Blood Gene Expression Profiling of Breast Cancer Survivors Experiencing Fibrosis

Landmark-Høyvik, Hege; Dumeaux, Vanessa; Reinertsen, Kristin V.; Edvardsen, Hege; Fosså, Sophie D.; Børresen‐Dale, Anne‐Lise

doi:10.1016/j.ijrobp.2010.09.052

Cited by 12 publications

(6 citation statements)

References 41 publications

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“…However it seems possible that the RT-techniques used in the two patient groups were associated with relatively high risks of developing late fibrosis so that only resistant patients would stand out whereas patients with average sensitivity would develop fibrosis due to treatment-related factors. Recently, a gene expression profile for late fibrosis was derived in unirradiated blood cells from 254 women treated with breast conserving therapy, 31 of whom developed fibrosis 3-7 years after RT (157). Eighty-seven differentially expressed genes included functions in transcription, intracellular transport and localisation, and development, with down-regulation of most genes but up-regulation of SERPINE1 (coding for plasminogen activator inhibitor-1), in accordance with increased protein levels found in fibrotic conditions (158).…”

Section: ‘Omics’ Approachesmentioning

confidence: 99%

“…Eighty-seven differentially expressed genes included functions in transcription, intracellular transport and localisation, and development, with down-regulation of most genes but up-regulation of SERPINE1 (coding for plasminogen activator inhibitor-1), in accordance with increased protein levels found in fibrotic conditions (158). Pathway analysis identified the TGF-β1 signalling and interleukin-2 pathways as the two major gene sets (157). Independent replication of these results will be needed and validation in rigorous prospective trials.…”

Section: ‘Omics’ Approachesmentioning

confidence: 99%

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Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

et al. 2016

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Adverse reactions in normal tissue after radiotherapy (RT) limit the dose that can be given to tumour cells. Since 80% of individual variation in clinical response is estimated to be caused by patient-related factors, identifying these factors might allow prediction of patients with increased risk of developing severe reactions. While inactivation of cell renewal is considered a major cause of toxicity in early-reacting normal tissues, complex interactions involving multiple cell types, cytokines, and hypoxia seem important for late reactions. Here, we review ‘omics’ approaches such as screening of genetic polymorphisms or gene expression analysis, and assess the potential of epigenetic factors, posttranslational modification, signal transduction, and metabolism. Furthermore, functional assays have suggested possible associations with clinical risk of adverse reaction. Pathway analysis incorporating different ‘omics’ approaches may be more efficient in identifying critical pathways than pathway analysis based on single ‘omics’ data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of RT patients characterized by different mechanisms. Thus ‘omics’ and functional approaches may synergize if they are integrated into radiogenomics ‘systems biology’ to facilitate the goal of individualised radiotherapy.

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Section: ‘Omics’ Approachesmentioning

confidence: 99%

Section: ‘Omics’ Approachesmentioning

confidence: 99%

Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

et al. 2016

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“…Following radiotherapy for breast cancer, gene expression changes at mRNA level can be detected in samples taken months or years after the treatment course in blood from patients with established breast fibrosis [6], and in breast tissue [7]. Genes identified in these studies include those encoding pro-inflammatory and pro-fibrotic cytokines.…”

Section: Introductionmentioning

confidence: 99%

Cytokine levels as biomarkers of radiation fibrosis in patients treated with breast radiotherapy

et al. 2014

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BackgroundRadiation fibrosis is not easily measurable although clinical scores have been developed for this purpose. Biomarkers present an alternative more objective approach to quantification, and estimation in blood provides accessible samples. We investigated if blood cytokines could be used to measure established fibrosis in patients who have undergone radiotherapy for breast cancer.MethodsWe studied two cohorts treated by breast-conserving surgery and radiotherapy in the UK START Trial A, one with breast fibrosis (cases) and one with no or minimal fibrosis (controls). Two candidate cytokines, plasma connective tissue growth factor (CTGF) and serum interleukin-6 (IL6) were estimated by ELISA. Comparisons between cases and controls used the t-test or Mann–Whitney test and associations between blood concentration and clinical factors were assessed using the Spearman rank correlation coefficient.ResultsSeventy patients were included (26 cases, 44 controls). Mean time since radiotherapy was 9.9 years (range 8.3-12.0). No statistically significant differences between cases and controls in serum IL6 (median (IQR) 0.84 pg/ml (0.57-1.14), 0.75 pg/ml (0.41-1.43) respectively) or plasma CTGF (331.4 pg/ml (234.8-602.9), 334.5 pg/ml (270.0-452.8) were identified. There were no significant associations between blood cytokine concentration and age, fibrosis severity, breast size or time since radiotherapy.ConclusionsNo significant difference in IL6 or CTGF concentrations was detected between patients with breast fibrosis and controls with minimal or no fibrosis.

