| 1. |
- Bergenfelz, Caroline, et al.
(författare)
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Systemic Monocytic-MDSCs Are Generated from Monocytes and Correlate with Disease Progression in Breast Cancer Patients.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14+HLA-DRlow/-CD86low/-CD80low/-CD163low/-) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression.
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| 2. |
- Antoniou, A. C., et al.
(författare)
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Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers : Implications for risk prediction
- 2010
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 70:23, s. 9742-9754
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Tidskriftsartikel (refereegranskat)abstract
- The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased breast cancer risk for BRCA2 carriers (per-allele HR = 1.10, 95% CI: 1.03-1.18, P = 0.006 and HR = 1.09, 95% CI: 1.01-1.19, P = 0.03, respectively). Neither SNP was associated with breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10-11 - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers.
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| 3. |
- Bergman, Malin, 1967-
(författare)
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Genetic polymorphism and breast cancer risk in young women
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most common malignancy among women in the western world. Although the disease is rare in young women, it is one of the main causes of death at young age. The early onset breast cancer has demonstrated more aggressive pathological features than the late onset disease. These observations have raised the hypothesis that the biological background may differ between age categories.Breast carcinogenesis is a micro-evolutionary process that requires accumulation of DNA-damage and other epigenetic changes that promote cell survival and proliferation. The complexity of the disease makes it difficult to identify specific risk factors. Nevertheless, a large and compelling body of epidemiological and experimental data suggests that the cumulative dose of oestrogen is one key factor in the aetiology. Also, substantial data indicates that oxidative stress, from phosphorylation or other metabolic processes, is involved in the development of breast cancer. In young women, there is a strong genetic influence of breast cancer risk and beside mutations in highly penetrant genes, polymorphisms in a number of crucial genes may modify an individual's risk. Such modifier genes, associated with a more modest risk and high prevalence in the population, may contribute to a large proportion of the disease in the population. Identification of such predisposing polymorphisms may be an important step forward in identifiying individuals at risk. In the present thesis genetic polymorphisms in four different genes and their relation to early onset breast cancer, were analysed.In the first study, a polymorphism with a TaqI restriction site in the vitamin D3 receptor (VDR) gene was studied. VDR and its ligand, 1,25(OH)2D3, have been suggested to be important factors for differentiation of the breast epithelium and may suppress mammary tumorigenesis. The presence of a TaqI restriction site has been shown to correlate with increased transcriptional activity and mRNA stability of VDR, as well as high serum levels of 1,25(OH)2D3 and this high receptor activity may be protective against breast cancer. In the present study VDR TaqI polymorphism did not predict risk of early onset breast cancer. However, the results indicate an association between lymph node metastasis and genotype. In the second study, a promoter polymorphism in the CYP17 gene, which may influence the oestrogen synthesis, has been analysed. The polymorphism was correlated to the risk of early onset breast cancer, and the risk increased in a dose dependent manner. The fmdings indicated also a trend for risk allele carriers to have ER-negative and large tumours. Oestrogens are metabolized to potentially carcinogenic catecholoestrogens, which could be inactivated by and O-methylation, catalysed by Catechol-O-methyltransferase (COMT). This gene contains a variant which encode for a protein with decreased activity and is therefore predicted to be a risk allele. In the third study, the investigation of allele frequencies of the polymorphic COMT gene did not show any epidemiological evidences of implication in breast cancer. Finally; increasing numbers of studies indicate an important role for MnSOD in a number of cancer cell types. A genetic variant of MnSOD results in a less efficient transport into the mitochondria which may lead to an insufficient scavenging of free radicals. In this study, the mitochondrial targeting polymorphism was associated with risk of breast cancer in young women.In conclusion, genetic polymorphism in crucial genes may have impact on the risk of early onset breast cancer. Furthermore, some genotypes seems to influences the progression and outcome of the disease.
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| 4. |
- Björner, Sofie, et al.
