Bjørn Naume

• Ohnstad, Hege Oma; Blix, Egil Støre; Akslen, Lars Andreas; Gilje, Bjørnar; Raj, Sunil Xavier & Skjerven, Helle [Show all 46 contributors for this article] (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.
• Chauhan, Sudhir Kumar; Dunn, Claire; Andresen, Nikolai Kragøe; Røssevold, Andreas Hagen; Skorstad, Gjertrud & Sike, Adam [Show all 11 contributors for this article] (2024). Peripheral immune cells in metastatic breast cancer patients display a systemic immunosuppressed signature consistent with chronic inflammation. NPJ breast cancer. ISSN 2374-4677. 10(1). doi: 10.1038/s41523-024-00638-2.
• Andresen, Nikolai Kragøe; Røssevold, Andreas Hagen; Quaghebeur, Claire; Gilje, Bjørnar; Boge, Beate & Gombos, Andrea [Show all 17 contributors for this article] (2024). Ipilimumab and nivolumab combined with anthracycline-based chemotherapy in metastatic hormone receptor-positive breast cancer: A randomized phase 2b trial. Journal for ImmunoTherapy of Cancer (JITC). 12(1). doi: 10.1136/jitc-2023-007990.
• Morra, Anna; Schreurs, Maartje A. C.; Andrulis, Irene L.; Anton-Culver, Hoda; Augustinsson, Annelie & Beckmann, Matthias W. [Show all 125 contributors for this article] (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), p. 16142–16162. doi: 10.1002/cam4.6272. Full text in Research Archive
• Rugo, Hope S.; Van Poznak, Catherine H.; Neven, Patrick; Danielewicz, Iwona; Lee, Soo Chin & Campone, Mario [Show all 15 contributors for this article] (2023). Radium-223 in women with hormone receptor-positive bone-metastatic breast cancer receiving endocrine therapy: pooled analysis of two international, phase 2, randomized, double-blind, placebo-controlled trials. Breast Cancer Research and Treatment. ISSN 0167-6806. doi: 10.1007/s10549-023-07147-z. Full text in Research Archive
• Levi, Hagai; Carmi, Shai; Rosset, Saharon; Yerushalmi, Rinat; Zick, Aviad & Yablonski-Peretz, Tamar [Show all 155 contributors for this article] (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), p. 1186–1197. doi: 10.1136/jmg-2023-109185. Full text in Research Archive
• Figlioli, Gisella; Billaud, Amandine; Wang, Qin; Bolla, Manjeet K.; Dennis, Joe & Lush, Michael [Show all 96 contributors for this article] (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. Full text in Research Archive
• Figlioli, Gisella; Billaud, Amandine; Ahearn, Thomas U.; Antonenkova, Natalia N.; Becher, Heiko & Beckmann, Matthias W. [Show all 114 contributors for this article] (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), p. 578–587. doi: 10.1038/s41431-022-01257-w. Full text in Research Archive Show summary

  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. [Show all 84 contributors for this article] (2023). The impact of coding germline variants on contralateral breast cancer risk and survival. American Journal of Human Genetics. ISSN 0002-9297. 110(3), p. 475–486. doi: 10.1016/j.ajhg.2023.02.003. Full text in Research Archive
• Mueller, Stefanie H.; Lai, Alvina G.; Valkovskaya, Maria; Michailidou, Kyriaki; Bolla, Manjeet K. & Wang, Qin [Show all 207 contributors for this article] (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. Full text in Research Archive
• Røssevold, Andreas Hagen; Andresen, Nikolai Kragøe; Bjerre, Christina Annette; Gilje, Bjørnar; Jakobsen, Erik Hugger & Raj, Sunil Xavier [Show all 17 contributors for this article] (2022). Atezolizumab plus anthracycline-based chemotherapy in metastatic triple-negative breast cancer: the randomized, double-blind phase 2b ALICE trial. Nature Medicine. ISSN 1078-8956. p. 1–28. doi: 10.1038/s41591-022-02126-1. Full text in Research Archive
• Dixon-Suen, Suzanne C.; Lewis, Sarah; Martin, Richard M.; English, Dallas R.; Boyle, Terry & Giles, Graham G. [Show all 174 contributors for this article] (2022). Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study. British Journal of Sports Medicine. ISSN 0306-3674. 56(20), p. 1157–1170. doi: 10.1136/bjsports-2021-105132. Show summary

  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.

