Jürgen Geisler

• Wang, Feng; Eikeland, Eline; Reidunsdatter, Randi Johansen; Hagen, Lars; Engstrøm, Monica Jernberg & Geisler, Jürgen [Vis alle 10 forfattere av denne artikkelen] (2024). Quantification of multiple steroid hormones in serum and human breast cancer tissue by liquid chromatography-tandem mass spectrometry analysis. Frontiers in Oncology. ISSN 2234-943X. 14. doi: 10.3389/fonc.2024.1383104.
• Ohnstad, Hege Oma; Blix, Egil Støre; Akslen, Lars Andreas; Gilje, Bjørnar; Raj, Sunil Xavier & Skjerven, Helle [Vis alle 46 forfattere av denne artikkelen] (2024). Impact of Prosigna test on adjuvant treatment decision in lymph node-negative early breast cancer—a prospective national multicentre study (EMIT-1). ESMO Open. ISSN 2059-7029. 9(6). doi: 10.1016/j.esmoop.2024.103475.
• Torland, Lilly Anne; Lai, Xiaoran; Kumar, Surendra; Riis, Margit; Geisler, Jürgen & Lüders, Torben [Vis alle 10 forfattere av denne artikkelen] (2024). Benign breast tumors may arise on different immunological backgrounds. Molecular Oncology. ISSN 1574-7891. doi: 10.1002/1878-0261.13655.
• Bertelsen, Bjørn-Erik; Almås, Bjørg; Fjermeros, Kamilla; Viste, kristin; Geisler, Stephanie & Sauer, Torill [Vis alle 8 forfattere av denne artikkelen] (2024). Superior suppression of serum estrogens during neoadjuvant breast cancer treatment with letrozole compared to exemestane. Breast Cancer Research and Treatment. ISSN 0167-6806. doi: 10.1007/s10549-024-07313-x.
• Akman, Tuğba; Arendt, Lisa M.; Geisler, Jürgen; Kristensen, Vessela N.; Frigessi, Arnoldo & Luque, Alvaro Kohn (2024). Modeling of Mouse Experiments Suggests that Optimal Anti-Hormonal Treatment for Breast Cancer is Diet-Dependent. Bulletin of Mathematical Biology. ISSN 0092-8240. 86(4). doi: 10.1007/s11538-023-01253-1.
• Mecinaj, Albulena; Gulati, Geeta; Ree, Anne Hansen; Gravdehaug, Berit; Røsjø, Helge Rørvik & Steine, Kjetil [Vis alle 10 forfattere av denne artikkelen] (2024). Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy–Related Cardiac Dysfunction. JACC: CardioOncology. ISSN 2666-0873. 6(1), s. 83–95. doi: 10.1016/j.jaccao.2023.10.008.
• Tinholt, Mari; Tekpli, Xavier; Torland, Anne Vold; Tahiri, Andliena; Geisler, Jürgen & Kristensen, Vessela [Vis alle 8 forfattere av denne artikkelen] (2024). The breast cancer coagulome in the tumor microenvironment and its role in prognosis and treatment response to chemotherapy. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. doi: 10.1016/j.jtha.2024.01.003.
• Morra, Anna; Schreurs, Maartje A. C.; Andrulis, Irene L.; Anton-Culver, Hoda; Augustinsson, Annelie & Beckmann, Matthias W. [Vis alle 125 forfattere av denne artikkelen] (2023). Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival. Cancer Medicine. ISSN 2045-7634. 12(15), s. 16142–16162. doi: 10.1002/cam4.6272. Fulltekst i vitenarkiv
• Yndestad, Synnøve; Engebrethsen, Christina; Herencia-Ropero, A.; Nikolaienko, Oleksii; Vintermyr, Olav Karsten & Lillestøl, Reidun Kristine [Vis alle 23 forfattere av denne artikkelen] (2023). Homologous Recombination Deficiency Across Subtypes of Primary Breast Cancer. JCO Precision Oncology (JCO PO). 7(7). doi: 10.1200/PO.23.00338. Fulltekst i vitenarkiv
• Nikolaienko, Oleksii; Eikesdal, Hans Petter; Berge, Elisabet Ognedal; Gilje, Bjørnar; Lundgren, Steinar & Blix, Egil Støre [Vis alle 16 forfattere av denne artikkelen] (2023). Prenatal BRCA1 epimutations contribute significantly to triple-negative breast cancer development. Genome Medicine. ISSN 1756-994X. 15(1). doi: 10.1186/s13073-023-01262-8. Fulltekst i vitenarkiv
• Geisler, Jürgen; Karihtala, Peeter; Tuxen, Malgorzata; Valachis, Antonis; Ahlin, Cecilia & Fosskaug, Cathrine Bergquist [Vis alle 28 forfattere av denne artikkelen] (2023). Current treatment landscape of HR+/HER2− advanced breast cancer in the Nordics: a modified Delphi study. Acta Oncologica. ISSN 0284-186X. 62(12), s. 1680–1688. doi: 10.1080/0284186X.2023.2254475. Fulltekst i vitenarkiv
• Levi, Hagai; Carmi, Shai; Rosset, Saharon; Yerushalmi, Rinat; Zick, Aviad & Yablonski-Peretz, Tamar [Vis alle 155 forfattere av denne artikkelen] (2023). Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel. Journal of Medical Genetics. ISSN 0022-2593. 60(12), s. 1186–1197. doi: 10.1136/jmg-2023-109185. Fulltekst i vitenarkiv
• Figlioli, Gisella; Billaud, Amandine; Wang, Qin; Bolla, Manjeet K.; Dennis, Joe & Lush, Michael [Vis alle 96 forfattere av denne artikkelen] (2023). Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases. Cancers. ISSN 2072-6694. 15(13). doi: 10.3390/cancers15133313. Fulltekst i vitenarkiv
• Schandiz, Hossein Khalkhali; Park, Daehoon; Liu, Yan; Lyngra, Marianne; Talleraas, Inger Solvang & Geisler, Jürgen [Vis alle 7 forfattere av denne artikkelen] (2023). Subtypes of high-grade breast ductal carcinoma in situ (DCIS): incidence and potential clinical impact. Breast Cancer Research and Treatment. ISSN 0167-6806. 201(2), s. 329–338. doi: 10.1007/s10549-023-07016-9. Fulltekst i vitenarkiv
• Wang, Feng; Giskeødegård, Guro F.; Skarra, Sissel; Engstrøm, Monica Jernberg; Hagen, Lars & Geisler, Jürgen [Vis alle 11 forfattere av denne artikkelen] (2023). Association of serum cortisol and cortisone levels and risk of recurrence after endocrine treatment in breast cancer. Clinical and Experimental Medicine. ISSN 1591-8890. 23(7), s. 3883–3893. doi: 10.1007/s10238-023-01109-x. Fulltekst i vitenarkiv
• Figlioli, Gisella; Billaud, Amandine; Ahearn, Thomas U.; Antonenkova, Natalia N.; Becher, Heiko & Beckmann, Matthias W. [Vis alle 114 forfattere av denne artikkelen] (2023). FANCM missense variants and breast cancer risk: a case-control association study of 75,156 European women. European Journal of Human Genetics. ISSN 1018-4813. 31(5), s. 578–587. doi: 10.1038/s41431-022-01257-w. Fulltekst i vitenarkiv Vis sammendrag

