| 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. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
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| 9. |
- 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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