• Staaf, Johan; Häkkinen, Jari; Hegardt, Cecilia; Saal, Lao H.; Kimbung, Siker & Hedenfalk, Ingrid [Show all 25 contributors for this article] (2022). RNA sequencing-based single sample predictors of molecular subtype and risk of recurrence for clinical assessment of early-stage breast cancer. NPJ breast cancer. ISSN 2374-4677. 8:94(1), p. 1–17. doi: 10.1038/s41523-022-00465-3. Full text in Research Archive
• Dorling, Leila; Carvalho, Sara; Allen, Jamie; Parsons, Michael T.; Fortuno, Cristina & Kristensen, Vessela N. [Show all 50 contributors for this article] (2022). Breast cancer risks associated with missense variants in breast cancer susceptibility genes. Genome Medicine. ISSN 1756-994X. 14(1), p. 1–17. doi: 10.1186/s13073-022-01052-8. Full text in Research Archive Show summary

  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

• Bjørklund, Sunniva; Aure, Miriam Ragle; Häkkinen, Jari; Vallon-Christersson, Johan; Kumar, Surendra & Bull Evensen, Katrine [Show all 34 contributors for this article] (2022). Subtype and cell type specific expression of lncRNAs provide insight into breast cancer. Communications Biology. ISSN 2399-3642. 5(1), p. 1–14. doi: 10.1038/s42003-022-03559-7. Full text in Research Archive
• Dennis, Joe; Tyrer, Jonathan P.; Walker, Logan C.; Michailidou, Kyriaki; Dorling, Leila & Kristensen, Vessela N. [Show all 50 contributors for this article] (2022). Rare germline copy number variants (CNVs) and breast cancer risk. Communications Biology. ISSN 2399-3642. 5, p. 1–15. doi: 10.1038/s42003-021-02990-6. Full text in Research Archive Show summary

  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 [Show all 205 contributors for this article] (2022). Common variants in breast cancer risk loci predispose to distinct tumor subtypes. Breast Cancer Research. ISSN 1465-5411. 24(1), p. 1–13. doi: 10.1186/s13058-021-01484-x. Full text in Research Archive
• Nilssen, Yngvar; Brustugun, Odd Terje; Eriksen, Morten Tandberg; Guren, Marianne; Haug, Erik Skaaheim & Naume, Bjørn [Show all 8 contributors for this article] (2022). Compliance with recommended cancer patient pathway timeframes and choice of treatment differed by cancer type and place of residence among cancer patients in Norway in 2015–2016. BMC Cancer. ISSN 1471-2407. 22(220). doi: 10.1186/s12885-022-09306-9. Full text in Research Archive Show summary

  Background Cancer patient pathways (CPPs) were implemented in Norway to reduce unnecessary waiting times, regional variations, and to increase the predictability of cancer care for the patients. This study aimed to determine if 70% of cancer patients started treatment within the recommended time frames, and to identify potential delays. Methods Patients registered with a colorectal, lung, breast, or prostate cancer diagnosis at the Cancer Registry of Norway in 2015–2016 were linked with the Norwegian Patient Registry and Statistics Norway. Adjusting for sociodemographic variables, multivariable quantile (median) regressions were used to examine the association between place of residence and median time to start of examination, treatment decision, and start of treatment. Results The study included 20 668 patients. The proportions of patients who went through the CPP within the recommended time frames were highest among colon (84%) and breast (76%) cancer patients who underwent surgery and lung cancer patients who started systemic anticancer treatment (76%), and lowest for prostate cancer patients who underwent surgery (43%). The time from treatment decision to start of treatment was the main source of delay for all cancers. Travelling outside the resident health trust prolonged waiting time and was associated with a reduced odds of receiving surgery and radiotherapy for lung and rectal cancer patients, respectively. Conclusions Achievement of national recommendations of the CCP times differed by cancer type and treatment. Identified bottlenecks in the pathway should be targeted to decrease waiting times. Further, CPP guidelines should be re-examined to determine their ongoing relevance.