  Evidence from literature, including the BRIDGES study, indicates that germline protein truncating variants (PTVs) in FANCM confer moderately increased risk of ER-negative and triple-negative breast cancer (TNBC), especially for women with a family history of the disease. Association between FANCM missense variants (MVs) and breast cancer risk has been postulated. In this study, we further used the BRIDGES study to test 689 FANCM MVs for association with breast cancer risk, overall and in ER-negative and TNBC subtypes, in 39,885 cases (7566 selected for family history) and 35,271 controls of European ancestry. Sixteen common MVs were tested individually; the remaining rare 673 MVs were tested by burden analyses considering their position and pathogenicity score. We also conducted a meta-analysis of our results and those from published studies. We did not find evidence for association for any of the 16 variants individually tested. The rare MVs were significantly associated with increased risk of ER-negative breast cancer by burden analysis comparing familial cases to controls (OR = 1.48; 95% CI 1.07–2.04; P = 0.017). Higher ORs were found for the subgroup of MVs located in functional domains or predicted to be pathogenic. The meta-analysis indicated that FANCM MVs overall are associated with breast cancer risk (OR = 1.22; 95% CI 1.08–1.38; P = 0.002). Our results support the definition from previous analyses of FANCM as a moderate-risk breast cancer gene and provide evidence that FANCM MVs could be low/moderate risk factors for ER-negative and TNBC subtypes. Further genetic and functional analyses are necessary to clarify better the increased risks due to FANCM MVs

• Morra, Anna; Mavaddat, Nasim; Muranen, Taru A.; Ahearn, Thomas U.; Allen, Jamie & Andrulis, Irene L. [Vis alle 84 forfattere av denne artikkelen] (2023). The impact of coding germline variants on contralateral breast cancer risk and survival. American Journal of Human Genetics. ISSN 0002-9297. 110(3), s. 475–486. doi: 10.1016/j.ajhg.2023.02.003. Fulltekst i vitenarkiv
• Mueller, Stefanie H.; Lai, Alvina G.; Valkovskaya, Maria; Michailidou, Kyriaki; Bolla, Manjeet K. & Wang, Qin [Vis alle 207 forfattere av denne artikkelen] (2023). Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry. Genome Medicine. ISSN 1756-994X. 15(7). doi: 10.1186/s13073-022-01152-5. Fulltekst i vitenarkiv
• Touma, Joel; Pantalone, Mattia Russel; Rahbar, Afsar; Liu, Yan; Vetvik, Katja K & Sauer, Torill [Vis alle 8 forfattere av denne artikkelen] (2023). Human Cytomegalovirus Protein Expression Is Correlated with Shorter Overall Survival in Breast Cancer Patients: A Cohort Study. Viruses. ISSN 1999-4915. 15(3), s. 1–13. doi: 10.3390/v15030732. Fulltekst i vitenarkiv
• Dixon-Suen, Suzanne C.; Lewis, Sarah; Martin, Richard M.; English, Dallas R.; Boyle, Terry & Giles, Graham G. [Vis alle 174 forfattere av denne artikkelen] (2022). Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study. British Journal of Sports Medicine. ISSN 0306-3674. 56(20), s. 1157–1170. doi: 10.1136/bjsports-2021-105132. Vis sammendrag

  Objectives Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics. Methods We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105–377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity. Results Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger). Conclusion Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.

• Lirussi, Lisa; Ayyildiz, Dilara; Liu, Yan; Montaldo, Nicola Pietro; Carracedo Huroz, Sergio & Aure, Miriam Ragle [Vis alle 16 forfattere av denne artikkelen] (2022). A regulatory network comprising let-7 miRNA and SMUG1 is associated with good prognosis in ER+ breast tumours. Nucleic Acids Research (NAR). ISSN 0305-1048. 50(18), s. 10449–10468. doi: 10.1093/nar/gkac807. Fulltekst i vitenarkiv
• Tahiri, Andliena; Puco, Katarina; Naji, Faris; Kristensen, Vessela N.; Alfsen, G. Cecilie & Farkas, Lorant [Vis alle 10 forfattere av denne artikkelen] (2022). Kinase activity profiling in renal cell carcinoma, benign renal tissue and in response to four different tyrosine kinase inhibitors. OncoTarget. ISSN 1949-2553. 13(1), s. 970–981. doi: 10.18632/oncotarget.28257. Fulltekst i vitenarkiv Vis sammendrag

  Kinase activity is frequently altered in renal cell carcinoma (RCC), and tyrosine kinase inhibitors (TKIs) are part of the standard treatment strategy in patients with metastatic disease. However, there are still no established biomarkers to predict clinical benefits of a specific TKI. Here, we performed protein tyrosine kinase (PTK) profiling using PamChip® technology. The aim of this study was to identify differences in PTK activity between normal and malignant kidney tissue obtained from the same patient, and to investigate the inhibitory effects of TKIs frequently used in the clinics: sunitinib, pazopanib, cabozantinib and tivozanib. Briefly, our results showed that 36 kinase substrates differs (FDR < 0.05) between normal and cancer kidney tissue, where members of the Src family kinases and the phosphoinositide-3-kinase (PI3K) pathway exhibit high activity in renal cancer. Furthermore, ex vivo treatment of clear cell RCC with TKIs revealed that pathways such as Rap1, Ras and PI3K pathways were strongly inhibited, whereas the neurotrophin pathway had increased activity upon TKI addition. In our assay, tivozanib and cabozantinib exhibited greater inhibitory effects on PTK activity compared to sunitinib and pazopanib, implying they might be better suitable as TKIs for selected RCC patients.

• Dorling, Leila; Carvalho, Sara; Allen, Jamie; Parsons, Michael T.; Fortuno, Cristina & Kristensen, Vessela N. [Vis alle 50 forfattere av denne artikkelen] (2022). Breast cancer risks associated with missense variants in breast cancer susceptibility genes. Genome Medicine. ISSN 1756-994X. 14(1), s. 1–17. doi: 10.1186/s13073-022-01052-8. Fulltekst i vitenarkiv Vis sammendrag

  Background: Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. Methods: We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to ana‑ lyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to fve in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. Results: The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47–2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best ftting models were well calibrated in the validation set. Conclusions: These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility

• Venizelos, Andreas; Engebrethsen, Christina; Deng, Wei; Geisler, Jürgen; Geisler, Stephanie & Iversen, Gjertrud Titlestad [Vis alle 18 forfattere av denne artikkelen] (2022). Clonal evolution in primary breast cancers under sequential epirubicin and docetaxel monotherapy. Genome Medicine. ISSN 1756-994X. 14, s. 1–18. doi: 10.1186/s13073-022-01090-2. Fulltekst i vitenarkiv
• Reis, Joana ; Boavida, João; Tran, Hang Thi; Lyngra, Marianne; Reitsma, Laurens Cornelus & Schandiz, Hossein Khalkhali [Vis alle 10 forfattere av denne artikkelen] (2022). Assessment of preoperative axillary nodal disease burden: breast MRI in locally advanced breast cancer before, during and after neoadjuvant endocrine therapy. BMC Cancer. ISSN 1471-2407. 22(1), s. 1–11. doi: 10.1186/s12885-022-09813-9. Fulltekst i vitenarkiv
• Bjørklund, Sunniva; Aure, Miriam Ragle; Häkkinen, Jari; Vallon-Christersson, Johan; Kumar, Surendra & Bull Evensen, Katrine [Vis alle 34 forfattere av denne artikkelen] (2022). Subtype and cell type specific expression of lncRNAs provide insight into breast cancer. Communications Biology. ISSN 2399-3642. 5(1), s. 1–14. doi: 10.1038/s42003-022-03559-7. Fulltekst i vitenarkiv
• Mavaddat, Nasim; Dorling, Leila; Carvalho, Sara; Allen, Jamie; González-Neira, Anna & Keeman, Renske [Vis alle 94 forfattere av denne artikkelen] (2022). Pathology of tumors associated with pathogenic germline variants in 9 breast cancer susceptibility genes. JAMA Oncology. ISSN 2374-2437. 8(3). doi: 10.1001/jamaoncol.2021.6744. Vis sammendrag

  IMPORTANCE Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes are unclear. This information is relevant to guidelines for gene panel testing and risk prediction. OBJECTIVE To characterize tumors associated with BC susceptibility genes in large-scale population- or hospital-based studies. DESIGN, SETTING, AND PARTICIPANTS The multicenter, international case-control analysis of the BRIDGES study included 42 680 patients and 46 387 control participants, comprising women aged 18 to 79 years who were sampled independently of family history from 38 studies. Studies were conducted between 1991 and 2016. Sequencing and analysis took place between 2016 and 2021. EXPOSURES Protein-truncating variants and likely pathogenic missense variants in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53. MAIN OUTCOMES AND MEASURES The intrinsic-like BC subtypes as defined by estrogen receptor, progesterone receptor, and ERBB2 (formerly known as HER2) status, and tumor grade; morphology; size; stage; lymph node involvement; subtype-specific odds ratios (ORs) for carrying protein-truncating variants and pathogenic missense variants in the 9 BC susceptibility genes. RESULTS The mean (SD) ages at interview (control participants) and diagnosis (cases) were 55.1 (11.9) and 55.8 (10.6) years, respectively; all participants were of European or East Asian ethnicity. There was substantial heterogeneity in the distribution of intrinsic subtypes by gene. RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (OR, 6.19 [95% CI, 3.17-12.12]; OR, 6.19 [95% CI, 2.99-12.79]; and OR, 10.05 [95% CI, 5.27-19.19], respectively). CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease. For ATM variants, the association was strongest for the hormone receptor (HR)+ ERBB2− high-grade subtype (OR, 4.99; 95% CI, 3.68-6.76). BRCA1 was associated with increased risk of all subtypes, but the ORs varied widely, being highest for triple-negative disease (OR, 55.32; 95% CI, 40.51-75.55). BRCA2 and PALB2 variants were also associated with triple-negative disease. TP53 variants were most strongly associated with HR+ ERBB2+ and HR– ERBB2+ subtypes. Tumors occurring in pathogenic variant carriers were of higher grade. For most genes and subtypes, a decline in ORs was observed with increasing age. Together, the 9 genes were associated with 27.3% of all triple-negative tumors in women 40 years or younger. CONCLUSIONS AND RELEVANCE The results of this case-control study suggest that variants in the 9 BC risk genes differ substantially in their associated pathology but are generally associated with triple-negative and/or high-grade disease. Knowing the age and tumor subtype distributions associated with individual BC genes can potentially aid guidelines for gene panel testing, risk prediction, and variant classification and guide targeted screening strategies.

• Dennis, Joe; Tyrer, Jonathan P.; Walker, Logan C.; Michailidou, Kyriaki; Dorling, Leila & Kristensen, Vessela N. [Vis alle 50 forfattere av denne artikkelen] (2022). Rare germline copy number variants (CNVs) and breast cancer risk. Communications Biology. ISSN 2399-3642. 5, s. 1–15. doi: 10.1038/s42003-021-02990-6. Fulltekst i vitenarkiv Vis sammendrag

  Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E−18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.

• Ahearn, Thomas U.; Zhang, Haoyu; Michailidou, Kyriaki; Milne, Roger L.; Bolla, Manjeet K. & Dennis, Joe [Vis alle 205 forfattere av denne artikkelen] (2022). Common variants in breast cancer risk loci predispose to distinct tumor subtypes. Breast Cancer Research. ISSN 1465-5411. 24(1), s. 1–13. doi: 10.1186/s13058-021-01484-x. Fulltekst i vitenarkiv
• Park, Hanla A.; Neumeyer, Sonja; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin & Kristensen, Vessela N. [Vis alle 50 forfattere av denne artikkelen] (2021). Mendelian randomisation study of smoking exposure in relation to breast cancer risk. British Journal of Cancer. ISSN 0007-0920. 125(8), s. 1135–1145. doi: 10.1038/s41416-021-01432-8. Fulltekst i vitenarkiv
• Johnson, Nichola; Maguire, Sarah; Morra, Anna; Kapoor, Pooja Middha; Tomczyk, Katarzyna & Kristensen, Vessela N. [Vis alle 50 forfattere av denne artikkelen] (2021). CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers. British Journal of Cancer. ISSN 0007-0920. 124, s. 842–854. doi: 10.1038/s41416-020-01185-w. Fulltekst i vitenarkiv
• Rye, Inga Hansine; Huse, Kanutte; Josefsson, Sarah Elisabet; Kildal, Wanja; Danielsen, Håvard Emil Greger & Schlichting, Ellen [Vis alle 28 forfattere av denne artikkelen] (2021). Breast cancer metastasis: immune profiling of lymph nodes reveals exhaustion of effector T cells and immunosuppression. Molecular Oncology. ISSN 1574-7891. 16(1), s. 88–103. doi: 10.1002/1878-0261.13047. Fulltekst i vitenarkiv
• Morra, Anna; Escala-Garcia, Maria; Beesley, Jonathan; Keeman, Renske; Canisius, Sander & Ahearn, Thomas U. [Vis alle 50 forfattere av denne artikkelen] (2021). Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment. Breast Cancer Research. ISSN 1465-5411. 23:86(1), s. 1–18. doi: 10.1186/s13058-021-01450-7. Fulltekst i vitenarkiv
• Escala-Garcia, Maria; Canisius, Sander; Keeman, Renske; Beesley, Jonathan; Anton-Culver, Hoda & Arndt, Volker [Vis alle 105 forfattere av denne artikkelen] (2021). Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis. Scientific Reports. ISSN 2045-2322. 11:19787, s. 1–11. doi: 10.1038/s41598-021-99409-3. Fulltekst i vitenarkiv Vis sammendrag

  Breast cancer metastasis accounts for most of the deaths from breast cancer. Identifcation of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identifed two germline variants on chromosome 1, rs138569520 and rs146023652, signifcantly associated with breast cancer-specifc survival (P= 3.19 × ­10−8 and 4.42 × ­10−8). In silico analysis suggested a potential regulatory efect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confrm the identifed associations.