(författare)
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Body mass index influences the prognostic impact of combined nuclear insulin receptor and estrogen receptor expression in primary breast cancer
- 2017
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 8:NOV
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic importance of tumor-specific nuclear insulin receptor (InsR) expression in breast cancer is unclear, while membrane and cytoplasmic localization of InsR is better characterized. The insulin signaling network is influenced by obesity and may interact with the estrogen receptor a (ERα) signaling. The purpose was to investigate the interplay between nuclear InsR, ER, body mass index (BMI), and prognosis. Tumor-specific expression of nuclear InsR was evaluated by immunohistochemistry in tissue microarrays from 900 patients with primary invasive breast cancer without preoperative treatment, included in a population-based cohort in Sweden (2002-2012) in relation to prognosis. Patients were followed for up to 11 years during which 107 recurrences were observed. Nuclear InsR+ expression was present in 214 patients (23.8%) and increased with longer time between surgery and staining (P < 0.001). There were significant effect modifications by ER status and BMI in relation to clinical outcomes. Nuclear InsR+ conferred higher recurrence-risk in patients with ER+ tumors, but lower risk in patients with ER- tumors (Pinteraction = 0.003). Normal-weight patients with nuclear InsR+ tumors had higher recurrence-risk, while overweight or obese patients had half the recurrence-risk compared to patients with nuclear InsR- tumors (Pinteraction = 0.007). Normal-weight patients with a nuclear InsR-/ER+ tumor had the lowest risk for recurrence compared to all other nuclear InsR/ER combinations [HRadj 0.50, 95% confidence interval (CI): 0.25-0.97], while overweight or obese patients with nuclear InsR-/ER- tumors had the worst prognosis (HRadj 7.75, 95% CI: 2.04-29.48). Nuclear InsR was more prognostic than ER among chemotherapy-treated patients. In summary, nuclear InsR may have prognostic impact among normal-weight patients with ER+ tumors and in overweight or obese patients with ER- tumors. Normal-weight patients with nuclear InsR-/ER+ tumors may benefit from less treatment than normal-weight patients with other nuclear InsR/ER combinations. Overweight or obese patients with nuclear InsR-/ER- tumors may benefit from more tailored treatment or weight management.
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| 5. |
- Björner, Sofie, et al.
(författare)
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Coffee is associated with lower breast tumor insulin-like growth factor receptor 1 levels in normal-weight patients and improved prognosis following tamoxifen or radiotherapy treatment
- 2018
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 9:JUN
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Tidskriftsartikel (refereegranskat)abstract
- Coffee is associated with decreased breast cancer risk, but the impact of body mass index (BMI) in combination with coffee consumption on prognosis is unclear. The suppressive effect of coffee constituents on the insulin-like growth factor receptor 1 (IGF1R) levels in breast cancer cells may play a role. The aim was to investigate the prognostic impact of coffee consumption and possible associations with tumor-specific IGF1R protein expression and BMI in a population-based cohort in Sweden, comprising 1,014 primary breast cancer patients without pretreatment enrolled 2002-2012 and followed for up to 13 years. Patients with higher coffee consumption had lower tumor IGF1R levels (P = 0.025), but only among the normal-weight patients (P = 0.005). Coffee did not impact the recurrence-risk overall. However, tamoxifen-treated patients with ER+ tumors drinking ≥ 2 cups of coffee/day had lower recurrence-risk [adjusted HR (HRadj) 0.57, 95% CI, 0.34-0.97] compared with patients with lower intake, although only among normal-weight patients (HRadj 0.37, 95% CI: 0.17-0.78; Pinteraction = 0.039). Similarly, coffee consumption ≥ 2 cups/day was associated with significantly lower recurrence-risk among the 640 radiotherapy-treated patients irrespective of BMI (HRadj 0.59, 95% CI 0.36-0.98) and in the 296 normal-weight patients (HRadj 0.36, 95% CI 0.17-0.76) but not in the 329 overweight or obese patients (HRadj 0.88, 95% CI 0.42-1.82) although the interaction was not significant (Pinteraction = 0.093). In conclusion, coffee consumption was negatively associated with tumor-specific IGF1R levels only among normal-weight patients. Though, IGF1R did not explain the association between coffee intake and improved prognosis among normal-weight tamoxifen- or radiotherapy-treated patients. Studies of IGF1R-targeting therapies may benefit from taking BMI and coffee consumption into account.
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| 6. |
- Björner, Sofie, et al.