• Park, Hanla A.; Neumeyer, Sonja; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin & Kristensen, Vessela N. [Show all 50 contributors for this article] (2021). Mendelian randomisation study of smoking exposure in relation to breast cancer risk. British Journal of Cancer. ISSN 0007-0920. 125(8), p. 1135–1145. doi: 10.1038/s41416-021-01432-8. Full text in Research Archive
• Johnson, Nichola; Maguire, Sarah; Morra, Anna; Kapoor, Pooja Middha; Tomczyk, Katarzyna & Kristensen, Vessela N. [Show all 50 contributors for this article] (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, p. 842–854. doi: 10.1038/s41416-020-01185-w. Full text in Research Archive
• Rye, Inga Hansine; Huse, Kanutte; Josefsson, Sarah Elisabet; Kildal, Wanja; Danielsen, Håvard Emil Greger & Schlichting, Ellen [Show all 28 contributors for this article] (2021). Breast cancer metastasis: immune profiling of lymph nodes reveals exhaustion of effector T cells and immunosuppression. Molecular Oncology. ISSN 1574-7891. 16(1), p. 88–103. doi: 10.1002/1878-0261.13047. Full text in Research Archive
• Morra, Anna; Escala-Garcia, Maria; Beesley, Jonathan; Keeman, Renske; Canisius, Sander & Ahearn, Thomas U. [Show all 50 contributors for this article] (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), p. 1–18. doi: 10.1186/s13058-021-01450-7. Full text in Research Archive
• Hartkopf, Andreas; Brucker, Sara Y.; Taran, Florin-Andrei; Harbeck, Nadia; Au, Alexandra von & Naume, Bjørn [Show all 37 contributors for this article] (2021). Disseminated tumour cells from the bone marrow of early breast cancer patients: Results from an international pooled analysis. European Journal of Cancer. ISSN 0959-8049. doi: 10.1016/j.ejca.2021.06.028.
• Haugen, Mads Haugland; Lingjærde, Ole Christian; Hedenfalk, Ingrid; Garred, Øystein; Borgen, Elin & Loman, Niklas [Show all 12 contributors for this article] (2021). Protein signature predicts response to neoadjuvant treatment with chemotherapy and bevacizumab in HER2-negative breast cancers. JCO Precision Oncology (JCO PO). 5, p. 286–306. doi: 10.1200/PO.20.00086. Full text in Research Archive
• Park, JooYong; Choi, Ji-Yeob; Choi, Jaesung; Chung, Seokang; Song, Nan & Park, Sue K [Show all 50 contributors for this article] (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), p. 1–21. doi: 10.3390/cancers13102370. Full text in Research Archive
• Nobre, Ana Rita; Risson, Emma; Singh, Deepak K.; Di Martino, Julie S.; Cheung, Julie F. & Wang, Jiapeng [Show all 14 contributors for this article] (2021). Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2. Nature Cancer. doi: 10.1038/s43018-021-00179-8.
• Lien, Tonje Gulbrandsen; Ohnstad, Hege Oma; Lingjærde, Ole Christian; Vallon-Christersson, Johan; Aaserud, Marit & Sveli, My Anh Tu [Show all 12 contributors for this article] (2021). Sample preparation approach influences pam50 risk of recurrence score in early breast cancer. Cancers. ISSN 2072-6694. 13(23). doi: 10.3390/cancers13236118. Full text in Research Archive
• Krüger, Kristi; Silwal-Pandit, Laxmi; Wik, Elisabeth; Straume, Oddbjørn; Stefansson, Ingunn Marie & Borgen, Elin [Show all 10 contributors for this article] (2021). Baseline microvessel density predicts response to neoadjuvant bevacizumab treatment of locally advanced breast cancer. Scientific Reports. ISSN 2045-2322. 11, p. 1–11. doi: 10.1038/s41598-021-81914-0. Full text in Research Archive
• Hugenschmidt, Harald; Labori, Knut Jørgen; Borgen, Elin; Brunborg, Cathrine; Schirmer, Cecilie & Seeberg, Lars Thomas [Show all 8 contributors for this article] (2021). Preoperative CTC-Detection by CellSearch ® Is Associated with Early Distant Metastasis and Impaired Survival in Resected Pancreatic Cancer . Cancers. ISSN 2072-6694. 13(3). doi: 10.3390/cancers13030485. Full text in Research Archive Show summary

  n patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of CTCs-presence on the patterns of recurrence and survival in 98 patients resected for PDAC with 5–10 years of follow-up. Preoperative samples were analysed by the CellSearch® system for EpCAM+/DAPI+/CK+/CD45-CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median disease-free survival (DFS) of 3.3 vs. 9.2 months and a median cancer specific survival (CSS)of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 patients developed distant metastases (DM) and 29 developed isolated local recurrence (ILR) as the first sign of cancer relapse. All patients with CTCs experienced DM. pN-status and histological grade >2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. Preoperative parameters did not affect clinical outcome. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. Preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future