• Park, JooYong; Choi, Ji-Yeob; Choi, Jaesung; Chung, Seokang; Song, Nan & Park, Sue K [Vis alle 50 forfattere av denne artikkelen] (2021). Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies? Cancers. ISSN 2072-6694. 13:2370(10), s. 1–21. doi: 10.3390/cancers13102370. Fulltekst i vitenarkiv
• Bertelsen, Bjørn-Erik; Viste, Kristin; Helland, Thomas; Hagland, Magnus; Søiland, Håvard & Geisler, Jürgen [Vis alle 11 forfattere av denne artikkelen] (2021). Simultaneous Quantification of Aromatase Inhibitors and Estrogens in Postmenopausal Breast Cancer Patients. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 107(5), s. 1368–1374. doi: 10.1210/clinem/dgab923. Fulltekst i vitenarkiv
• Mecinaj, Albulena; Gulati, Geeta; Heck, Siri Lagethon; Holte, Espen; Fagerland, Morten Wang & Larsen, Alf Inge [Vis alle 10 forfattere av denne artikkelen] (2021). Rationale and design of the PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA II) trial: a randomized, placebo-controlled, multicenter trial. Cardio-Oncology. ISSN 2057-3804. 7. doi: 10.1186/s40959-021-00115-w. Fulltekst i vitenarkiv Vis sammendrag

  Objective To assess if sacubitril/valsartan given concomitantly with early breast cancer treatment regimens including anthracyclines, with or without trastuzumab, may prevent cardiac dysfunction. Methods PRADA II is a randomized, placebo-controlled, double blind, multi-center, investigator-initiated clinical trial. Breast cancer patients from four university hospitals in Norway, scheduled to receive (neo-)adjuvant chemotherapy with epirubicin independently of additional trastuzumab/pertuzumab treatment, will be randomized 1:1 to sacubitril/valsartan or placebo. The target dose is 97/103 mg b.i.d. The patients will be examined with cardiovascular magnetic resonance (CMR), echocardiography, circulating cardiovascular biomarkers and functional testing at baseline, at end of anthracycline treatment and following 18 months after enrolment. The primary outcome measure of the PRADA II trial is the change in left ventricular ejection fraction (LVEF) by CMR from baseline to 18 months. Secondary outcomes include change in LV function by global longitudinal strain by CMR and echocardiography and change in circulating cardiac troponin concentrations. Results The study is ongoing. Results will be published when the study is completed. Conclusion PRADA II is the first randomized, placebo-controlled study of sacubitril/valsartan in a cardioprotective setting during (neo-)adjuvant breast cancer therapy. It may provide new insight in prevention of cardiotoxicity in patients receiving adjuvant or neo-adjuvant therapy containing anthracyclines. Furthermore, it may enable identification of patients at higher risk of developing cardiotoxicity and identification of those most likely to respond to cardioprotective therapy. Trial registration The trial is registered in the ClinicalTrials.gov registry (identifier NCT03760588). Registered 30 November 2018.

• Bahrami, Nazli; Jabeen, Shakila; Tahiri, Andliena; Sauer, Torill; Ødegård, Hilde Presterud & Geisler, Stephanie Beate [Vis alle 11 forfattere av denne artikkelen] (2021). Lack of cross-resistance between non-steroidal and steroidal aromatase inhibitors in breast cancer patients: the potential role of the adipokine leptin. Breast Cancer Research and Treatment. ISSN 0167-6806. 190, s. 435–449. doi: 10.1007/s10549-021-06399-x. Fulltekst i vitenarkiv
• Reis, Joana; Thomas, Owen; Lahooti, Maryam; Lyngra, Marianne; Schandiz, Hossein Khalkhali & Boavida, João [Vis alle 10 forfattere av denne artikkelen] (2021). Correlation between MRI morphological response patterns and histopathological tumor regression after neoadjuvant endocrine therapy in locally advanced breast cancer: a randomized phase II trial. Breast Cancer Research and Treatment. ISSN 0167-6806. 189, s. 711–723. doi: 10.1007/s10549-021-06343-z. Fulltekst i vitenarkiv
• Heck, Siri Lagethon; Mecinaj, Albulena; Ree, Anne Hansen; Hoffmann, Pavel; Schulz-Menger, Jeanette & Fagerland, Morten [Vis alle 12 forfattere av denne artikkelen] (2021). Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): Extended follow-up of a 2×2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Circulation. ISSN 0009-7322. 143(25), s. 2431–2440. doi: 10.1161/CIRCULATIONAHA.121.054698. Fulltekst i vitenarkiv
• Touma, Joel Joul; Liu, Yan; Rahbar, Afsar; Pantalone, Mattia Russel; Almazan, Nerea Martin & Vetvik, Katja K [Vis alle 9 forfattere av denne artikkelen] (2021). Detection of human cytomegalovirus proteins in paraffin‐embedded breast cancer tissue specimens—a novel, automated immunohistochemical staining protocol. Microorganisms. ISSN 2076-2607. 9(5), s. 1–16. doi: 10.3390/microorganisms9051059. Fulltekst i vitenarkiv
• Liu, Jingjing; van der Smissen, Wendy J. C. Prager; Collee, Margriet J.; Bolla, Manjeet K.; Wang, Qin & Kristensen, Vessela N. [Vis alle 82 forfattere av denne artikkelen] (2020). Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk. Scientific Reports. ISSN 2045-2322. 10:9688(1), s. 1–14. doi: 10.1038/s41598-020-65665-y. Fulltekst i vitenarkiv Vis sammendrag

  In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR=1.035, 95% CI=0.859–1.246, P=0.718 and OR=0.798, 95% CI=0.482–1.322, P=0.381 respectively), nor in specifc high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.

• Kramer, Iris; Hooning, Maartje J.; Mavaddat, Nasim; Hauptmann, Michael; Keeman, Renske & Steyerberg, Ewout W. [Vis alle 54 forfattere av denne artikkelen] (2020). Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. American Journal of Human Genetics. ISSN 0002-9297. 107(5), s. 837–848. doi: 10.1016/j.ajhg.2020.09.001. Vis sammendrag

  Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18–1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02–1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547–0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.