(författare)
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Combined and individual tumor-specific expression of insulinlike growth factor-I receptor, insulin receptor and phosphoinsulin- like growth factor-I receptor/insulin receptor in primary breast cancer : Implications for prognosis in different treatment groups
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:6, s. 9093-9107
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Tidskriftsartikel (refereegranskat)abstract
- Clinical trials examining insulin-like growth factor-I receptor (IGF1R)-targeting strategies have emphasized that better predictive biomarkers are required to improve patient selection. Immunohistochemical tumor-specific protein expression of IGF1R, insulin receptor (InsR), and phosphorylated IGF1R/InsR (pIGF1R/InsR) individually and combined in relation to breast cancer prognosis was evaluated in a populationbased cohort of 1,026 primary invasive breast cancer patients without preoperative treatment diagnosed in Sweden. IGF1R (n = 923), InsR (n = 900), and pIGF1R/InsR (n = 904) combined cytoplasmic and membrane staining was dichotomized. IGF1Rstrong/InsRmod/strong/pIGF1R/InsRpos tumors were borderline associated with 2-fold risk for events, HRadj (2.00; 95%CI 0.96-4.18). Combined IGF1R and pIGF1R/InsR status only impacted prognosis in patients with InsRmod/strong expressing tumors (Pinteraction = 0.041). IGF1Rstrong expression impacted endocrine treatment response differently depending on patients' age and type of endocrine therapy. Phospho-IGF1R/InsRpos was associated with lower risk for events among non-endocrine-treated patients irrespective of ER status, HRadj (0.32; 95%CI 0.16-0.63), but not among endocrinetreated patients (Pinteraction = 0.024). In non-endocrine-treated patients, pIGF1R/InsRpos was associated with lower risk for events after radiotherapy, HRadj (0.31; 95%CI 0.12-0.80), and chemotherapy, HRadj (0.29; 95%CI 0.09-0.99). This study highlights the complexity of IGF hetero-and homodimer signaling network and its interplay with endocrine treatment, suggesting that combinations of involved factors may improve patient selection for IGF1R-targeted therapy.
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| 7. |
- Borgquist, Signe, et al.
(författare)
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Given breast cancer, is fat better than thin? Impact of the estrogen receptor beta gene polymorphisms.
- 2013
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 137:3, s. 849-862
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Tidskriftsartikel (refereegranskat)abstract
- The role of estrogen receptor beta (ERβ) in breast cancer has been investigated since its identification in 1996. Studies based on protein expression have indicated that ERβ is a favorable prognostic marker. Further, ERβ expression is lower in obese breast cancer patients. Fewer studies have focused on the prognostic impact of ERβ polymorphisms. Therefore, we analyzed the associations between four previously identified haplotype tagging single nucleotide polymorphisms (htSNPs), associated haplo- and diplotypes, and breast cancer-free survival according to body constitution. The patient cohort included 634 women from the prospective breast cancer and blood study (BC Blood study, Sweden) with a median follow-up of 4.92 years. Four htSNPs (i.e., rs4986938, rs1256049, rs1256031, rs3020450) in the ESR2 gene and the correlating haplo- and diplotypes were analyzed and correlated to selected patient and tumor characteristics and to disease-free survival, including stratification for BMI. Based on the four htSNPs, seven haplotypes and eight diplotypes were identified. The patient and tumor characteristics were well-balanced across all geno- and haplotypes. Disease-free survival differed according to rs4986938 and rs1256031 (Log-Rank P = 0.045 and P = 0.041, respectively) and the number of haplotype copies of the wildtype CCGC and TCAC (Log-Rank P = 0.027 and P = 0.038, respectively). In the survival analyses stratified for BMI, significant survival differences between alleles were observed among overweight women (rs4986938 and rs1256031 with Log-Rank P = 0.001 and P = 0.001, respectively). The BMI-stratified survival analyses based on haplotypes showed shorter disease-free survival for overweight women with null copies of CCGC (Log-Rank P = 0.001) and for overweight women with any TCAC copy (Log-Rank P < 0.0001). Markedly impaired disease-free survival was found for genotypes in two out of four ESR2 htSNPs and for two haplotypes. ESR2 polymorphisms seem to divide patients into good and poor survivors based on BMI, stressing the need of taking host factors into consideration in the evaluation of prognostic markers.
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| 8. |
- Bradlow, HL, et al.