• Liu, Jingjing; van der Smissen, Wendy J. C. Prager; Collee, Margriet J.; Bolla, Manjeet K.; Wang, Qin & Kristensen, Vessela N. [Show all 82 contributors for this article] (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), p. 1–14. doi: 10.1038/s41598-020-65665-y. Full text in Research Archive Show summary

  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.

• Helland, Thomas; Naume, Bjørn; Hustad, Steinar; Bifulco, Ersilia; Kvaløy, Jan Terje & Sætersdal, Anna Barbro [Show all 18 contributors for this article] (2020). Low Z-4OHtam concentrations are associated with adverse clinical outcome among early stage premenopausal breast cancer patients treated with adjuvant tamoxifen. Molecular Oncology. ISSN 1574-7891. doi: 10.1002/1878-0261.12865. Full text in Research Archive Show summary

  Abstract Low steady‐state levels of active tamoxifen metabolites have been associated with inferior treatment outcomes. In this retrospective analysis of 406 estrogen receptor‐positive breast cancer (BC) patients receiving adjuvant tamoxifen as initial treatment, we have associated our previously reported thresholds for the two active metabolites, Z‐endoxifen and Z‐4‐hydroxy‐tamoxifen (Z‐4OHtam), with treatment outcomes in an independent cohort of BC patients. Among all patients, metabolite levels did not affect survival. However, in the premenopausal subgroup receiving tamoxifen alone (n = 191) we confirmed an inferior BC ‐specific survival in patients with the previously described serum concentration threshold of Z‐4OHtam ≤ 3.26 nm (HR = 2.37, 95% CI = 1.02–5.48, P = 0.039). The ‘dose–response’ survival trend in patients categorized to ordinal concentration cut‐points of Z‐4OHtamoxifen (≤ 3.26, 3.27–8.13, > 8.13 nm) was also replicated (P‐trend log‐rank = 0.048). Z‐endoxifen was not associated with outcome. This is the first study to confirm the association between a published active tamoxifen metabolite threshold and BC outcome in an independent patient cohort. Premenopausal patients receiving 5‐year of tamoxifen alone may benefit from therapeutic drug monitoring to ensure tamoxifen effectiveness.

• Kramer, Iris; Hooning, Maartje J.; Mavaddat, Nasim; Hauptmann, Michael; Keeman, Renske & Steyerberg, Ewout W. [Show all 54 contributors for this article] (2020). Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk. American Journal of Human Genetics. ISSN 0002-9297. 107(5), p. 837–848. doi: 10.1016/j.ajhg.2020.09.001. Show summary

  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.

• Kyte, Jon A; Røssevold, Andreas Hagen; Falk, Ragnhild Sørum & Naume, Bjørn (2020). ALICE: A randomized placebo-controlled phase II study evaluating atezolizumab combined with immunogenic chemotherapy in patients with metastatic triple-negative breast cancer. Journal of Translational Medicine. ISSN 1479-5876. 18:252, p. 1–7. doi: 10.1186/s12967-020-02424-7. Full text in Research Archive
• Kyte, Jon A; Andresen, Nikolai Kragøe; Russnes, Hege Elisabeth Giercksky; Fretland, Signe Øien; Falk, Ragnhild Sørum & Lingjærde, Ole Christian [Show all 7 contributors for this article] (2020). ICON: A randomized phase IIb study evaluating immunogenic chemotherapy combined with ipilimumab and nivolumab in patients with metastatic hormone receptor positive breast cancer. Journal of Translational Medicine. ISSN 1479-5876. 18(1). doi: 10.1186/s12967-020-02421-w. Full text in Research Archive
• Hugenschmidt, Harald; Labori, Knut Jørgen; Brunborg, Cathrine; Verbeke, Caroline Sophie; Seeberg, Lars Thomas & Schirmer, Cecilie [Show all 10 contributors for this article] (2020). Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information . BMC Cancer. ISSN 1471-2407. 20:1107, p. 1–13. doi: 10.1186/s12885-020-07510-z. Full text in Research Archive Show summary

  Background: Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC). Methods: Preoperative BM samples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis. Results: Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The proportion of patients with detected CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC). Conclusions: The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed.