• Broberg, Agneta Månsson; Geisler, Jürgen; Tuohinen, Suvi; Skytta, Tanja; Hrafnkelsdóttir, Þórdís Jóna & Nielsen, Kirsten Melgaard [Vis alle 11 forfattere av denne artikkelen] (2020). Prevention, detection, and management of heart failure in patients treated for breast cancer. Current Heart Failure Reports. ISSN 1546-9530. 17(6), s. 397–408. doi: 10.1007/s11897-020-00486-8. Fulltekst i vitenarkiv
• Eikesdal, Hans Petter; Yndestad, Synnøve; Elzawahry, Asmaa; Llop-Guevara, Alba; Gilje, Bjørnar & Blix, Egil Støre [Vis alle 22 forfattere av denne artikkelen] (2020). Olaparib monotherapy as primary treatment in unselected triple negative breast cancer. Annals of Oncology. ISSN 0923-7534. s. 1–10. doi: 10.1016/j.annonc.2020.11.009. Fulltekst i vitenarkiv
• Reis, Joana ; Lindstrøm, Jonas Christoffer; Boavida, João; Gjesdal, Kjell-Inge; Park, Daehoon & Bahrami, Nazli [Vis alle 11 forfattere av denne artikkelen] (2020). Accuracy of breast MRI in patients receiving neoadjuvant endocrine therapy: comprehensive imaging analysis and correlation with clinical and pathological assessments. Breast Cancer Research and Treatment. ISSN 0167-6806. 184(2), s. 407–420. doi: 10.1007/s10549-020-05852-7. Fulltekst i vitenarkiv
• Bahrami, Nazli; Chang, Gregory; Kanaya, Noriko; Sauer, Torill; Park, Daehoon & Loeng, Marie [Vis alle 9 forfattere av denne artikkelen] (2020). Changes in serum estrogenic activity during neoadjuvant therapy with letrozole and exemestane. Journal of Steroid Biochemistry and Molecular Biology. ISSN 0960-0760. 200, s. 1–8. doi: 10.1016/j.jsbmb.2020.105641. Fulltekst i vitenarkiv
• Tahiri, Andliena; Tekpli, Xavier; Somisetty, Venkata Satheesh; DeWijn, Rik; Luders, Torben & Bukholm, Ida Rashida Khan [Vis alle 9 forfattere av denne artikkelen] (2020). Loss of progesterone receptor is associated with distinct tyrosine kinase profiles in breast cancer. Breast Cancer Research and Treatment. ISSN 0167-6806. 183, s. 585–598. doi: 10.1007/s10549-020-05763-7. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose The aim of this study was to assess protein tyrosine kinase profles in primary breast cancer samples in correlation with the distinct hormone and growth receptor profles ER, PR, and HER2. Experimental design Pamchip® microarrays were used to measure the phosphorylation of 144 tyrosine kinase substrates in 29 ER+breast cancer samples and cell lines MCF7, BT474 and ZR75-1. mRNA expression data from the METABRIC cohort and publicly available PR chip-sequencing data were used for validation purposes, together with RT-PCR. Results In ER+ breast tumors and cell lines, we observed that the loss of PR expression correlated to higher kinase activity in samples and cell lines that were HER2−. A number of kinases, representing mostly proteins within the PI3K/AKT pathway, were identifed as responsible for the diferential phosphorylation between PR− and PR+ in ER+/HER2− tumors. We used the METABRIC cohort to analyze mRNA expression from 977 ER+/HER2− breast cancers. Twenty four kinaseencoding genes were identifed as diferentially expressed between PR+ and PR−, dividing ER+/HER2− samples in two distinct clusters with signifcant diferences in survival (p<0.05). Four kinase genes, LCK, FRK, FGFR4, and MST1R, were identifed as potential direct targets of PR. Conclusions Our results suggest that the PR status has a profound efect on tyrosine kinases, especially for FGFR4 and LCK genes, in ER+/HER2− breast cancer patients. The infuence of these genes on the PI3K/AKT signaling pathway may potentially lead to novel drug targets for ER+/PR− breast cancer patients

• Ny, Lars; Hernberg, Micaela M.; Nyakas, Marta Sølvi; Koivunen, Jussi Pekka; Oddershede, Lars & Yoon, Mie [Vis alle 9 forfattere av denne artikkelen] (2020). BRAF mutational status as a prognostic marker for survival in malignant melanoma: a systematic review and meta-analysis. Acta Oncologica. ISSN 0284-186X. s. 1–13. doi: 10.1080/0284186X.2020.1747636. Fulltekst i vitenarkiv
• Geisler, Jürgen; Touma, Joel; Rahbar, Afsar; Nauclér, Cecilia Söderberg & Vetvik, Katja K (2019). A review of the potential role of human cytomegalovirus (HCMV) infections in breast cancer carcinogenesis and abnormal immunity. Cancers. ISSN 2072-6694. 11:1842(12), s. 1–13. doi: 10.3390/cancers11121842. Fulltekst i vitenarkiv
• Bahrami, Nazli; Sauer, Torill; Engebretsen, Siri Strøm; Aljabri, Mohammad Belal; Bemanian, Vahid & Lindstrøm, Jonas Christoffer [Vis alle 17 forfattere av denne artikkelen] (2019). The NEOLETEXE trial: a neoadjuvant cross-over study exploring the lack of cross resistance between aromatase inhibitors. Future Oncology. ISSN 1479-6694. 15(32), s. 3675–3682. doi: 10.2217/fon-2019-0258. Fulltekst i vitenarkiv
• Langkjer, Sven Tyge; Kenholm, Julia; Jensen, Jeanette Dupont; Wedervang, Kim; Torbøl Brixen, Annette & Grunnet, Mie [Vis alle 16 forfattere av denne artikkelen] (2019). The NAME trial: a direct comparison of classical oral Navelbine versus metronomic Navelbine in metastatic breast cancer. Future Oncology. ISSN 1479-6694. 15(22), s. 2561–2569. doi: 10.2217/fon-2019-0124. Fulltekst i vitenarkiv
• Nauclér, Cecilia Söderberg; Geisler, Jürgen & Vetvik, Katja K (2019). The emerging role of human cytomegalovirus infection in human carcinogenesis: a review of current evidence and potential therapeutic implications. OncoTarget. ISSN 1949-2553. 10(42), s. 4333–4347. doi: 10.18632/oncotarget.27016.
• Costa, Helena; Touma, Joel Joul; Davoudi, Belghis; Benard, Melinda; Sauer, Torill & Geisler, Jürgen [Vis alle 9 forfattere av denne artikkelen] (2019). Human cytomegalovirus infection is correlated with enhanced cyclooxyrgenase-2 and 5-lipoxygenase protein expression in breast cancer. Journal of Cancer Research and Clinical Oncology. ISSN 0171-5216. 145(8), s. 2083–2095. doi: 10.1007/s00432-019-02946-8.
• Bemanian, Vahid; Noone, John Christopher; Sauer, Torill; Touma, Joel Joul; Vetvik, Katja K & Söderberg-Naucler, Cecilia [Vis alle 10 forfattere av denne artikkelen] (2018). Somatic EP300-G211S mutations are associated with overall somatic mutational patterns and breast cancer specific survival in triple-negative breast cancer. Breast Cancer Research and Treatment. ISSN 0167-6806. 2, s. 339–351. doi: 10.1007/s10549-018-4927-3.
• Birkeland, Einar Elvbakken; Zhang, Shan; Poduval, Deepak; Geisler, Jürgen; Nakken, Sigve & Vodak, Daniel [Vis alle 11 forfattere av denne artikkelen] (2018). Patterns of genomic evolution in advanced melanoma. Nature Communications. ISSN 2041-1723. 9:2665, s. 1–12. doi: 10.1038/s41467-018-05063-1. Fulltekst i vitenarkiv
• McNamara, Keely; Guestini, Fouzia; Sauer, Torill; Touma, Joel Joul; Bukholm, Ida Rashida Khan & Lindstrøm, Jonas Christoffer [Vis alle 8 forfattere av denne artikkelen] (2018). In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics. British Journal of Cancer. ISSN 0007-0920. s. 1–9. doi: 10.1038/s41416-018-0034-9. Vis sammendrag

