| 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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| 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. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- Godina, Christopher, et al.
(författare)
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High Caveolin-1 mRNA expression in triple-negative breast cancer is associated with an aggressive tumor microenvironment, chemoresistance, and poor clinical outcome
- 2024
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:7, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Currently, there are few treatment-predictive and prognostic biomarkers in triple-negative breast cancer (TNBC). Caveolin-1 (CAV1) is linked to chemoresistance and several important processes involved in tumor progression and metastasis, such as epithelial-mesenchymal transition (EMT). Herein, we report that high CAV1 gene expression is an independent factor of poor prognosis in TNBC.METHODS: CAV1 gene expression was compared across different molecular features (e.g., PAM50 subtypes). CAV1 expression was assessed in relation to clinical outcomes using Cox regression adjusted for clinicopathological predictors. Differential gene expression and gene set enrichment analyses were applied to compare high- and low-expressing CAV1 tumors. Tumor microenvironment composition of high- and low-expressing CAV1 tumors was estimated using ECOTYPER. Tumor tissue microarrays were used to evaluate CAV1 protein levels in stromal and malignant cells.RESULTS: In the SCAN-B (n = 525) and GSE31519 (n = 327) cohorts, patients with CAV1-high tumors had an increased incidence of early recurrence adjusted HR 1.78 (95% CI 1.12-2.81) and 2.20 (95% CI 1.39-3.47), respectively. In further analysis, high CAV1 gene expression was associated with a molecular profile indicating altered metabolism, neovascularization, chemoresistance, EMT, suppressed immune response, and active tumor microenvironment. Protein levels of CAV1 in malignant and stromal cells were not correlated with CAV1 gene expression.CONCLUSION: CAV1 gene expression in TNBC is a biomarker that merits further investigation in clinical trials and as a therapeutic target.
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| 9. |
- Godina, Christopher, et al.
(författare)
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Interplay between Caveolin-1 and body and tumor size affects clinical outcomes in breast cancer
- 2022
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Ingår i: Translational Oncology. - : Elsevier. - 1944-7124 .- 1936-5233. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Caveolin-1 (CAV1) is associated with cholesterol-rich membrane raft domains and is a master regulator of cell signaling and membrane transport. Here, we investigated CAV1's role in cellular compartments of breast cancer in relation to signaling pathways, clinicopathological features, and clinical outcomes.Methods: CAV1 levels were evaluated with immunohistochemistry in cytoplasm of invasive tumor cells and stromal cells in tumor tissue microarrays from a cohort of 1018 breast cancer patients (inclusion 2002-2012, Sweden). Cytoplasmic and stromal CAV1 were categorized as positive/negative and strong/not strong, respectively. CAV1 expression in relation to clinical outcomes was assessed with Cox regression. Investigations into CAV1 functional pathways was conducted in the STRING, GOBO, and TCGA databases.Results: CAV1 expression was associated with non-luminal subtypes, cell cycle control, inflammation, epithelialmesenchymal transition, and the IGF/Insulin system. Generally, CAV1 was not associated with recurrence risk. Stromal CAV1's impact on recurrence risk was modified by BMI > 25 kg/m(2) (P-interaction = 0.002), waist > 80 cm (P-interaction = 0.005), and invasive tumor size (pT2/3/4) (P-interaction = 0.028). In low-risk patients only, strong stromal CAV1 significantly increased recurrence risk (HRs(adj) > 1.61). In all patients, positive cytoplasmic CAV1 conferred > 2-fold risk for contralateral disease HRadj 2.63 (95% CI 1.36-5.10). Strong stromal CAV1 conferred nearly 2-fold risk for locoregional recurrence HRadj 1.88 (95% CI 1.09-3.24).Conclusions: CAV1's prognostic impact depended on its localization, anthropometric, and tumor factors. Stromal CAV1 predicted high recurrence risk in a group of supposedly "low-risk' patients. Cytoplasmic CAV1 predicted metachronous contralateral disease. If confirmed, CAV1 could be used as treatment target and for risk stratification.
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| 10. |
- Gustbée, Emma, et al.
(författare)
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Excessive milk production during breast-feeding prior to breast cancer diagnosis is associated with increased risk for early events.
- 2013
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Ingår i: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Breast-feeding is a known protective factor against breast cancer. Breast-feeding duration is influenced by hormone levels, milk production, and lifestyle factors. The aims were to investigate how breast-feeding duration and milk production affected tumor characteristics and risk for early breast cancer events in primary breast cancer patients. Between 2002 and 2008, 634 breast cancer patients in Lund, Sweden, took part in an ongoing prospective cohort study. Data were extracted from questionnaires, pathology reports, and patients' charts from 592 patients without preoperative treatment. Breast-feeding duration ≤12 months of the first child was associated with higher frequency of ER+/PgR+ tumors (P=0.02). Median follow-up time was 4.9 years. Higher risk for early events was observed for breast-feeding duration of first child >12 months (LogRank P=0.001), total breast-feeding duration >12 months (LogRank P=0.008), as well as 'excessive milk production' during breast-feeding of the first child (LogRank P=0.001). Patients with 'almost no milk production' had no events. In a multivariable model including both 'excessive milk production' and breast-feeding duration of the first child >12 months, both were associated with a two-fold risk for early events, adjusted HRs 2.33 (95% CI: 1.25-4.36) and 2.39 (0.97-5.85), respectively, while total breast-feeding duration was not. 'Excessive milk production' was associated with a two-fold risk of early distant metastases, adjusted HR 2.59 (1.13-5.94), but not duration. In conclusion, 'excessive milk production' during breast-feeding was associated with higher risk for early events independent of tumor characteristics, stressing the need to consider host factors in the evaluation of prognostic markers.
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