• Gythfeldt, Hedda von der Lippe; Lien, Tonje Gulbrandsen; Tekpli, Xavier; Silwal-Pandit, Laxmi; Borgen, Elin & Garred, Øystein [Show all 15 contributors for this article] (2020). Immune phenotype of tumor microenvironment predicts response to bevacizumab in neoadjuvant treatment of ER-positive breast cancer. International Journal of Cancer. ISSN 0020-7136. 147(9), p. 2515–2525. doi: 10.1002/ijc.33108. Full text in Research Archive
• Nilssen, Yngvar; Brustugun, Odd Terje; Eriksen, Morten Tandberg; Haug, Erik Skaaheim; Naume, Bjørn & Møller, Bjørn (2020). Patient and tumour characteristics associated with inclusion in Cancer patient pathways in Norway in 2015-2016. BMC Cancer. ISSN 1471-2407. 20(1), p. 1–11. doi: 10.1186/s12885-020-06979-y. Full text in Research Archive
• Tekpli, Xavier; Lien, Tonje Gulbrandsen; Røssevold, Andreas Hagen; Nebdal, Daniel J.H.; Borgen, Elin & Ohnstad, Hege Oma [Show all 19 contributors for this article] (2019). An independent poor-prognosis subtype of breast cancer defined by a distinct tumor immune microenvironment. Nature Communications. ISSN 2041-1723. 10:5499, p. 1–14. doi: 10.1038/s41467-019-13329-5. Full text in Research Archive
• Hartmann-Johnsen, Olaf Johan; Kåresen, Rolf; Schlichting, Ellen; Naume, Bjørn & Nygård, Jan Franz (2019). Using clinical cancer registry data for estimation of quality indicators: Results from the Norwegian breast cancer registry. International Journal of Medical Informatics. ISSN 1386-5056. 125, p. 102–109. doi: 10.1016/j.ijmedinf.2019.03.004. Full text in Research Archive
• Johansson, Henrik J.; Socciarelli, Fabio; Vacanti, Nathaniel M.; Haugen, Mads Haugland; Zhu, Yafeng & Siavelis, Ioannis [Show all 36 contributors for this article] (2019). Breast cancer quantitative proteome and proteogenomic landscape. Nature Communications. ISSN 2041-1723. 10:1600, p. 1–14. doi: 10.1038/s41467-019-09018-y. Full text in Research Archive
• Nilssen, Yngvar; Brustugun, Odd Terje; Eriksen, Morten Tandberg; Gulbrandsen, Johanne; Haug, Erik Skaaheim & Naume, Bjørn [Show all 7 contributors for this article] (2019). Decreasing waiting time for treatment before and during implementation of cancer patient pathways in Norway. Cancer Epidemiology. ISSN 1877-7821. 61, p. 59–69. doi: 10.1016/j.canep.2019.05.004. Full text in Research Archive
• Møller, Elen Kristine; Nord, Silje; Wedge, David C; Lingjærde, Ole Christian; Silwal-Pandit, Laxmi & Gythfeldt, Hedda [Show all 19 contributors for this article] (2018). Time series analysis of neoadjuvant chemotherapy and bevacizumab-treated breast carcinomas reveals a systemic shift in genomic aberrations. Genome Medicine. ISSN 1756-994X. 10:92. doi: 10.1186/s13073-018-0601-y. Full text in Research Archive
• Di Cosimo, Serena; Campbell, Christine; Azim, Hatem A.; Galli, Giulia; Bregni, Giacomo & Curigliano, Giuseppe [Show all 21 contributors for this article] (2018). The use of breast imaging for predicting response to neoadjuvant lapatinib, trastuzumab and their combination in HER2-positive breast cancer: Results from Neo-ALTTO. European Journal of Cancer. ISSN 0959-8049. 89, p. 42–48. doi: 10.1016/j.ejca.2017.10.036.
• Borgen, Elin; Rypdal, Maria Christine; Sosa, Maria Soledad; Renolen, Anne; Schlichting, Ellen & Lønning, Per Eystein [Show all 9 contributors for this article] (2018). NR2F1 stratifies dormant disseminated tumor cells in breast cancer patients 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis. Breast Cancer Research. ISSN 1465-5411. 20(120), p. 1–13. doi: 10.1186/s13058-018-1049-0. Full text in Research Archive
• Jabeen, Shakila; Espinoza, Jaime; Torland, Lilly Anne; Zucknick, Manuela; Kumar, Surendra & Haakensen, Vilde Drageset [Show all 15 contributors for this article] (2018). Noninvasive profiling of serum cytokines in breast cancer patients and clinicopathological characteristics. Oncoimmunology. ISSN 2162-4011. :e1537691. doi: 10.1080/2162402X.2018.1537691. Full text in Research Archive
• Bidard, François-Clément; Michiels, Stefan; Riethdorf, Sabine; Mueller, Volkmar; Esserman, Laura J. & Lucci, Anthony [Show all 50 contributors for this article] (2018). Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: A Meta-analysis. Journal of the National Cancer Institute. ISSN 0027-8874. 110(6), p. 560–567. doi: 10.1093/jnci/djy018.
• Jabeen, Shakila; Zucknick, Manuela; Nome, Marianne Eikhom; dannenfelser, ruth; Fleischer, Thomas & Kumar, Surendra [Show all 15 contributors for this article] (2018). Serum cytokine levels in breast cancer patients during neoadjuvant treatment with bevacizumab. Oncoimmunology. ISSN 2162-4011. 7(11), p. e1457598-1–e1457598-15. doi: 10.1080/2162402X.2018.1457598.
• Hugenschmidt, Harald; Labori, Knut Jørgen; Brunborg, Cathrine; Verbeke, Caroline Sophie; Seeberg, Lars Thomas & Schirmer, Cecilie [Show all 10 contributors for this article] (2018). Circulating Tumor Cells are an Independent Predictor of Shorter Survival in Patients Undergoing Resection for Pancreatic and Periampullary Adenocarcinoma. Annals of Surgery. ISSN 0003-4932. 271(3), p. 549–558. doi: 10.1097/SLA.0000000000003035.
• Helland, Thomas; Henne, Nina; Bifulco, Ersilia; Naume, Bjørn; Borgen, Elin & Kristensen, Vessela N. [Show all 15 contributors for this article] (2017). Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients. Breast Cancer Research. ISSN 1465-5411. 19(1). doi: 10.1186/s13058-017-0916-4. Full text in Research Archive Show summary

