{"entity": "journal", "iuid": "05f8e04acc9544f0ac28f5141b64c2ae", "timestamp": "2026-07-17T07:49:27.170Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Breast%20Cancer%20Res..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Breast%20Cancer%20Res."}}, "title": "Breast Cancer Res.", "issn": "1465-542X", "issn-l": "1465-5411", "publications_count": 9, "publications": [{"entity": "publication", "iuid": "f99abb60556e417282a30affe3cdf0a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f99abb60556e417282a30affe3cdf0a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f99abb60556e417282a30affe3cdf0a1"}}, "title": "Polygenic scores in Familial breast cancer cases with and without pathogenic variants and the risk of contralateral breast cancer.", "authors": [{"family": "Kvist", "given": "Anders", "initials": "A"}, {"family": "K\u00e4mpe", "given": "Anders", "initials": "A"}, {"family": "T\u00f6rngren", "given": "Therese", "initials": "T"}, {"family": "Tesi", "given": "Bianca", "initials": "B"}, {"family": "Baliakas", "given": "Panagiotis", "initials": "P"}, {"family": "Borg", "given": "\u00c5ke", "initials": "\u00c5"}, {"family": "Eriksson", "given": "Daniel", "initials": "D"}], "type": "journal article", "published": "2025-09-08", "journal": {"title": "Breast Cancer Res.", "issn": "1465-542X", "volume": "27", "issue": "1", "pages": "160", "issn-l": "1465-5411"}, "abstract": "Polygenic risk scores (PRS) are not yet standard in clinical risk assessments for familial breast cancer in Sweden. This study evaluated the distribution and impact of an established PRS (PRS313) in women undergoing clinical sequencing for hereditary breast cancer.\n\nWe integrated PRS313 into a hereditary breast cancer gene panel used in clinical practice and calculated scores for 262 women. Comparisons were made between women with unilateral and contralateral breast cancer, as well as those with and without pathogenic variants in breast cancer susceptibility genes. PRS313 was significantly higher in women with contralateral breast cancer (median + 1.3 SD, n = 33, P = 8e-9) compared to those with unilateral disease (median + 0.66 SD, n = 197, P = 5e-10). Elevated PRS313 was also observed in women with pathogenic variants, including those in high-penetrance genes (+ 0.65 SD) and moderate-penetrance genes (+ 0.93 SD), compared to population controls. Incorporating PRS313 into a clinical risk model (BOADICEA), shifted 20%-27% of women with moderate-penetrance variants and 23%-32% of women without pathogenic variants into different risk categories according to NCCN and NICE guidelines.\n\nWomen with familial breast cancer showed elevated PRS313, including those with pathogenic variants, contributing to the observed high risk in these families. Integrating PRS into risk assessment and genetic counselling has the potential to refine risk predictions, even among women with breast cancer attributed to monogenic variants.", "doi": "10.1186/s13058-025-02107-5", "pmid": "40922009", "labels": {"Clinical Genomics Uppsala": "Service", "Clinical Genomics": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12418628"}, {"db": "pii", "key": "10.1186/s13058-025-02107-5"}], "notes": [], "created": "2025-11-26T14:14:01.393Z", "modified": "2025-11-28T10:53:05.161Z"}, {"entity": "publication", "iuid": "9b5552f6ed314a64a3613c88047c30d0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9b5552f6ed314a64a3613c88047c30d0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9b5552f6ed314a64a3613c88047c30d0"}}, "title": "Identification of a Notch transcriptomic signature for breast cancer.", "authors": [{"family": "Braune", "given": "Eike-Benjamin", "initials": "EB"}, {"family": "Geist", "given": "Felix", "initials": "F"}, {"family": "Tang", "given": "Xiaojia", "initials": "X"}, {"family": "Kalari", "given": "Krishna", "initials": "K"}, {"family": "Boughey", "given": "Judy", "initials": "J"}, {"family": "Wang", "given": "Liewei", "initials": "L"}, {"family": "Leon-Ferre", "given": "Roberto A", "initials": "RA"}, {"family": "D'Assoro", "given": "Antonino