  BACKGROUND: The majority of breast cancer cases are steroid dependent neoplasms, with hormonal manipulation of either CYP19/aromatase or oestrogen receptor alpha axis being the most common therapy. Alternate pathways of steroid actions are documented, but their interconnections and correlations to BC subtypes and clinical outcome could be further explored. METHODS: We evaluated selected steroid receptors (Androgen Receptor, Oestrogen Receptor alpha and Beta, Glucocorticoid Receptor) and oestrogen pathways (steroid sulfatase (STS), 17β-hydroxysteroid dehydrogenase 2 (17βHSD2) and aromatase) in a cohort of 139 BC cases from Norway. Using logistic and cox regression analysis, we examined interactions between these and clinical outcomes such as distant metastasis, local relapse and survival. RESULTS: Our principal finding is an impact of STS expression on the risk for distant metastasis (p<0.001) and local relapses (p <0.001), HER2 subtype (p<0.015), and survival (p<0.001). The suggestion of a beneficial effect of alternative oestrogen synthesis pathways was strengthened by inverted, but non-significant findings for 17βHSD2. CONCLUSIONS: Increased intratumoural metabolism of oestrogens through STS is associated with significantly lower incidence of relapse and/or distant metastasis and correspondingly improved prognosis. The enrichment of STS in the HER2 overexpressing subtype is intriguing, especially given the possible role of HER-2 over-expression in endocrine resistance.

• Heck, Siri Lagethon; Gulati, Geeta; HOFFMANN, PAVEL; von Knobelsdorff-Brenkenhoff, Florian; Storås, Tryggve & Ree, Anne Hansen [Vis alle 12 forfattere av denne artikkelen] (2018). Effect of candesartan and metoprolol on myocardial tissue composition during anthracycline treatment: The PRADA trial. European Heart Journal-Cardiovascular Imaging. ISSN 2047-2404. 19(5), s. 544–552. doi: 10.1093/ehjci/jex159. Fulltekst i vitenarkiv Vis sammendrag

  Aims: Anthracycline treatment may cause myocyte loss and expansion of the myocardial extracellular volume (ECV) fraction by oedema and fibrosis. We tested the hypotheses that adjuvant treatment for early breast cancer with the anthracycline epirubicin is dose dependently associated with increased ECV fraction and total ECV, as well as reduced total myocardial cellular volume, and that these changes could be prevented by concomitant angiotensin or beta-adrenergic blockade. Methods and results: PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) was a 2 × 2 factorial, placebo-controlled, double-blinded trial of candesartan and metoprolol. Sixty-nine women had valid ECV measurements. ECV fraction, total ECV, and total cellular volume were measured by cardiovascular magnetic resonance before and at the completion of anthracycline therapy. ECV fraction increased from 27.5 ± 2.7% to 28.6 ± 2.9% (P = 0.002). A cumulative doxorubicin equivalent dose of 268 mg/m2 was associated with greater increase in ECV fraction than doses <268 mg/m2 (mean change 3.4% [95% confidence interval (CI) 1.2, 5.5] vs. 0.7% [95% CI 0.0, 1.5], P = 0.006), as well as greater increase in total ECV (1.9 mL [95% CI 0.4, 3.5] vs. 0.1 mL [95% CI -0.6, 0.8], P = 0.04). In patients receiving candesartan, total cellular volume decreased (-3.5 mL [95% CI - 4.7, -2.2], P < 0.001) while in patients not receiving candesartan, it remained unchanged (P = 0.45; between group difference P = 0.003). Conclusions: Anthracycline therapy is associated with dose-dependent increase in ECV fraction and total ECV. Concomitant treatment with candesartan reduces left ventricular total cellular volume.

• Gulati, Geeta; Heck, Siri Lagethon; Røsjø, Helge; Ree, Anne Hansen; HOFFMANN, PAVEL & Hagve, Tor-Arne [Vis alle 11 forfattere av denne artikkelen] (2017). Neurohormonal blockade and circulating cardiovascular biomarkers during anthracycline therapy in breast cancer patients: Results from the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) study. Journal of the American Heart Association (JAHA). ISSN 2047-9980. 6(11). doi: 10.1161/JAHA.117.006513. Fulltekst i vitenarkiv
• Rahbar, Afsar; Touma, Joel; Costa, Helena; Davoudi, Belghis; Bukholm, Ida Rashida Khan & Sauer, Torill [Vis alle 9 forfattere av denne artikkelen] (2017). Low Expression of Estrogen Receptor-α and Progesterone Receptor in Human Breast Cancer Tissues Is Associated With High-Grade Human Cytomegalovirus Protein Expression. Clinical Breast Cancer. ISSN 1526-8209. 17(7), s. 526–535.e1. doi: 10.1016/j.clbc.2017.04.013. Fulltekst i vitenarkiv
• Aure, Miriam Ragle; Vitelli, Valeria; Jernström, Sandra Johanna; Kumar, Surendra; Krohn, Marit & Due, Eldri Undlien [Vis alle 35 forfattere av denne artikkelen] (2017). Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome. Breast Cancer Research. ISSN 1465-5411. 19. doi: 10.1186/s13058-017-0812-y. Fulltekst i vitenarkiv Vis sammendrag

  Background Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a “cluster-of-clusters” approach with consensus clustering. Results Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. Conclusions The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.

