lives; perception (B) of pain beyond imagination, whereby the impact of pain had become more complex; and perception (C) of crippling pain, challenging the women's confidence in survival. CONCLUSIONS: The findings highlight the inability to capture CHIP with 1 method only; it is thus necessary to use complimentary methods to capture pain. We found that pain had a considerable impact on daily life, with surprisingly high scores of perceived pain, findings that to date have been poorly investigated qualitatively. IMPLICATIONS FOR PRACTICE: Nurses need to (1) better identify, understand and treat CHIP, using instruments and protocols; and (2) provide improved communication about pain and pain management.</p>
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52.
  • Johansson, Ida, et al. (författare)
  • Gene expression profiling of primary male breast cancers reveals two unique subgroups and identifies N-acetyltransferase-1 (NAT1) as a novel prognostic biomarker
  • 2012
  • Ingår i: Breast Cancer Research. - 1465-5411 .- 1465-542X. ; 14:1, s. R31
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>INTRODUCTION:</strong></p><p>Male breast cancer (MBC) is a rare and inadequately characterized disease. The aim of the present study was to characterize MBC tumors transcriptionally, to classify them into comprehensive subgroups, and to compare them with female breast cancer (FBC).</p><p><strong>METHODS:</strong></p><p>A total of 66 clinicopathologically well-annotated fresh frozen MBC tumors were analyzed using Illumina Human HT-12 bead arrays, and a tissue microarray with 220 MBC tumors was constructed for validation using immunohistochemistry. Two external gene expression datasets were used for comparison purposes: 37 MBCs and 359 FBCs.</p><p><strong>RESULTS:</strong></p><p>Using an unsupervised approach, we classified the MBC tumors into two subgroups, luminal M1 and luminal M2, respectively, with differences in tumor biological features and outcome, and which differed from the intrinsic subgroups described in FBC. The two subgroups were recapitulated in the external MBC dataset. Luminal M2 tumors were characterized by high expression of immune response genes and genes associated with estrogen receptor (ER) signaling. Luminal M1 tumors, on the other hand, despite being ER positive by immunohistochemistry showed a lower correlation to genes associated with ER signaling and displayed a more aggressive phenotype and worse prognosis. Validation of two of the most differentially expressed genes, class 1 human leukocyte antigen (HLA) and the metabolizing gene N-acetyltransferase-1 (NAT1), respectively, revealed significantly better survival associated with high expression of both markers (HLA, hazard ratio (HR) 3.6, P = 0.002; NAT1, HR 2.5, P = 0.033). Importantly, NAT1 remained significant in a multivariate analysis (HR 2.8, P = 0.040) and may thus be a novel prognostic marker in MBC.</p><p><strong>CONCLUSIONS: </strong></p><p>We have detected two unique and stable subgroups of MBC with differences in tumor biological features and outcome. They differ from the widely acknowledged intrinsic subgroups of FBC. As such, they may constitute two novel subgroups of breast cancer, occurring exclusively in men, and which may consequently require novel treatment approaches. Finally, we identified NAT1 as a possible prognostic biomarker for MBC, as suggested by NAT1 positivity corresponding to better outcome.</p>
53.
  • Johansson, Ida, et al. (författare)
  • Genome methylation patterns in male breast cancer - Identification of an epitype with hypermethylation of polycomb target genes
  • 2015
  • Ingår i: Molecular Oncology. - 1574-7891 .- 1878-0261. ; 9:8, s. 1565-1579
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Male breast cancer (hoc) is a rare disease that shares both similarities and differences with female breast cancer (FBC). The aim of this study was to assess genome-wide DNA methylation profiles in MBC and compare them with the previously identified transcriptional subgroups of MBC, luminal M1 and M2, as well as the intrinsic subtypes of FBC. Illumina's 450K Infinium arrays were applied to 47 MBC and 188 FBC tumors. Unsupervised clustering of the most variable CpGs among MBC tumors revealed two stable epitypes, designated ME1 and ME2. The methylation patterns differed significantly between the groups and were closely associated with the transcriptional subgroups luminal M1 and M2. Tumors in the ME1 group were more proliferative and aggressive than ME2 tumors, and showed a tendency toward inferior survival. ME1 tumors also displayed hypermethylation of PRC2 target genes and high expression of EZH2, one of the core components of PRC2. Upon combined analysis of MBC and FBC tumors, ME1 MBCs clustered among luminal B FBC tumors and ME2 MBCs clustered within the predominantly luminal A FBC cluster. The majority of the MBC tumors remained grouped together within the clusters rather than being interspersed among the FBC tumors. Differences in the genomic location of methylated CpGs, as well as in the regulation of central canonical pathways may explain the separation between MBC and FBC tumors in the respective clusters. These findings further suggest that MBC is not readily defined using conventional criteria applied to FBC.</p>
54.