B", "initials": "AB"}, {"family": "Ingle", "given": "James N", "initials": "JN"}, {"family": "Goetz", "given": "Matthew P", "initials": "MP"}, {"family": "Kreis", "given": "Julian", "initials": "J"}, {"family": "Wang", "given": "Kang", "initials": "K"}, {"family": "Foukakis", "given": "Theodoros", "initials": "T"}, {"family": "Seshire", "given": "Anita", "initials": "A"}, {"family": "Wienke", "given": "Dirk", "initials": "D"}, {"family": "Lendahl", "given": "Urban", "initials": "U"}], "type": "journal article", "published": "2024-01-03", "journal": {"title": "Breast Cancer Res.", "issn": "1465-542X", "volume": "26", "issue": "1", "pages": "4", "issn-l": "1465-5411"}, "abstract": "Dysregulated Notch signalling contributes to breast cancer development and progression, but validated tools to measure the level of Notch signalling in breast cancer subtypes and in response to systemic therapy are largely lacking. A transcriptomic signature of Notch signalling would be warranted, for example to monitor the effects of future Notch-targeting therapies and to learn whether altered Notch signalling is an off-target effect of current breast cancer therapies. In this report, we have established such a classifier.\n\nTo generate the signature, we first identified Notch-regulated genes from six basal-like breast cancer cell lines subjected to elevated or reduced Notch signalling by culturing on immobilized Notch ligand Jagged1 or blockade of Notch by \u03b3-secretase inhibitors, respectively. From this cadre of Notch-regulated genes, we developed candidate transcriptomic signatures that were trained on a breast cancer patient dataset (the TCGA-BRCA cohort) and a broader breast cancer cell line cohort and sought to validate in independent datasets.\n\nAn optimal 20-gene transcriptomic signature was selected. We validated the signature on two independent patient datasets (METABRIC and Oslo2), and it showed an improved coherence score and tumour specificity compared with previously published signatures. Furthermore, the signature score was particularly high for basal-like breast cancer, indicating an enhanced level of Notch signalling in this subtype. The signature score was increased after neoadjuvant treatment in the PROMIX and BEAUTY patient cohorts, and a lower signature score generally correlated with better clinical outcome.\n\nThe 20-gene transcriptional signature will be a valuable tool to evaluate the response of future Notch-targeting therapies for breast cancer, to learn about potential effects on Notch signalling from conventional breast cancer therapies and to better stratify patients for therapy considerations.", "doi": "10.1186/s13058-023-01757-7", "pmid": "38172915", "labels": {"NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10765899"}, {"db": "pii", "key": "10.1186/s13058-023-01757-7"}], "notes": [], "created": "2024-03-14T11:19:34.094Z", "modified": "2024-03-14T11:20:32.303Z"}, {"entity": "publication", "iuid": "b497203a64f24a21b4e18fc5c671604c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b497203a64f24a21b4e18fc5c671604c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b497203a64f24a21b4e18fc5c671604c"}}, "title": "Serum immuno-oncology markers carry independent prognostic information in patients with newly diagnosed metastatic breast cancer, from a prospective observational study.", "authors": [{"family": "Gunnarsdottir", "given": "Frida Bj\u00f6rk", "initials": "FB"}, {"family": "Bendahl", "given": "P\u00e4r-Ola", "initials": "PO"}, {"family": "Johansson", "given": "Alexandra", "initials": "A"}, {"family": "Benfeitas", "given": "Rui", "initials": "R"}, {"family": "Ryd\u00e9n", "given": "Lisa", "initials": "L"}, {"family": "Bergenfelz", "given": "Caroline", "initials": "C"}, {"family": "Larsson", "given": "Anna-Maria", "initials": "AM"}], "type": "observational study", "published": "2023-03-21", "journal": {"title": "Breast Cancer Res.", "issn": "1465-542X", "volume": "25", "issue": "1", "pages": "29", "issn-l": "1465-5411"}, "abstract": "Metastatic breast cancer (MBC) is a challenging disease, and despite new therapies, prognosis is still poor for a majority of patients. There is a clinical need for improved prognostication where immuno-oncology markers can provide important information. The aim of this study was to evaluate serum immuno-oncology markers in MBC patients and their respective relevance for prediction of survival.