(författare)
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Comparison of plasma and urinary levels of 2-hydroxyestrogen and 16 alpha-hydroxyestrogen metabolites
- 2006
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192. ; 87:2, s. 135-146
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Tidskriftsartikel (refereegranskat)abstract
- A modified ELISA assay for measurement of the two estrogen metabolites 2-hydroxyestrone (2OHE1) and 16 alpha-hydroxyestrone (16 alpha OHE1) in plasma and serum has been developed. Previously, these have only been measured in urine. It is not known how well the measurements of these metabolites in urine and plasma are correlated. The goal of this study was to compare urinary and plasma levels of 2OHE1 and 16 alpha OHE1 and their ratios and to explore how they were affected by ethnicity, dietary and genetic factors, and medication use. Blood and urine samples were obtained from 511 nulliparous women, aged 17-35, from four ethnic groups during the same visit at the study center, on a random day of the menstrual cycle. The overall correlation between the 2OHE1/16 alpha OHE1 ratio in plasma and urine was fair (r(s) = 0.52; p < 0.0001). In general, the correlation between the 2OHE1/16 alpha OHE1 ratio in urine and plasma was higher among women not using oral contraceptives (OCs) (r(s) = 0.58; p < 0.0001) than among women currently using OCs (r(s) = 0.34; p < 0.0001). The correlation was highest for samples obtained during the mid-cycle in among non-OC users (r(s) = 0.83; p < 0.0001). Among non-OC users, the urinary 2OHE1/160 alpha OHE1 ratio was stable over the menstrual cycle while there was an increase in the plasma 2OHE1/16 alpha OHE1 ratio. The strongest factors predicting discordance between the urinary and plasma 2OHE1/16 alpha OHE1 ratios among non-OC users were a baseline urinary 20HE1/16 alpha OHE1 ratio in the three upper quartiles (p < 0.001), the menstrual cycle phase (p = 0.001), and the number of cups of coffee consumed per day (p = 0.006). Among current OC users, the strongest predictors of discordance between the urinary and plasma 2OHE1/16 alpha OHE1 ratios were a baseline urinary 2IHE1/16 alpha OHE1 ratio in the three lower quartiles (p < 0.001), being black (p = 0.001), and being Asian (p = 0.014). In conclusion, we found that the correlation between the two methods was fair and varied according to the baseline urinary 2OHE1/16 alpha OHE1 ratio, ethnic group, OC status, coffee consumption, and time of menstrual cycle when the samples were obtained. (C) 2005 Elsevier Inc. All rights reserved.
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| 9. |
- Bågeman, Erika, et al.
(författare)
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Absence of the common Insulin-like growth factor-1 19-repeat allele is associated with early age at breast cancer diagnosis in multiparous women.
- 2007
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 96, s. 712-717
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Tidskriftsartikel (refereegranskat)abstract
- Multiparity decreases the risk of breast cancer in white women, whereas it is a risk factor in black women < 50 years. Early-onset breast cancer (< 50 years) has been associated with high insulin-like growth factor-I (IGF-I) levels. Absence of the common IGFI 19 cytosine-adenine ( CA)- repeat allele (IGFI-19/-19) inverts the effect of several non-genetic factors on breast cancer risk but the interaction between IGFI-19/-19 and multiparity on breast cancer risk is unknown. As IGFI-19/-19, multiparity and early-onset breast cancer are more common in black than in white women, we aimed to study whether multiparity combined with IGFI-19/-19 increases the risk of early-onset breast cancer. Four hundred and three breast cancer patients diagnosed in Lund, Sweden, at age 25 - 99 years were genotyped for the IGFI CA-repeat length using fragment analysis. Overall, 12.9% carried the IGFI-19/-19 genotype. There was a highly significant interaction between multiparity and IGFI-19/-19 on age at breast cancer diagnosis ( P = 0.007). Among IGFI-19/-19 patients, multiparity was associated with a 9.2 year earlier age at diagnosis compared with uniparity or nulliparity ( P = 0.006). Multiparity combined with IGFI-19/-19 was associated with an early age at breast cancer diagnosis. If confirmed, IGFI-19/-19 may help identify a subgroup of women for earlier breast cancer screening.
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| 10. |
- Bågeman, Erika, et al.
(författare)
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Coffee Consumption and CYP1A2*1F Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status.
- 2008
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 17:4, s. 895-901
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Tidskriftsartikel (refereegranskat)abstract
- CYP1A2 plays a key role in the metabolism of both estrogen and coffee. Women with higher coffee intake and the CYP1A2*1F A/A genotype have a ratio of high 2-hydroxyestrone (2-OHE1) to 16alpha-OHE1. 2-OHE1 is a weak estrogen and may even block the estrogen receptor (ER), whereas 16alpha-OHE1 is procarcinogenic. We hypothesized that moderate to high coffee consumption (>/=2 cups per day) combined with the CYP1A2*1F A/A genotype would be associated with a later age at diagnosis and a greater proportion of ER-negative (ER-) tumors among patients with breast cancer. We genotyped 458 patients with breast cancer (age, 25-99 years) in Lund, Sweden, for CYP1A2*1F. Information on lifestyle factors and tumor characteristics were obtained from preoperative questionnaires and pathology reports. Among patients with CYP1A2*1F A/A (51.3%), moderate to high consumption was associated with a later age at diagnosis compared with low coffee consumption (59.8 versus 52.6 years, P = 0.0004). These patients were also more likely to have ER- tumors than patients with low consumption (14.7% versus 0%, P = 0.018). Coffee was not associated with ER status or age at diagnosis in patients with at least one C allele. Age at diagnosis was not associated with ER status in patients with CYP1A2*1F A/A, but younger patients (<50 years) with at least one C allele were more likely to have ER- tumors compared with older patients (odds ratio, 4.2; 95% confidence interval, 1.9-9.3; P = 0.0002). These findings raise the hypothesis that coffee slows the growth of ER-positive tumors in patients with CYP1A2*1F A/A and may have implications for breast cancer if confirmed.