  • Johansson, Ida, et al. (författare)
  • Genome methylation patterns in male breast cancer - Identification of an epitype with hypermethylation of polycomb target genes.
  • 2015
  • Ingår i: Molecular Oncology. - Elsevier. - 1574-7891. ; 9:8, s. 1565-1579
  • Tidskriftsartikel (refereegranskat)abstract
    • Male breast cancer (MBC) is a rare disease that shares both similarities and differences with female breast cancer (FBC). The aim of this study was to assess genome-wide DNA methylation profiles in MBC and compare them with the previously identified transcriptional subgroups of MBC, luminal M1 and M2, as well as the intrinsic subtypes of FBC. Illumina's 450K Infinium arrays were applied to 47 MBC and 188 FBC tumors. Unsupervised clustering of the most variable CpGs among MBC tumors revealed two stable epitypes, designated ME1 and ME2. The methylation patterns differed significantly between the groups and were closely associated with the transcriptional subgroups luminal M1 and M2. Tumors in the ME1 group were more proliferative and aggressive than ME2 tumors, and showed a tendency toward inferior survival. ME1 tumors also displayed hypermethylation of PRC2 target genes and high expression of EZH2, one of the core components of PRC2. Upon combined analysis of MBC and FBC tumors, ME1 MBCs clustered among luminal B FBC tumors and ME2 MBCs clustered within the predominantly luminal A FBC cluster. The majority of the MBC tumors remained grouped together within the clusters rather than being interspersed among the FBC tumors. Differences in the genomic location of methylated CpGs, as well as in the regulation of central canonical pathways may explain the separation between MBC and FBC tumors in the respective clusters. These findings further suggest that MBC is not readily defined using conventional criteria applied to FBC.
55.
  • Johansson, Ida, et al. (författare)
  • High-resolution genomic profiling of male breast cancer reveals differences hidden behind the similarities with female breast cancer
  • 2011
  • Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 129:3, s. 747-760
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p>
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56.
  • Koliadi, Anthoula, et al. (författare)
  • Cyclin B is an immunohistochemical proliferation marker which can predict for breast cancer death in low-risk node negative breast cancer
  • 2010
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 49:6, s. 816-820
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Patients with low-risk node negative breast cancer have an excellent prognosis with 5% breast cancer mortality at 10 years. However, prognostic factors are needed to identify poor prognostic patients who might benefit from adjuvant systemic therapy. Proliferation has been identified as the most important component of gene expression profiles. Cyclin B is a proliferative marker easily assessed by immunohistochemistry. We wanted to examine cyclin B as a prognostic factor in low-risk breast cancer patients. Patients and methods. Using an experimental study design, we compared women dying early from their breast cancer (n=17) with women free from relapse more than eight years after initial diagnosis (n=24). All women had stage I, node negative and hormone receptor positive disease. None had received adjuvant chemotherapy. Tumor samples were immunostained for cyclin B using commercial antibodies. Results. The mean percentage of cyclin B (12%) was significantly higher (p=0.001) in women dying from their breast cancer compared with women free from relapse ( 5%). High cyclin B (&gt;= 9%) identified 11/17 patients dying from breast cancer and low cyclin B identified 22/24 patients free from relapse. The sensitivity and specificity of cyclin B was 65% and 92%, respectively. Discussion. We found that low-risk node negative patients with high expression of cylin B had a significantly worse outcome than patients with low expression of cyclin B. Cyclin B could separate patients with poor survival from those with good survival with 80% accuracy. We suggest that cyclin B might be a potent prognostic factor in this low-risk patient group.</p>
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57.