\n\nWe investigated a broad panel of 92 immuno-oncology proteins in serum from 136 MBC patients included in a prospective observational study (NCT01322893) with long-term follow-up. Serum samples were collected before start of systemic therapy and analyzed using multiplex proximity extension assay (Olink Target 96 Immuno-Oncology panel). Multiple machine learning techniques were used to identify serum markers with highest importance for prediction of overall and progression-free survival (OS and PFS), and associations to survival were further evaluated using Cox regression analyses. False discovery rate was then used to adjust for multiple comparisons.\n\nUsing random forest and random survival forest analyses, we identified the top nine and ten variables of highest predictive importance for OS and PFS, respectively. Cox regression analyses revealed significant associations (P < 0.005) of higher serum levels of IL-8, IL-10 and CAIX with worse OS in multivariable analyses, adjusted for established clinical prognostic factors including circulating tumor cells (CTCs). Similarly, high serum levels of IL-8, IL-10, ADA and CASP8 significantly associated with worse PFS. Interestingly, high serum levels of FasL significantly associated with improved OS and PFS. In addition, CSF-1, IL-6, MUC16, TFNSFR4 and CD244 showed suggestive evidence (P < 0.05) for an association to survival in multivariable analyses. After correction for multiple comparisons, IL-8 still showed strong evidence for correlation to survival.\n\nTo conclude, we found six serum immuno-oncology markers that were significantly associated with OS and/or PFS in MBC patients, independently of other established prognostic factors including CTCs. Furthermore, an additional five serum immuno-oncology markers provided suggestive evidence for an independent association to survival. These findings highlight the relevance of immuno-oncology serum markers in MBC patients and support their usefulness for improved prognostication. Trial registration Clinical Trials (NCT01322893), registered March 25, 2011.", "doi": "10.1186/s13058-023-01631-6", "pmid": "36945037", "labels": {"Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10031935"}, {"db": "pii", "key": "10.1186/s13058-023-01631-6"}, {"db": "ClinicalTrials.gov", "key": "NCT01322893"}], "notes": [], "created": "2023-04-12T12:40:50.720Z", "modified": "2023-04-12T12:40:50.722Z"}, {"entity": "publication", "iuid": "f79fa2a53031442688d1bdad0d4b79da", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f79fa2a53031442688d1bdad0d4b79da.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f79fa2a53031442688d1bdad0d4b79da"}}, "title": "Distinct mechanisms of resistance to fulvestrant treatment dictate level of ER independence and selective response to CDK inhibitors in metastatic breast cancer.", "authors": [{"family": "Kaminska", "given": "Kamila", "initials": "K"}, {"family": "Akrap", "given": "Nina", "initials": "N"}, {"family": "Staaf", "given": "Johan", "initials": "J"}, {"family": "Alves", "given": "Carla L", "initials": "CL"}, {"family": "Ehinger", "given": "Anna", "initials": "A"}, {"family": "Ebbesson", "given": "Anna", "initials": "A"}, {"family": "Hedenfalk", "given": "Ingrid", "initials": "I"}, {"family": "Beumers", "given": "Lukas", "initials": "L"}, {"family": "Veerla", "given": "Srinivas", "initials": "S"}, {"family": "Harbst", "given": "Katja", "initials": "K"}, {"family": "Ehmsen", "given": "Sidse", "initials": "S"}, {"family": "Borgquist", "given": "Signe", "initials": "S"}, {"family": "Borg", "given": "\u00c5ke", "initials": "\u00c5"}, {"family": "P\u00e9rez-Fidalgo", "given": "Alejandro", "initials": "A"}, {"family": "Ditzel", "given": "Henrik