| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- Carlsson, Anders, et al.
(författare)
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Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases.
- 2011
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 108:34, s. 14252-14257
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Tidskriftsartikel (refereegranskat)abstract
- The risk of distant recurrence in breast cancer patients is difficult to assess with current clinical and histopathological parameters, and no validated serum biomarkers currently exist. Using a recently developed recombinant antibody microarray platform containing 135 antibodies against 65 mainly immunoregulatory proteins, we screened 240 sera from 64 patients with primary breast cancer. This unique longitudinal sample material was collected from each patient between 0 and 36 mo after the primary operation. The velocity for each serum protein was determined by comparing the samples collected at the primary operation and then 3-6 mo later. A 21-protein signature was identified, using leave-one-out cross-validation together with a backward elimination strategy in a training cohort. This signature was tested and evaluated subsequently in an independent test cohort (prevalidation). The risk of developing distant recurrence after primary operation could be assessed for each patient, using her molecular portraits. The results from this prevalidation study showed that patients could be classified into high- versus low-risk groups for developing metastatic breast cancer with a receiver operating characteristic area under the curve of 0.85. This risk assessment was not dependent on the type of adjuvant therapy received by the patients. Even more importantly, we demonstrated that this protein signature provided an added value compared with conventional clinical parameters. Consequently, we present here a candidate serum biomarker signature able to classify patients with primary breast cancer according to their risk of developing distant recurrence, with an accuracy outperforming current procedures.
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| 8. |
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| 9. |
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| 10. |
- 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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