  Background Controversies exist as to whether the genetic polymorphisms of the enzymes responsible for the metabolism of tamoxifen can predict breast cancer outcome in patients using adjuvant tamoxifen. Direct measurement of concentrations of active tamoxifen metabolites in serum may be a more biological plausible and robust approach. We have investigated the association between CYP2D6 genotypes, serum concentrations of active tamoxifen metabolites, and long-term outcome in tamoxifen treated breast cancer patients. Methods From an original observational study comprising 817 breast cancer patients, 99 women with operable breast cancer were retrospectively included in the present study. This cohort of patients were adjuvantly treated with tamoxifen, had provided serum samples suitable for measuring tamoxifen metabolites, and were relapse-free at 3 years after the primary treatment commenced. The median follow-up time from this entry point to breast cancer death was 13.9 years. Patients were CYP2D6 genotyped and grouped into four CYP2D6 phenotype groups (Ultra rapid, extensive, intermediate, and poor metabolizers). Tamoxifen and nine metabolites were quantified in serum (n = 86) and compared with CYP2D6 phenotype groups and outcome. Results Breast cancer patients with low concentrations of Z-4-hydroxy-tamoxifen (Z-4OHtam; ≤ 3.26 nM) had a breast cancer-specific survival (BCSS) of 60% compared to 84% in patients with Z-4OHtam concentrations > 3.26 nM (p = 0.020, log-rank hazard ratio (HR) = 3.56, 95% confidence interval (CI) = 1.14–11.07). For patients with Z-4-hydroxy-N-desmethyl-tamoxifen (Z-endoxifen) levels ≤ 9.00 nM BCSS was 57% compared to 84% for patients with concentrations > 9.00 nM (p = 0.029, HR = 3.73, 95% CI = 1.05–13.22). Low concentrations of Z-4OHtam and Z-endoxifen were associated with poorer survival also after adjusting for clinically relevant variables (HR = 4.27, 95% CI = 1.35–13.58, and HR = 3.70, 95% CI = 1.03–13.25, respectively). Overall survival analysis showed similar survival differences for both active metabolites. The Antiestrogen Activity Score showed comparable effects, but did not improve the prognostic information. Conclusions Patients with Z-4OHtam and Z-endoxifen concentrations lower than 3.26 nM or 9.00 nM, respectively, showed an adverse outcome. Our results suggest that direct measurement of active tamoxifen metabolite concentrations could be of clinical value. Validation in larger study cohorts is warranted.