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| 11. |
- Dellson, Pia, et al.
(författare)
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Patients' and physicians' disagreement on patients' understanding of clinical cancer trial information : A pairwise pilot study of mirroring subjective assessments compared with objective measurements
- 2019
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Informed consent is a prerequisite for patients included in clinical trials. Trial design, inclusion criteria and legal requirements are increasingly complex. This complexity challenges design and delivery of written and oral trial information to ensure understandable information. To evaluate the level of concordance between patients' and informing physicians' assessments regarding patient understanding of trial information, we carried out a study based on paired questionnaire data from patients and their physicians. These assessments of patient understanding were further correlated with patients' factual knowledge of the information provided. Methods: This pilot study included patients and physicians immediately after the patients had received information on one of 23 ongoing phase III randomised cancer trials at two Swedish sites. In total, 46 patients and 17 physicians contributed data based on two new questionnaires with seven mirroring questions, where concordance was analysed with McNemar's test. These assessments of patients' self-estimated understanding were further correlated with the Patient Understanding of Research (Q-PUR) questionnaire that assesses factual knowledge of the information provided. Results: For each question, 47-61% of the patient-physician pairs were in concordance regarding their assessments of patients' 'fully understanding' or 'not fully understanding' various aspects of the trial information. For the discordant pairs, the physicians rated patient understanding lower than the patients themselves, for all seven questions. This difference was significant for five of the questions (P ≤ 0.017). The median Q-PUR knowledge score was 11 out of 12, but this score did not significantly correlate with the assessments, either from patients or from physicians. Conclusions: This study demonstrated a trend for physicians to rate the level of understanding of trial information among potential trial patients lower than the patients themselves. Application of Q-PUR revealed high knowledge scores, but without correlation to the assessments. These findings need validation in an independent setting, with an improved instrument with mirroring questions, and a better-matched measurement of patients' factual knowledge. These results suggest that physicians need to improve their ability to assess patient understanding of clinical trial information, in order to be able to tailor the patients' information individually.
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| 12. |
- Dellson, Pia, et al.
(författare)
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Patients' reasoning regarding the decision to participate in clinical cancer trials : an interview study
- 2018
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clinical cancer trials are crucial for the implementation of new treatments in the clinical setting, but it is equally crucial that patients are given the opportunity to make a well-informed decision about participation. The inclusion process is complex, including both oral and written information about the trial. The process of patients' decision-making regarding clinical cancer trials has not yet been sufficiently studied. This interview study aims to explore the process of patients' reasoning regarding the decision to participate in a clinical cancer trial.METHODS: The study is based on 27 individual face-to-face interviews with patients who had decided to participate in a clinical cancer trial. The interviews were audio-recorded and transcribed verbatim and then analysed using inductive content analysis.RESULTS: Content analysis revealed 17 subthemes grouped into five themes: (1) an unhesitating decision to participate; (2) a decision based on flimsy grounds and guided by emotion; (3) feeling safe and secure with my decision; (4) faced with a choice versus what choice do I have? and (5) hoping for help while helping others. The decision to participate in a clinical cancer trial was often immediate and guided by emotions, based on a trusting relationship with healthcare personnel rather than on careful reading of written information. Palliative patients, in particular, sometimes had unrealistic beliefs about the effectiveness of the trial treatment.CONCLUSIONS: It is vital that the decision to participate in a clinical cancer trial is preceded by an honest dialogue about possible positive and negative effects of the trial treatments, including other options such as supportive care in the palliative setting. Our findings also raise the questions of how important written information is for the decision-making process and also whether genuine informed consent is possible. To reach a higher degree of informed consent, it is most important that the oral information is given in a thorough and unbiased manner.
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| 13. |
- Dryver, ET, et al.