  • Koliadi, Anthoula (författare)
  • The Prognostic Impact of Proliferation Markers in Breast Cancer with Emphasis on Cyclin B1 and PPH3
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The aim of this thesis was to investigate the prognostic role of the proliferation markers cyclin B1 and Phosphorylated Histone 3 (PPH3) in breast cancer (BC).</p><p>In paper I we used an experimental study design, we compared women dying early from their BC with women free from relapse more than eight years after initial diagnosis. All women had stage I, node-negative and hormone receptor positive disease. None had received adjuvant chemotherapy. We found that low-risk node negative patients with high expression of cyclin B1 had a significantly worse outcome than patients with low expression of cyclin B1.</p><p>In paper II a population-based case control study was performed to further investigate the prognostic value of cyclin B1. One hundred and ninety women who died from BC were defined as cases and 190 women alive at the time for the corresponding case’s death were defined as controls. Inclusion criteria were tumor size 50 mm, no lymph node metastases, and no adjuvant chemotherapy. Two investigators evaluated the stainings independently. Cyclin B1 was found to be a prognostic factor for BC death that could identify high-risk patients with a good to very good reproducibility.</p><p>Paper III aimed to investigate the role of proliferation in male breast cancer (MBC). One hundred and ninety-seven MBC tumors were stained for cyclin A, B1, D1 and Ki67. Overexpression of cyclin A and B1 and elevated mitotic count were predictive of breast cancer death. Ki67 was re-evaluated and different cut-offs were used, but no prognostic value could be demonstrated. On the other hand high levels of cyclin D1 were associated with better outcome in MBC.</p><p>In paper IV we applied the immunohistochemichal panel suggested from international guidelines to the same patient material as in paper II, to discriminate luminal A from luminal B BC. We wanted to evaluate if different cut-off values of Ki67, cyclin A or B1 could more clearly separate luminal A from B. Cyclin A, B1 and Ki67 (cut-off 20%) could detect difference in outcome between these subtypes with cyclin A showing greater prognostic value.</p><p>The aim of paper V was to examine the prognostic role of PPH3 compared to the proliferation markers Ki67, cyclin A and cyclin B1 with focus on ER positive disease. PPH3 was found to be a prognostic factor for breast cancer death but in the multivariate analysis including all proliferation markers, only cyclin A remained a prognostic factor.</p><p>Finally, we conclude that both cyclin B1 and PPH3 are prognostic factors for breast cancer death, but are outperformed by cyclin A in ER positive patients. In male breast cancer prognostic factors need to be further studied. </p>
58.
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59.
  • Nilsson, Cecilia, 1971- (författare)
  • Characterization of Male Breast Cancer From Molecule to Clinical Outcome
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The aim of this thesis was to investigate different aspects of male breast cancer (MBC), and to compare these with findings in female breast cancer (FBC). In paper I, a population–based study was performed to investigate possible differences in treatment and outcome between MBC and FBC patients. MBC and FBC presented with a similar distribution of stage. Although no differences in primary treatment strategy were demonstrated, MBC patients had significantly poorer overall and relative survival, indicating a more aggressive disease. Paper II aimed to assess the value of clinicopathological factors and molecular subtypes in MBC. One hundred and ninety-seven MBC tumors were characterized using immunohistochemistry (IHC) and the findings were correlated to outcome. Lymph node positivity, larger tumor size and ER-negativity were independent risk factors for breast cancer death. Tumor grade, HER2, Ki 67 or IHC classification into molecular subtypes did not demonstrate any prognostic information. In paper III, the same patient material as in paper II was used for evaluation of proliferation markers. High levels of cyclin A and cyclin B expression and an elevated mitotic count were predictive of breast cancer death. Ki-67 was re-evaluated using different cut-offs, but no prognostic value could be demonstrated. Contrarily, overexpression of cyclin D1 was associated with a lower risk of breast cancer death. In papers IV-V, the molecular background of MBC tumors was investigated.  Global GEX analyses were performed and two novel subgroups of MBC tumors were identified; luminal M1 and luminal M2. When comparing the degree of similarity with the “intrinsic” subtypes in FBC tumors, more than half of the MBC tumors remained unclassified.  Comparative genomic hybridization was used to investigate DNA aberrations. Two MBC subgroups were identified, of which one did not resemble any of the female subgroups. In both studies on the molecular level, a majority of patients were classified into the subgroup with a more aggressive tumor behavior. In conclusion, MBC seems to be a unique tumor entity. The established molecular subtypes in FBC are not applicable in MBC. Other prognostic profiles, specific for MBC, need to be identified.</p><p> </p>
60.
  • Nilsson, Cecilia, et al. (författare)
  • High proliferation is associated with inferior outcome in male breast cancer patients
  • 2013
  • Ingår i: Modern Pathology. - 0893-3952 .- 1530-0285. ; 26:1, s. 87-94
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Assessment of proliferation is important in female breast cancer and individual treatment decisions are based upon its results, especially in the lumina! subgroups. Gene expression analyses fail to group male breast cancer into the intrinsic subgroups previously established in female breast cancer. Even though proliferation has been shown to divide malebreast cancer into molecular subgroups with different prognoses, the clinical importance ofproliferation markers has not yet been elucidated. Previous studies in male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The aim of the present project was to studyproliferation in male breast cancer by assessing other proliferation-related markers viz. cyclins A, B, D1 and mitotic count. A total of 197 male breast cancer cases with accessible paraffin-embedded material and outcome data were investigated. Immunohistochemical stainings were performed on tissue microarrays. Kaplan-Meier estimates and the Cox proportional regression models were used for survival analyses with breast cancer death as the event. The subset ofpatients with high expression of cyclin A (hazard ratio (HR) 3.7; P=0.001) and B (HR 2.7; P=0.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR 2.5; P=0.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR 0.3; P=0.001). In conclusion, high levels of cyclin A and B expression and an elevated mitotic count result in a two to threefold higher risk forbreast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs further elucidation. </p>
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