J", "initials": "HJ"}, {"family": "Bosch", "given": "Ana", "initials": "A"}, {"family": "Honeth", "given": "Gabriella", "initials": "G", "orcid": "0000-0001-8086-2409", "researcher": {"href": "https://publications.scilifelab.se/researcher/bba95349161f4d6db290d589f2b06681.json"}}], "type": "journal article", "published": "2021-02-18", "journal": {"title": "Breast Cancer Res.", "issn": "1465-542X", "issn-l": "1465-5411", "volume": "23", "issue": "1", "pages": "26"}, "abstract": "Resistance to endocrine treatment in metastatic breast cancer is a major clinical challenge. Clinical tools to predict both drug resistance and possible treatment combination approaches to overcome it are lacking. This unmet need is mainly due to the heterogeneity underlying both the mechanisms involved in resistance development and breast cancer itself.\r\n\r\nTo study the complexity of the mechanisms involved in the resistance to the selective estrogen receptor degrader (SERD) fulvestrant, we performed comprehensive biomarker analyses using several in vitro models that recapitulate the heterogeneity of developed resistance. We further corroborated our findings in tissue samples from patients treated with fulvestrant.\r\n\r\nWe found that different in vitro models of fulvestrant resistance show variable stability in their phenotypes, which corresponded with distinct genomic alterations. Notably, the studied models presented adaptation at different cell cycle nodes to facilitate progression through the cell cycle and responded differently to CDK inhibitors. Cyclin E2 overexpression was identified as a biomarker of a persistent fulvestrant-resistant phenotype. Comparison of pre- and post-treatment paired tumor biopsies from patients treated with fulvestrant revealed an upregulation of cyclin E2 upon development of resistance. Moreover, overexpression of this cyclin was found to be a prognostic factor determining resistance to fulvestrant and shorter progression-free survival.\r\n\r\nThese data highlight the complexity of estrogen receptor positive breast cancer and suggest that the development of diverse resistance mechanisms dictate levels of ER independence and potentially cross-resistance to CDK inhibitors.", "doi": "10.1186/s13058-021-01402-1", "pmid": "33602273", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13058-021-01402-1"}, {"db": "pmc", "key": "PMC7893923"}], "notes": [], "created": "2021-11-23T13:34:59.914Z", "modified": "2021-12-09T13:42:28.368Z"}, {"entity": "publication", "iuid": "c96afccb586a4170b645b616dc18405c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c96afccb586a4170b645b616dc18405c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c96afccb586a4170b645b616dc18405c"}}, "title": "Clonal relatedness in tumour pairs of breast cancer patients.", "authors": [{"family": "Biermann", "given": "Jana", "initials": "J"}, {"family": "Parris", "given": "Toshima Z", "initials": "TZ"}, {"family": "Nemes", "given": "Szil\u00e1rd", "initials": "S"}, {"family": "Danielsson", "given": "Anna", "initials": "A"}, {"family": "Engqvist", "given": "Hanna", "initials": "H"}, {"family": "Werner R\u00f6nnerman", "given": "Elisabeth", "initials": "E"}, {"family": "Forssell-Aronsson", "given": "Eva", "initials": "E"}, {"family": "Kov\u00e1cs", "given": "Anik\u00f3", "initials": "A"}, {"family": "Karlsson", "given": "Per", "initials": "P"}, {"family": "Helou", "given": "Khalil", "initials": "K"}], "type": "journal article", "published": "2018-08-09", "journal": {"volume": "20", "issn": "1465-542X", "issue": "1", "pages": "96", "title": "Breast Cancer Res.", "issn-l": "1465-5411"}, "abstract": "Molecular classification of tumour clonality is currently not evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. There is no consensus about which type of data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours.\r\n\r\nThirty-seven invasive breast tumour pairs were stratified according to laterality and time interval between the diagnoses of the two tumours. In a multi-omics approach, tumour clonality was analysed by integrating clinical characteristics (n\u00a0=\u200937), DNA copy number (n\u2009=\u200937), DNA methylation (n\u00a0=\u20098), gene expression microarray (n\u00a0=\u20097), RNA sequencing (n\u2009=\u20093), and SNP genotyping data (n\u2009=\u20093). Different statistical methods, e.g. the diagnostic similarity index (SI), were used to classify the tumours as clonally related recurrences or independent primary tumours.\r\n\r\nThe SI and hierarchical clustering showed similar tendencies and the highest concordance with the other methods. Concordant evidence for tumour clonality was found in 46% (17/37) of patients. Notably, no association was found between the current clinical guidelines and molecular tumour features.\r\n\r\nA more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. Guidelines need to be defined with exact thresholds to standardise clonality testing in a routine diagnostic setting.", "doi": "10.1186/s13058-018-1022-y", "pmid": "30092821", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13058-018-1022-y"}, {"db": "GEO", "description": "Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas", "key": "GSE97293"}, {"db": "GEO", "description": "Genome-wide multi-omics profiling reveals extensive genetic complexity in 8p11-p12 amplified breast carcinomas [expression]", "key": "GSE97177"}], "notes": [], "created": "2018-08-16T15:30:10.983Z", "modified": "2024-01-16T13:48:45.779Z"}, {"entity": "publication", "iuid": "6ad7359492824600bfadb8deddc0e1c5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6ad7359492824600bfadb8deddc0e1c5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6ad7359492824600bfadb8deddc0e1c5"}}, "title": "Affinity proteomic profiling of plasma for proteins associated to area-based mammographic breast density.", "authors": [{"family": "Bystr\u00f6m", "given": "Sanna", "initials": "S"}, {"family": "Eklund", "given": "Martin", "initials": "M"}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG"}, {"family": "Fredolini", "given": "Claudia", "initials": "C", "orcid": "0000-0002-7674-2014", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ac3a5823cb4f998cc8bdb96dcbf195.json"}}, {"family": "Eriksson", "given": "Mikael", "initials": "M"}, {"family": "Czene", "given": "Kamila", "initials": "K"}, {"family": "Hall", "given": "Per", "initials": "P"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Gabrielson", "given": "Marike", "initials": "M"}], "type": "journal article", "published": "2018-02-14", "journal": {"volume": "20", "issn": "1465-542X", "issue": "1", "pages": "14", "title": "Breast Cancer Res.", "issn-l": "1465-5411"}, "abstract": "Mammographic breast density is one of the strongest risk factors for breast cancer, but molecular understanding of how breast density relates to cancer risk is less complete. Studies of proteins in blood plasma, possibly associated with mammographic density, are well-suited as these allow large-scale analyses and might shed light on the association between breast cancer and breast density.\n\nPlasma samples from 1329 women in the Swedish KARMA project, without prior history of breast cancer, were profiled with antibody suspension bead array (SBA) assays. Two sample sets comprising 729 and 600 women were screened by two different SBAs targeting a total number of 357 proteins. Protein targets were selected through searching the literature, for either being related to breast cancer or for being linked to the extracellular matrix. Association between proteins and absolute area-based breast density (AD) was assessed by quantile regression, adjusting for age and body mass index (BMI).\n\nPlasma profiling revealed linear association between 20 proteins and AD, concordant in the two sets of samples (p < 0.05). Plasma levels of seven proteins were positively associated and 13 proteins negatively associated with AD. For eleven of these proteins evidence for gene expression in breast tissue existed. Among these, ABCC11, TNFRSF10D, F11R and ERRF were positively associated with AD, and SHC1, CFLAR, ACOX2, ITGB6, RASSF1, FANCD2 and IRX5 were negatively associated with AD.