(författare)
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Follow-up of patients with Hodgkin's disease following curative treatment: the routine CT scan is of little value
- 2003
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 89:3, s. 482-486
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Tidskriftsartikel (refereegranskat)abstract
- A total of 10-40% of patients with Hodgkin's disease relapse following initial curative therapy. Intensive follow-up is resource intensive and may identify false relapses. We performed a retrospective review of all patients with Hodgkin's disease treated at our centre between 1990 and 1999 to evaluate the utility of the components of follow-up. A total of 107 patients met the inclusion and exclusion criteria. The median age was 33 years and the median duration of follow-up 38 months. The total number of follow-up visits was 1209 and total number of CT scans 283. There were 109 suspected relapses of which 22 proved to be true relapses. Of the latter, 14 were identified clinically, six radiologically and two via lab testing. The routine CT scan detected only two relapses (9%), yet accounted for 29% of the total follow-up costs. Based on data from our centre, the cost per true relapse was $6000 US, 49% incurred by radiological tests. The majority of the cost of follow-up was incurred by routine follow-up (84%) as opposed to the investigation of suspected relapses (16%). We conclude that most true relapses are clinically symptomatic and that the routine CT is an expensive and inefficient mode of routine follow-up.
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| 14. |
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| 15. |
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| 16. |
- Elebro, Karin, et al.
(författare)
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Androgen receptor expression and breast cancer mortality in a population-based prospective cohort
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; , s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The increase in clinical trials with androgen receptor (AR)-targeting drugs emphasizes the need of clarifying the role of AR expression in different breast cancer subtypes. AR confers good prognosis in estrogen receptor positive (ER+) breast cancer, but its role in ER-negative (ER−) breast cancer is unclear. The aim of this study was to elaborate on previous findings of a differential prognostic role for AR depending on ER status, using breast cancer mortality (BCM) as endpoint, in a population-based cohort from the Malmö Diet and Cancer Study. Methods: Immunohistochemical AR expression was assessed in 910 women with invasive breast cancer diagnosed 1991–2010, supplemented with clinicopathological information, vital status, and cause of death, with the last follow-up in December 2014 (median 10 years). Survival analyses according to AR status and AR/ER combinations were performed. Results: AR expression was available for 671 tumors. AR+ (n = 573, 85%) was associated with favorable established tumor markers and lower BCM in univariable analysis, especially during the first 5 years following diagnosis [HR 0.4; 95% confidence intervals (CI) 0.2–0.7]. Multivariable analysis for short-term follow-up indicated higher BCM among patients with AR+ER− tumors (HR 3.5; 95% CI 1.4–9.1) than other AR and ER combinations. Conclusions: AR expression added prognostic information to ER expression with respect to short-term prognosis. The worst prognosis was seen for patients with AR+/ER− tumors in short-term follow-up, supporting the pre-specified hypothesis. However, larger cohorts are needed for further characterization of the role of AR expression in ER− breast cancer.
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| 17. |
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| 18. |
- Elebro, Karin, et al.
(författare)
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High Estrogen Receptor β Expression Is Prognostic among Adjuvant Chemotherapy-Treated Patients-Results from a Population-Based Breast Cancer Cohort
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 23:3, s. 766-777
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Isoform-specific tumor estrogen receptor β (ERβ) expression may hold prognostic information in breast cancer, especially among endocrine-treated breast cancer patients. The study's purpose was to evaluate ERβ isoform 1 (ERβ1) expression in relation to tumor characteristics, ESR2 genotypes, and prognosis in different treatment groups.EXPERIMENTAL DESIGN: A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between October 2002 and June 2012 was followed until June 2014 (median 5 years). Associations between immunohistochemical ERβ1 expression, patient and tumor characteristics, as well as outcome within treatment groups were analyzed.RESULTS: Tumor ERβ1 expression was available for 911 patients (89%) and was not associated with ESR2 genotypes. ERβ1 positivity, defined as >75% (ERβ175(+), 72.7%), was positively associated with established favorable tumor characteristics. Overall, ERβ175(+) was associated with lower risk of breast cancer events [HRadj = 0.60; 95% confidence interval (CI), 0.41-0.89]. The magnitude of the association was larger in patients with ERα(-) tumors (HRadj = 0.30; 95% CI, 0.12-0.76), compared with ERα(+) tumors (HRadj = 0.66; 95% CI, 0.42-1.03). Among the 232 chemotherapy-treated patients, ERβ175(+) tumors were associated with lower risk of breast cancer events compared with ERβ175(-) tumors (HRadj = 0.31; 95% CI, 0.15-0.64). Among the 671 chemonaïve patients, ERβ175 status was not associated with the outcome.CONCLUSION: High ERβ1 expression was a favorable prognostic marker in this breast cancer cohort, especially in chemotherapy-treated patients, but not in endocrine therapy-treated patients. These results warrant confirmation, preferably via a biomarker study in a previously conducted randomized trial. Clin Cancer Res; 1-12. ©2016 AACR.