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“…These changes are the result of pro-inflammatory and pro-fibrotic cytokines such as transforming growth factor (TGF)-β1 released during the initiating phase of RIF development (11, 12). During the chronic phase of RIF there is actually deregulation of fibrinolysis with diminished ECM break-down, resulting in the maintenance of the overabundant fibrous tissue (13). However, there is great variability in whether or not a patient experiences RIF following breast irradiation (14).…”

Section: Introductionmentioning

confidence: 99%

Transforming Growth Factor β-1 (TGF-β1) Is a Serum Biomarker of Radiation Induced Fibrosis in Patients Treated With Intracavitary Accelerated Partial Breast Irradiation: Preliminary Results of a Prospective Study

Boothe

Coplowitz

Greenwood

et al. 2013

International Journal of Radiation Oncology*Biology*Physics

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Purpose To examine a relationship between serum transforming growth factor beta-1 (TGF-β1) values and radiation induced fibrosis (RIF). Methods We conducted a prospective analysis of development of RIF in 38 women with AJCC Stage 0-I breast cancer treated with lumpectomy and accelerated partial breast irradiation via interstitial brachytherapy (IBAPBI). An ELISA (Quantikine ®, R&D, MN) immunoassay was used to measure serum TGF-β1 pre-surgery, pre- IBAPBI, and during IBAPBI. Blood samples for TGF-β1 were also collected from 15 healthy, non-treated women (controls). The previously validated tissue compliance meter (TCM) was used to objectively assess radiation-induced fibrosis (RIF). Results Median time to follow-up for 38 patients is 44 months (range, 5 – 59 months). RIF is graded by the TCM scale as 0, 1, 2 and 3 in 5/20 (25%), 6/20 (30%), 5/20 (25%) and 4/20 (20%) patients, respectively. ΔTCM ≥6mm (moderate-to-severe RIF) is statistically different from ΔTCM ≤3mm (none-to-mild RIF) (p<0.05). Mean serum TGF-β1 values are significantly higher in patients pre-surgery than disease-free controls in: a) all cancer patients (30,201 ± 5,889 pg/ml, p=0.02), b) patients with any type of RIF (32,273 ± 5,016 pg/ml, p<0.0001) and c) women with moderate-to-severe RIF (34,462 ± 4,713 pg/ml, p<0.0001). The post-IBAPBI mean serum TGF-β1 is 21,915pg/ml in patients with ΔTCM ≥6mm (moderate-severe RIF). This is significantly higher than the mean serum TGF-β1, 14,940pg/ml, in patients with ΔTCM ≤3mm (p = 0.036). In patients who develop moderate-to-severe RIF, pre-IAPBI mean TGF-β1 values are also predictive of this sequela (17,885 ± 3,952 pg/ml, p=0.007). Conclusions TGF-β1 levels correlate with development of moderate-to-severe RIF. The pre-IBAPBI mean TGF-β1 levels can serve as an early biomarker for development of moderate-to-severe RIF after IBAPBI

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Blood Gene Expression Profiling of Breast Cancer Survivors Experiencing Fibrosis

Cited by 12 publications

References 41 publications

Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?

Cytokine levels as biomarkers of radiation fibrosis in patients treated with breast radiotherapy

Transforming Growth Factor β-1 (TGF-β1) Is a Serum Biomarker of Radiation Induced Fibrosis in Patients Treated With Intracavitary Accelerated Partial Breast Irradiation: Preliminary Results of a Prospective Study

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