• Daldorff, Stine; Ruud, Randi Margit; Yri, Olav Erich; Ødegård, Hilde Presterud & Geisler, Jürgen (2017). Cotargeting of CYP-19 (aromatase) and emerging, pivotal signaling pathways in metastatic breast cancer. British Journal of Cancer. ISSN 0007-0920. 116(1), s. 10–20. doi: 10.1038/bjc.2016.405.
• Sas-Chen, Aldema; Aure, Miriam Ragle; Leibovich, Limor; Carvalho, Silvia; Enuka, Yehoshua & Körner, Cindy [Vis alle 38 forfattere av denne artikkelen] (2016). LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated in aggressive breast cancer. EMBO Molecular Medicine. ISSN 1757-4676. 8(9), s. 1052–1064. doi: 10.15252/emmm.201606198. Fulltekst i vitenarkiv
• Gulati, Geeta; Heck, Siri Lagethon; Ree, Anne Hansen; HOFFMANN, PAVEL; Schulz-Menger, Jeanette & Fagerland, Morten [Vis alle 15 forfattere av denne artikkelen] (2016). Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. European Heart Journal. ISSN 0195-668X. 37(21), s. 1671–1680. doi: 10.1093/eurheartj/ehw022.
• Flågeng, Marianne Hauglid; Larionov, Alexey; Geisler, Jürgen; Knappskog, Stian; Prestvik, Wenche S & Bjørkøy, Geir [Vis alle 11 forfattere av denne artikkelen] (2016). Treatment with aromatase inhibitors stimulates the expression of epidermal growth factor receptor-1 and neuregulin 1 in ER positive/HER-2/neu non-amplified primary breast cancers. Journal of Steroid Biochemistry and Molecular Biology. ISSN 0960-0760. 165, s. 228–235. doi: 10.1016/j.jsbmb.2016.06.011.

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• Straume, Oddbjørn; Geisler, Jürgen; Gullestad, Hans Petter; Nyakas, Marta Sølvi; Jacobsen, Kari Dolven & Aamdal, Steinar (2016). MEDIKAMENTELL KREFTBEHANDLING - Cytostatikaboken 8. utgave, Kapittel 34 - Malignt melanom. Universitetet i Oslo. ISBN 978-82-992331-4-9. 661 s.
• Mellgren, Gunnar; Angelsen, Anders; Eikesdal, Hans Petter & Geisler, Jürgen (2016). MEDIKAMENTELL KREFTBEHANDLING - CYTOSTATIKABOKEN Kapittel 19 - Hormoner og antihormoner . Universitetet i Oslo. ISBN 978-82-992331-4-9. 661 s.