\n\nScreening proteins in plasma indicates associations between breast density and processes of tissue homeostasis, DNA repair, cancer development and/or progression in breast cancer. Further validation and follow-up studies of the shortlisted protein candidates in independent cohorts will be needed to infer their role in breast density and its progression in premenopausal and postmenopausal women.", "doi": "10.1186/s13058-018-0940-z", "pmid": "29444691", "labels": {"Affinity Proteomics Stockholm": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13058-018-0940-z"}, {"db": "pmc", "key": "PMC5813412"}], "notes": [], "created": "2018-10-31T09:21:59.155Z", "modified": "2024-01-16T13:48:46.936Z"}, {"entity": "publication", "iuid": "832d8fd531da49888ca05b6cff3ee534", "links": {"self": {"href": "https://publications.scilifelab.se/publication/832d8fd531da49888ca05b6cff3ee534.json"}, "display": {"href": "https://publications.scilifelab.se/publication/832d8fd531da49888ca05b6cff3ee534"}}, "title": "Determining breast cancer histological grade from RNA-sequencing data.", "authors": [{"family": "Wang", "given": "Mei", "initials": "M"}, {"family": "Klevebring", "given": "Daniel", "initials": "D"}, {"family": "Lindberg", "given": "Johan", "initials": "J"}, {"family": "Czene", "given": "Kamila", "initials": "K"}, {"family": "Gr\u00f6nberg", "given": "Henrik", "initials": "H"}, {"family": "Rantalainen", "given": "Mattias", "initials": "M"}], "type": "journal article", "published": "2016-05-10", "journal": {"volume": "18", "issn": "1465-542X", "issue": "1", "pages": "48", "title": "Breast Cancer Res.", "issn-l": "1465-5411"}, "abstract": "The histologic grade (HG) of breast cancer is an established prognostic factor. The grade is usually reported on a scale ranging from 1 to 3, where grade 3 tumours are the most aggressive. However, grade 2 is associated with an intermediate risk of recurrence, and carries limited information for clinical decision-making. Patients classified as grade 2 are at risk of both under- and over-treatment.\n\nRNA-sequencing analysis was conducted in a cohort of 275 women diagnosed with invasive breast cancer. Multivariate prediction models were developed to classify tumours into high and low transcriptomic grade (TG) based on gene- and isoform-level expression data from RNA-sequencing. HG2 tumours were reclassified according to the prediction model and a recurrence-free survival analysis was performed by the multivariate Cox proportional hazards regression model to assess to what extent the TG model could be used to stratify patients. The prediction model was validated in N=487 breast cancer cases from the The Cancer Genome Atlas (TCGA) data set. Differentially expressed genes and isoforms associated with HGs were analysed using linear models.\n\nThe classification of grade 1 and grade 3 tumours based on RNA-sequencing data achieved high accuracy (area under the receiver operating characteristic curve = 0.97). The association between recurrence-free survival rate and HGs was confirmed in the study population (hazard ratio of grade 3 versus 1 was 2.62 with 95 % confidence interval = 1.04-6.61). The TG model enabled us to reclassify grade 2 tumours as high TG and low TG gene or isoform grade. The risk of recurrence in the high TG group of grade 2 tumours was higher than in low TG group (hazard ratio = 2.43, 95 % confidence interval = 1.13-5.20). We found 8200 genes and 13,809 isoforms that were differentially expressed between HG1 and HG3 breast cancer tumours.\n\nGene- and isoform-level expression data from RNA-sequencing could be utilised to differentiate HG1 and HG3 tumours with high accuracy. We identified a large number of novel genes and isoforms associated with HG. Grade 2 tumours could be reclassified as high and low TG, which has the potential to reduce over- and under-treatment if implemented