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| 21. |
- Elit, L, et al.
(författare)
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Familial and hormonal risk factors for papillary serous uterine cancer
- 2002
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Ingår i: European Journal of Gynaecological Oncology. - 0392-2936. ; 23:3, s. 187-190
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To identify genetic and non-genetic risk factors for papillary serous uterine cancer. Methods: A case-control study was conducted. Case women with papillary serous uterine cancer were compared with two control groups: 1) women with endometrioid uterine cancer and 2) healthy women with no past history of cancer. Cases and controls were matched for age (within two years) and ethnic group. All study subjects completed a questionnaire addressing family history. The cases and healthy controls were assessed for factors associated with estrogen exposure. Results: The risks of breast cancer (RR 1.84, Cl 1.03-331) and of prostate cancer (RR 2.21, CI 0.77-6.37) were higher among the relatives of patients with papillary serous uterine cancer, than among relatives of those with endometrioid uterine cancer. Other significant risk factors included weight at 18 years (p = 0.04) and the use of estrogen replacement therapy (p = 0.04). Conclusion: Relatives of women with papillary serous cancer of the uterus had an increased risk of breast and prostate cancer. Hormonal exposure also increases the risk for this cancer. These Findings suggest that predisposing genetic factors, possibly related to hormone metabolism, may be common to the three forms of cancer.
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| 22. |
- Ellberg, Carolina, et al.
(författare)
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Breast cancer and spider telangiectasias at diagnosis and its relation to histopathology and prognosis: a population-based study.
- 2012
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 131:1, s. 177-186
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis is one of the hallmarks of breast cancer. The status of angiogenesis is important in therapy choice. Spider telangiectasias (telangiectasias) may reflect an increased ability to form vessels. Our first aim was to identify patient and tumor characteristics associated with the occurrence of telangiectasias at the time of breast cancer diagnosis. The second aim was to study the overall survival in relation to the occurrence of telangiectasias at the time of breast cancer diagnosis. A standardized questionnaire was used to interview 1682 consecutive breast cancer patients about risk factors between 1980 and 2009. Occurrence of telangiectasias at the time of breast cancer diagnosis on the upper thorax, head, and/or neck was recorded by one physician. In the cohort, 93 women (5.5%) had telangiectasias. Occurrence of telangiectasias was positively associated with weight, odds ratio (OR) 1.02 (95% confidence interval (CI) 1.00-1.05) per kg, ever-use of oral contraceptives OR 2.67(CI 1.55-4.63) and hormone replacement therapy OR 2.68(CI 1.63-4.39), and negatively associated with parity OR 0.45(CI 0.25-0.79). Telangiectasias were not present in patients with comedo breast cancer. Patients with occurrences of telangiectasias diagnosed before the age of 50 had a statistically non-significant worse overall survival, whereas the patients with occurrences of telangiectasias diagnosed at age 50 or after had a statistically significant better overall survival (P interaction = 0.016). The relationship between the occurrence of telangiectasias and the overall survival in the older patient-group was independent of ever-use of HRT. Hormonal risk factors for breast cancer were associated with the occurrence of spider telangiectasias. The occurrence of telangiectasias may reflect the angiogenic status of the tumor. We hypothesize that telangiectasias could be used as selection criteria for anti-angiogenic therapy in younger breast cancer patients. Therefore, patients with comedo breast cancers maybe a group that may benefit less from anti-angiogenic therapy.
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| 23. |
- Ellberg, Carolina, et al.