• Ohnstad, Hege Oma; Borgen, Elin; Falk, Ragnhild Sørum; Lien, Tonje Gulbrandsen; Aaserud, Marit & Sveli, My Anh Tu [Show all 14 contributors for this article] (2017). Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up. Breast Cancer Research. ISSN 1465-5411. 19(120). doi: 10.1186/s13058-017-0911-9. Full text in Research Archive
• Fleischer, Thomas; Tekpli, Xavier; Mathelier, Anthony; Wang, Shixiong; Nebdal, Daniel J.H. & Dhakal, Hari Prasad [Show all 16 contributors for this article] (2017). DNA methylation at enhancers identifies distinct breast cancer lineages. Nature Communications. ISSN 2041-1723. 8(1379). doi: 10.1038/s41467-017-00510-x. Full text in Research Archive
• Gingras, Isabelle; Holmes, Eileen; De Azambuja, Evandro; Nguyen, David H.A.; Izquierdo, Miguel & Zujewski, Jo Anne [Show all 16 contributors for this article] (2017). Regional Nodal Irradiation after Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis from the ALTTO Trial. Journal of the National Cancer Institute. ISSN 0027-8874. 109(8:djw331), p. 1–7. doi: 10.1093/jnci/djw331. Full text in Research Archive
• Nordlund, Marianne Sparby; Westgaard, Arne; Paus, Elisabeth; Øijordsbakken, Miriam; Henanger, Karoline Johansen & Naume, Bjørn [Show all 7 contributors for this article] (2017). Specific antibodies and sensitive immunoassays for the human epidermal growth factor receptors (HER2, HER3, and HER4). Tumour Biology. ISSN 1010-4283. 39(6). doi: 10.1177/1010428317707436. Full text in Research Archive
• Bjørklund, Sunniva Maria Stordal; Panda, Anshuman; Kumar, Surendra; Seiler, Michael; Robinson, Doug & Gheeya, Jinesh [Show all 15 contributors for this article] (2017). Widespread alternative exon usage in clinically distinct subtypes of Invasive Ductal Carcinoma. Scientific Reports. ISSN 2045-2322. 7(1). doi: 10.1038/s41598-017-05537-0. Full text in Research Archive
• dannenfelser, ruth; Nome, Marianne Eikhom; Tahiri, Andliena; Ursini-Siegel, Josie; Vollan, Hans Kristian Moen & Haakensen, Vilde Drageset [Show all 12 contributors for this article] (2017). Data-driven analysis of immune infiltrate in a large cohort of breast cancer and its association with disease progression, ER activity, and genomic complexity. OncoTarget. ISSN 1949-2553. 8(34), p. 57121–57133. doi: 10.18632/oncotarget.19078. Full text in Research Archive Show summary

  The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry. Herein we utilize a machine learning based approach to identify lymphocyte markers with which we can quantify the presence of B cells, cytotoxic T-lymphocytes, T-helper 1, and T-helper 2 cells in any gene expression data set and apply it to studies of breast tissue. By leveraging over 2,100 samples from existing large scale studies, we are able to find an inherent cell heterogeneity in clinically characterized immune infiltrates, a strong link between estrogen receptor activity and infiltration in normal and tumor tissues, changes with genomic complexity, and identify characteristic differences in lymphocyte expression among molecular groupings. With our extendable methodology for capturing cell type specific signal we systematically studied immune infiltration in breast cancer, finding an inverse correlation between beneficial lymphocyte infiltration and estrogen receptor activity in normal breast tissue and reduced infiltration in estrogen receptor negative tumors with high genomic complexity.