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• Giskeødegård, Guro F.; Wang, Feng; Sauer, Torill; Selsås, Knut; Geisler, Jürgen & Bathen, Tone Frost (2023). Changes in serum metabolic profiles during breast cancer treatment with aromatase inhibitors.
• Giskeødegård, Guro F.; Wang, Feng; Sauer, Torill; Selsås, Knut; Geisler, Jürgen & Bathen, Tone Frost (2023). Changes in serum metabolic profiles during breast cancer treatment with aromatase inhibitors.
• Schandiz, Hossein; Park, Daehoon; Kaiser, Yan Liu; Lyngra, Marianne; Solvang Talleraas, Ingrid & Geisler, Jürgen [Vis alle 7 forfattere av denne artikkelen] (2022). A novel diagnostics approach to Ductal Carcinoma In Situ (DCIS) with potential impact on the therapeutic algorithms. Cancer Prevention Research. ISSN 1940-6207. 15(12 Supplement 1; abstract A015).
• Eikeland, Eline; Giskeødegård, Guro F.; Reidunsdatter, Randi Johansen; Engstrøm, Monica Jernberg; Hagen, Lars & Geisler, Jürgen [Vis alle 10 forfattere av denne artikkelen] (2022). Liquid Chromatography-Tandem Mass Spectrometry Analysis of Steroid Hormones in Serum and Breast Cancer Tissue.
• Wang, Feng; Giskeødegård, Guro F.; Skarra, Sissel; Engstrøm, Monica Jernberg; Hagen, Lars & Geisler, Jürgen [Vis alle 10 forfattere av denne artikkelen] (2022). Association of serum steroid hormone concentrations with endocrine treatment resistance in patients with breast cancer.
• Reis, Joana ; Lindstrøm, Jonas; Boavida, João; Gjesdal, Kjell-Inge; Sauer, Torill & Geisler, Jürgen [Vis alle 7 forfattere av denne artikkelen] (2021). Accuracy of breast MRI in patients receiving neoadjuvant endocrine therapy: Comprehensive imaging analysis and correlation with clinical and pathological assessments.
• Broberg, Agneta Månsson; Tuohinen, Suvi; Skytta, Tanja; Geisler, Jürgen; Hrafnkelsdóttir, þórdís Jóna & Smáradóttir, Agnes [Vis alle 10 forfattere av denne artikkelen] (2020). The Establishment of the Nordic Cardio-Oncology Society. JACC: CardioOncology. ISSN 2666-0873. 2(2), s. 333–335. doi: 10.1016/j.jaccao.2020.04.004.
• Reis, Joana ; Kristiansen, Cathrine Helgestad; Boavida, João; Lindstrøm, Jonas Christoffer; Sauer, Torill & Geisler, Jürgen [Vis alle 7 forfattere av denne artikkelen] (2020). Dual-layer spectral detector CT: Clinical performance in patients with locally advanced breast cancer treated neoadjuvant with aromatase inhibitors. Annals of Oncology. ISSN 0923-7534.
• Vaske, Charlie; Parulkar, R.; Bahrami, Nazli; Sauer, Torill; Lüders, Torben & Lorentzen, Annika [Vis alle 9 forfattere av denne artikkelen] (2019). Time-course DNA and RNA profiling reveals down-regulation of all members of the sulfotransferase 1A subfamily during neoadjuvant therapy with aromatase inhibitors.
• Eikesdal, Hans Petter; Clausen, Christina; Blix, Egil Støre; Lundgren, Steinar; Vagstad, Geirfinn & Espelid, Helge [Vis alle 13 forfattere av denne artikkelen] (2019). Neoadjuvant endocrine therapy with palbociclib in patients with high-risk breast cancer.
• Eikesdal, Hans Petter; Yndestad, Synnøve; Blix, Egil Støre; Lundgren, Steinar; Vagstad, Geirfinn & Espelid, Helge [Vis alle 13 forfattere av denne artikkelen] (2019). Neoadjuvant olaparib monotherapy in primary triple negative breast cancer.
• Bahrami, Nazli; Jabeen, Shakila; Sauer, Torill; Kristensen, Vessela N.; Gundersen, Joanna M. & Geisler, Jürgen (2019). The aromatase inactivator exemestane suppresses serum leptin levels significantly in vivo - in contrast to the aromatase inhibitor letrozole.
• Langkjer, Sven Tyge; Kenholm, Julia; Jensen, Jeanette Dupont; Wedervang, Kim; Brixen, Annette Torbøl & Grunnet, Mie [Vis alle 15 forfattere av denne artikkelen] (2018). The NAME trial: A direct comparison of oral navelbine given either classic or metronomic in metastatic HER2 neg breast cancer. Annals of Oncology. ISSN 0923-7534. 29, s. viii120–viii120. doi: 10.1093/annonc/mdy272.354.
• Vaske, Charlie; Bahrami, Nazli; Parulkar, R.; Newton, Y.; Sauer, Torill & Loeng, Marie [Vis alle 11 forfattere av denne artikkelen] (2018). Time-course DNA and RNA profiling of tumors from intra-patient cross-over trial of sequential use of aromatase inhibitors.
• Bahrami, Nazli; Chang, G.; Kanaya, N.; Sauer, Torill; Loeng, Marie & Gravdehaug, Berit [Vis alle 8 forfattere av denne artikkelen] (2018). Total estrogenic activity during neoadjuvant therapy with letrozole and exemestane: An intra-patient cross-over comparison using the AroEr tri-screen.
• Bahrami, Nazli; Sauer, Torill; Loeng, Marie; Gravdehaug, Berit; Engebretsen, Siri & Aljabri, Belal [Vis alle 11 forfattere av denne artikkelen] (2018). The NEO-LET-EXE trial: an intra-patient cross-over study to explore the lack of cross-resistance between steroidal and nonsteroidal aromatase inhibitors .
• Langkjer, Sven Tyge; Kenholm, J; Jensen, J.D.; Wedervang, K.; Brixen, A.T. & Grunnet, M. [Vis alle 15 forfattere av denne artikkelen] (2018). The NAME trial: A direct comparison of oral Navelbine given either classic or metronomic in metastatic, HER-2 negative breast cancer .
• Vetvik, Katja K; Touma, Joel Joul; Söderberg-Naucler, Cecilia; Sauer, Torill; Rahbar, Afsar & Geisler, Jürgen (2018). Lavt hormonreseptoruttrykk (ØR/PGR) er koblet til høygradig cytomegalovirusinfeksjon hos pasienter med brystkreft. Best Practice Onkologi/Hematologi. s. 1–11.
• Ny, Lars; Nyakas, Marta Sølvi; Hernberg, Micaela; Koivunen, Jussi; Oddershede, Lars & Yoon, Mie Ran [Vis alle 9 forfattere av denne artikkelen] (2018). BRAF Mutational Status as a Prognostic Marker for Survival in Malignant Melanoma: A Systematic Review and Meta-Analysis. Abstract number for publication: e21566.
• Touma, Joel Joul; Rahbar, Afsar; Davoudi, B; Lindstrøm, Jonas Christoffer; Sauer, Torill & Bukholm, Ida Rashida Khan [Vis alle 9 forfattere av denne artikkelen] (2018). The prognostic impact of Human Cytomegalivirus (HCMV) infection in breast cancer - evaluation of recurrence and survival.
• Bemanian, Vahid; Sauer, Torill; Touma, Joel Joul; Vetvik, Katja K; Noone, John Christopher & Kristensen, Vessela N. [Vis alle 8 forfattere av denne artikkelen] (2017). The EP300.G211S mutation is highly associated with low overall mutational burden in triple-negative breast cancer patients.
• Rahbar, Afsar; Touma, Joel; Costa, Helena; Davoudi, B; Vetvik, Katja K & Geisler, Jürgen [Vis alle 7 forfattere av denne artikkelen] (2016). Low expression levels of hormone receptors (ER-alpha and PGR) in human breast cancer samples is significantly associated with high-grade human cytomegalovirus-IEA.
• Costa, Helena; Touma, Joel; Davoudi, B; Geisler, Jürgen; Vetvik, Katja K & Söderberg Naucler, Cecilia [Vis alle 7 forfattere av denne artikkelen] (2016). High-grade human cytomegalovirus IEA is associated with expression of COX-2 and 5-LO in human breast cancer samples.
• McNamara, Keely; Guestini, F; Sauer, Torill; Lindstrøm, Jonas Christoffer; Sasano, Hironobu & Geisler, Jürgen (2016). Steroid receptors and steroidogenic enzymes in human breast cancer: Associations with breast cancer subtypes and clinical outcome.
• Bemanian, Vahid; Sauer, Torill; Touma, Joel; Vetvik, Katja K; Kristensen, Vessela N. & Bukholm, Ida Rashida Khan [Vis alle 7 forfattere av denne artikkelen] (2016). Next generation sequencing (NGS) reveals high mutation rates in all established breast cancer subtypes with type-specific patterns.
• Heck, Siri Lagethon; Gulati, Geeta; HOFFMANN, PAVEL; von Knobelsdorff-Brenkenhoff, Florian; Storås, Tryggve & Ree, Anne Hansen [Vis alle 11 forfattere av denne artikkelen] (2016). Effects of Candesartan and Metoprolol on Myocardial Mass, Edema, and Fibrosis During Anthracycline Treatment in Early Breast Cancer: APRADA-CMR substudy.
• Gulati, Geeta; Heck, Siri Lagethon; Geisler, Jürgen; Gravdehaug, Berit; Ree, Anne Hansen & HOFFMANN, PAVEL [Vis alle 9 forfattere av denne artikkelen] (2016). Atrio-ventricular plane excursion is impaired after ten weeks of anthracycline treatment in breast cancer patients; Data from the PRADA-study.
• Gulati, Geeta; Heck, Siri Lagethon; Geisler, Jürgen; Gravdehaug, Berit; HOFFMANN, PAVEL & Steine, Kjetil [Vis alle 9 forfattere av denne artikkelen] (2016). Troponin I and Cardiac Function During Breast Cancer Therapy in Human Epidermal Growth Factor Receptor 2 Positive and Negative Patients: Results from the PRADA Study.
• Bemanian, Vahid; Sauer, Torill; Touma, Joel; Vetvik, Katja K; Chen, Ying & Kristensen, Vessela N. [Vis alle 8 forfattere av denne artikkelen] (2016). Next generation sequencing (NGS) reveals high mutation rates in established and potentially novel cancer genes in triple-negative breast cancer. Cancer Research. ISSN 0008-5472. 76. doi: 10.1158/1538-7445.AM2016-LB-246.
• Gulati, Geeta; Heck, Siri Lagethon; Geisler, Jürgen; Fagerland, Morten; HOFFMANN, PAVEL & Gravdehaug, Berit [Vis alle 10 forfattere av denne artikkelen] (2016). Effect of candesartan and metoprolol on subclinical myocardial injury during anthracycline therapy: data from the prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA) study.
• Gulati, Geeta; Heck, Siri Lagethon; HOFFMANN, PAVEL; Ree, Anne Hansen; Schulz-Menger, Jeanette & von Knobelsdorff-Brenkenhoff, Florian [Vis alle 12 forfattere av denne artikkelen] (2016). Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): Primary Results of a Randomized, 2 x 2 Factorial, Placebo-Controlled, Double-Blind Clinical Trial. Circulation. ISSN 0009-7322.
• Tahiri, Andliena; De Wijn, Rik; Venkata, Satheesh; Luders, Torben; Aure, Miriam Ragle & Quigley, David [Vis alle 9 forfattere av denne artikkelen] (2015). Protein Tyrosine Kinase Activity and miRNA Expression Profiling Reveals Differences According to Progesterone-Receptor-Status in HER2 Negative Breast Cancer .
• Bemanian, Vahid; Sauer, Torill; Touma, Joel; Lindstedt, Bjørn-Arne; Chen, Ying & Ødegård, Hilde Presterud [Vis alle 8 forfattere av denne artikkelen] (2015). The EGFR gatekeeper mutation T790M is present in selected patients with early breast cancer. Proceedings of the American Association of Cancer Research. ISSN 0197-016X. 56(1), s. 28–29.

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