(författare)
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Current smoking is associated with a larger waist circumference and a more androgenic profile in young healthy women from high-risk breast cancer families
- 2018
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 29:2, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- The purpose was to elucidate the interplay between current smoking, anthropometric measurements, and endogenous hormone levels in women ≤ 40 years. Questionnaires on lifestyle and reproductive factors were completed by 269 healthy women from high-risk breast cancer families between 1996 and 2006 in Sweden. Blood samples for analyses of plasma testosterone, estradiol, androstenedione, sex hormone-binding globulin, and body measurements were obtained 5–10 days before predicted onset of the next menstrual period. Women without smoking status, who were currently breastfeeding, or using hormonal contraception other than combined oral contraceptives (OCs) were excluded (n = 27). Current smokers (n = 57) had larger waist circumference (adjp = 0.004) and waist-to-hip ratio (WHR) (adjp = 0.007) than non-smokers (n = 185). In non-OC users, adjusted mean androstenedione levels were higher in current smokers compared with non-smokers (10.3 vs. 8.6 nmol/L; adjp = 0.0002). While in current OC users estradiol levels were higher in smokers compared with non-smokers (22.5 vs. 17.4 pg/mL; adjp = 0.012). In multivariable models, WHR was associated with both current smoking (adjp ≤ 0.016) and higher levels of androstenedione (adjp = 0.05) or bioavailable testosterone (adjp = 0.001). Among non-OC users, a more androgenic profile was observed in current smokers compared with non-smokers, but not in current OC users. Irrespective of OC use, current smoking was associated with increased waist circumference.
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| 24. |
- Ellberg, Carolina, et al.
(författare)
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Impact of a paternal origin of germline BRCA1/2 mutations on the age at breast and ovarian cancer diagnosis in a Southern Swedish cohort.
- 2015
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 54:1, s. 39-50
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Tidskriftsartikel (refereegranskat)abstract
- Three studies have reported that BRCA1/2 mutations of paternal origin confer an earlier age at breast cancer diagnosis compared with maternal origin. The primary aim of this study was to investigate the impact of parental origin of BRCA1/2 mutations on age at breast and ovarian cancer diagnosis. This study included 577 female BRCA1/2 mutation carriers. All BRCA1/2 mutation carriers belonged to families registered between 1993 and 2011 at the Oncogenetic Clinic at Skånes University Hospital, Lund, Sweden. Cox proportional hazard ratios were used to analyze time to breast or ovarian cancer diagnosis. A novel finding was that carriers of BRCA1 mutations of paternal origin were 4 years older at age of ovarian cancer (P = 0.009) compared with those carrying a BRCA1 mutation of maternal origin. BRCA1 carriers with mutations of paternal origin were 4 years younger at breast cancer diagnosis (P = 0.017) compared with those carrying a BRCA1 mutation of maternal origin, which is in agreement with three previous studies. Both findings were adjusted for of year of inclusion, birth date, and oral contraceptive pill use. No associations between parental origin of BRCA2 mutations and time to breast or ovarian cancer diagnosis were found. An attempt to handle a potential selection bias regarding use of oral contraceptives was made using multiple imputations by chained equations. The observed age difference may allow a greater understanding of mechanisms associated with the differences in cancer penetrance in BRCA1/2 mutation carriers, some of which may depend on paternal origin. © 2014 Wiley Periodicals, Inc.
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| 25. |
- Godina, Christopher, et al.
(författare)
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Caveolin-1 gene expression provides additional prognostic information combined with PAM50 risk of recurrence (ROR) score in breast cancer
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Combining information from the tumor microenvironment (TME) with PAM50 Risk of Recurrence (ROR) score could improve breast cancer prognostication. Caveolin-1 (CAV1) is a marker of an active TME. CAV1 is a membrane protein involved in cell signaling, extracellular matrix organization, and tumor-stroma interactions. We sought to investigate CAV1 gene expression in relation to PAM50 subtypes, ROR score, and their joint prognostic impact. CAV1 expression was compared between PAM50 subtypes and ROR categories in two cohorts (SCAN-B, n = 5326 and METABRIC, n = 1980). CAV1 expression was assessed in relation to clinical outcomes using Cox regression and adjusted for clinicopathological predictors. Effect modifications between CAV1 expression and ROR categories on clinical outcome were investigated using multiplicative and additive two-way interaction analyses. Differential gene expression and gene set enrichment analyses were applied to compare high and low expressing CAV1 tumors. All samples expressed CAV1 with the highest expression in the Normal-like subtype. Gene modules consistent with epithelial-mesenchymal transition (EMT), hypoxia, and stromal activation were associated with high CAV1 expression. CAV1 expression was inversely associated with ROR category. Interactions between CAV1 expression and ROR categories were observed in both cohorts. High expressing CAV1 tumors conferred worse prognosis only within the group classified as ROR high. ROR gave markedly different prognostic information depending on the underlying CAV1 expression. CAV1, a potential mediator between the malignant cells and TME, could be a useful biomarker that enhances and further refines PAM50 ROR risk stratification in patients with ROR high tumors and a potential therapeutic target.
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