clinically.", "doi": "10.1186/s13058-016-0710-8", "pmid": "27165105", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13058-016-0710-8"}, {"db": "pmc", "key": "PMC4862203"}], "notes": [], "created": "2017-05-03T13:00:22.821Z", "modified": "2024-01-16T13:48:50.091Z"}, {"entity": "publication", "iuid": "abbffa2b72424f4ea317a691b4554caa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/abbffa2b72424f4ea317a691b4554caa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/abbffa2b72424f4ea317a691b4554caa"}}, "title": "Peroxiredoxin-1 protects estrogen receptor \u03b1 from oxidative stress-induced suppression and is a protein biomarker of favorable prognosis in breast cancer.", "authors": [{"family": "O'Leary", "given": "Patrick C", "initials": "PC"}, {"family": "Terrile", "given": "Marta", "initials": "M"}, {"family": "Bajor", "given": "Malgorzata", "initials": "M"}, {"family": "Gaj", "given": "Pawel", "initials": "P"}, {"family": "Hennessy", "given": "Bryan T", "initials": "BT"}, {"family": "Mills", "given": "Gordon B", "initials": "GB"}, {"family": "Zagozdzon", "given": "Agnieszka", "initials": "A"}, {"family": "O'Connor", "given": "Darran P", "initials": "DP"}, {"family": "Brennan", "given": "Donal J", "initials": "DJ"}, {"family": "Connor", "given": "Kate", "initials": "K"}, {"family": "Li", "given": "Jane", "initials": "J"}, {"family": "Gonzalez-Angulo", "given": "Ana Maria", "initials": "AM"}, {"family": "Sun", "given": "Han-Dong", "initials": "HD"}, {"family": "Pu", "given": "Jian-Xin", "initials": "JX"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Nowis", "given": "Dominika A", "initials": "DA"}, {"family": "Crown", "given": "John P", "initials": "JP"}, {"family": "Zagozdzon", "given": "Radoslaw", "initials": "R"}, {"family": "Gallagher", "given": "William M", "initials": "WM"}], "type": "journal article", "published": "2014-07-10", "journal": {"volume": "16", "issn": "1465-542X", "issue": "4", "pages": "R79", "title": "Breast Cancer Res.", "issn-l": "1465-5411"}, "abstract": "Peroxiredoxin-1 (PRDX1) is a multifunctional protein, acting as a hydrogen peroxide (H2O2) scavenger, molecular chaperone and immune modulator. Although differential PRDX1 expression has been described in many tumors, the potential role of PRDX1 in breast cancer remains highly ambiguous. Using a comprehensive antibody-based proteomics approach, we interrogated PRDX1 protein as a putative biomarker in estrogen receptor (ER)-positive breast cancer.\n\nAn anti-PRDX1 antibody was validated in breast cancer cell lines using immunoblotting, immunohistochemistry and reverse phase protein array (RPPA) technology. PRDX1 protein expression was evaluated in two independent breast cancer cohorts, represented on a screening RPPA (n = 712) and a validation tissue microarray (n = 498). In vitro assays were performed exploring the functional contribution of PRDX1, with oxidative stress conditions mimicked via treatment with H2O2, peroxynitrite, or adenanthin, a PRDX1/2 inhibitor.\n\nIn ER-positive cases, high PRDX1 protein expression is a biomarker of improved prognosis across both cohorts. In the validation cohort, high PRDX1 expression was an independent predictor of improved relapse-free survival (hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.40 to 0.96, P = 0.032), breast cancer-specific survival (HR = 0.44, 95% CI = 0.24 to 0.79, P = 0.006) and overall survival (HR = 0.61, 95% CI = 0.44 to 0.85, P = 0.004). RPPA screening of cancer signaling proteins showed that ER\u03b1 protein was upregulated in PRDX1 high tumors. Exogenous H2O2 treatment decreased ER\u03b1 protein levels in ER-positive cells. PRDX1 knockdown further sensitized cells to H2O2- and peroxynitrite-mediated effects, whilst PRDX1 overexpression protected against this response. Inhibition of PRDX1/2 antioxidant activity with adenanthin dramatically reduced ER\u03b1 levels in breast cancer cells.\n\nPRDX1 is shown to be an independent predictor of improved outcomes in ER-positive breast cancer. Through its antioxidant function, PRDX1 may prevent oxidative stress-mediated ER\u03b1 loss, thereby potentially contributing to maintenance of an ER-positive phenotype in mammary tumors. These results for the first time imply a close connection between biological activity of PRDX1 and regulation of estrogen-mediated signaling in breast cancer.", "doi": "10.1186/bcr3691", "pmid": "25011585", "labels": {"Tissue Profiling": null}, "xrefs": [{"db": "pii", "key": "bcr3691"}, {"db": "pmc", "key": "PMC4226972"}], "notes": [], "created": "2017-05-04T14:56:03.723Z", "modified": "2021-07-08T13:44:33.519Z"}, {"entity": "publication", "iuid": "2554eb3b0bec43aebf752978fa30a3c1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2554eb3b0bec43aebf752978fa30a3c1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2554eb3b0bec43aebf752978fa30a3c1"}}, "title": "Tumor-specific HMG-CoA reductase expression in primary premenopausal breast cancer predicts response to tamoxifen.", "authors": [{"family": "Brennan", "given": "Donal J", "initials": "DJ"}, {"family": "Laursen", "given": "Henriette", "initials": "H"}, {"family": "O'Connor", "given": "Darran P", "initials": "DP"}, {"family": "Borgquist", "given": "Signe", "initials": "S"}, {"family": "Uhlen", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Gallagher", "given": "William M", "initials": "WM"}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F"}, {"family": "Millikan", "given": "Robert C", "initials": "RC"}, {"family": "Ryd\u00e9n", "given": "Lisa", "initials": "L"}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2011-01-31", "journal": {"volume": "13", "issn": "1465-542X", "issue": "1", "pages": "R12", "title": "Breast Cancer Res.", "issn-l": "1465-5411"}, "abstract": "We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined.\n\nHMG-CoAR protein and RNA expression was analyzed in a cell line model of tamoxifen resistance using western blotting and PCR. HMG-CoAR mRNA expression was examined in 155 tamoxifen-treated breast tumors obtained from a previously published gene expression study (Cohort I). HMG-CoAR protein expression was examined in 422 stage II premenopausal breast cancer patients, who had previously participated in a randomized control trial comparing 2 years of tamoxifen with no systemic adjuvant treatment (Cohort II). Kaplan-Meier analysis and Cox proportional hazards modeling were used to estimate the risk of recurrence-free survival (RFS) and the effect of HMG-CoAR expression on tamoxifen response.\n\nHMG-CoAR protein and RNA expression were decreased in tamoxifen-resistant MCF7-LCC9 cells compared with their tamoxifen-sensitive parental cell line. HMG-CoAR mRNA expression was decreased in tumors that recurred following tamoxifen treatment (P < 0.001) and was an independent predictor of RFS in Cohort I (hazard ratio = 0.63, P = 0.009). In Cohort II, adjuvant tamoxifen increased RFS in HMG-CoAR-positive tumors (P = 0.008). Multivariate Cox regression analysis demonstrated that HMG-CoAR was an independent predictor of improved RFS in Cohort II (hazard ratio = 0.67, P = 0.010), and subset analysis revealed that this was maintained in estrogen receptor (ER)-positive patients (hazard ratio = 0.65, P = 0.029). Multivariate interaction analysis demonstrated a difference in tamoxifen efficacy relative to HMG-CoAR expression (P = 0.05). Analysis of tamoxifen response revealed that patients with ER-positive/HMG-CoAR tumors had a significant response to tamoxifen (P = 0.010) as well as patients with ER-positive or HMG-CoAR-positive tumors (P = 0.035). Stratification according to ER and HMG-CoAR status demonstrated that ER-positive/HMG-CoAR-positive tumors had an improved RFS compared with ER-positive/HMG-CoAR-negative tumors in the treatment arm (P = 0.033); this effect was lost in the control arm (P = 0.138), however, suggesting that HMG-CoAR predicts tamoxifen response.\n\nHMG-CoAR expression is a predictor of response to tamoxifen in both ER-positive and ER-negative disease. Premenopausal patients with tumors that express ER or HMG-CoAR respond to adjuvant tamoxifen.", "doi": "10.1186/bcr2820", "pmid": "21281480", "labels": {"Tissue Profiling": null}, "xrefs": [{"db": "pii", "key": "bcr2820"}, {"db": "pmc", "key": "PMC3109580"}], "notes": [], "created": "2017-05-04T14:55:45.527Z", "modified": "2021-07-08T13:44:33.095Z"}], "created": "2017-05-09T09:12:11.625Z", "modified": "2020-11-27T13:14:03.131Z"}