• Egeland, Eivind Valen; Pedersen, Kjetil Boye; Park, Daehoon; Synnestvedt, Marit; Sauer, Torill & Naume, Bjørn [Show all 27 contributors for this article] (2017). Prognostic significance of S100A4-expression and subcellular localization in early-stage breast cancer. Breast Cancer Research and Treatment. ISSN 0167-6806. 162(1), p. 127–137. doi: 10.1007/s10549-016-4096-1. Full text in Research Archive
• Silwal-Pandit, Laxmi; Nord, Silje; Gythfeldt, Hedda; Møller, Elen Kristine; Fleischer, Thomas & Rødland, Einar Andreas [Show all 26 contributors for this article] (2017). The longitudinal transcriptional response to neoadjuvant chemotherapy with and without bevacizumab in breast cancer. Clinical Cancer Research. ISSN 1078-0432. 23(16), p. 4662–4670. doi: 10.1158/1078-0432.CCR-17-0160. Full text in Research Archive
• Aure, Miriam Ragle; Vitelli, Valeria; Jernström, Sandra Johanna; Kumar, Surendra; Krohn, Marit & Due, Eldri Undlien [Show all 35 contributors for this article] (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. Full text in Research Archive Show summary

  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.

• Seeberg, Lars Thomas; Brunborg, Cathrine; Waage, Anne; Hugenschmidt, Harald; Renolen, Anne & Stav, Ingunn [Show all 11 contributors for this article] (2017). Survival Impact of Primary Tumor Lymph Node Status and Circulating Tumor Cells in Patients with Colorectal Liver Metastases . Annals of Surgical Oncology. ISSN 1068-9265. 24(8), p. 2113–2121. doi: 10.1245/s10434-017-5818-2.
• Reinertsen, Kristin Valborg; Engebråten, Olav; Loge, Jon Håvard; Småstuen, Milada Cvancarova; Naume, Bjørn & Wist, Erik [Show all 10 contributors for this article] (2017). Fatigue During and After Breast Cancer Therapy—A Prospective Study. Journal of Pain and Symptom Management. ISSN 0885-3924. 53(3), p. 551–560. doi: 10.1016/j.jpainsymman.2016.09.011. Full text in Research Archive
• Jerusalem, Guy; Mariani, Gabriella; Ciruelos, E.M.; Martin, M.; Tjan-Heijnen, V.C.G & Neven, P. [Show all 18 contributors for this article] (2016). Safety of everolimus plus exemestane in patients with hormone-receptor–positive, HER2–negative locally advanced or metastatic breast cancer progressing on prior non-steroidal aromatase inhibitors: primary results of a phase IIIb, open-label, single-arm, expanded-access multicenter trial (BALLET). Annals of Oncology. ISSN 0923-7534. 27(9), p. 1719–1725. doi: 10.1093/annonc/mdw249. Full text in Research Archive
• Demeulemeester, Jonas; Kumar, Parveen; Møller, Elen Kristine; Nord, Silje; Wedge, David C. & Peterson, April [Show all 20 contributors for this article] (2016). Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing. Genome Biology. ISSN 1465-6906. 17(1). doi: 10.1186/s13059-016-1109-7.
• Fleischer, Thomas; Klajic, Jovana; Aure, Miriam Ragle; Louhimo, Riku; Pladsen, Arne Valebjørg & Ottestad, Lars [Show all 18 contributors for this article] (2016). DNA methylation signature (SAM40) identifies subgroups of the Luminal A breast cancer samples with distinct survival. OncoTarget. ISSN 1949-2553. 8(1), p. 1074–1082. doi: 10.18632/oncotarget.13718.
• Sas-Chen, Aldema; Aure, Miriam Ragle; Leibovich, Limor; Carvalho, Silvia; Enuka, Yehoshua & Körner, Cindy [Show all 38 contributors for this article] (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), p. 1052–1064. doi: 10.15252/emmm.201606198. Full text in Research Archive
• Easton, Douglas F; Lesueur, Fabienne; Decker, Brennan; Michailidou, Kyriaki; Li, Jun & Allen, Jamie [Show all 149 contributors for this article] (2016). No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: Implications for gene panel testing. Journal of Medical Genetics. ISSN 0022-2593. 53(5), p. 298–309. doi: 10.1136/jmedgenet-2015-103529.
• Haakensen, Vilde Drageset; Steinfeld, Israel; Saldova, Radka; Shehni, Akram Asadi; Kifer, Ilona & Naume, Bjørn [Show all 9 contributors for this article] (2016). Serum N-glycan analysis in breast cancer patients - Relation to tumour biology and clinical outcome. Molecular Oncology. ISSN 1574-7891. 10(1), p. 59–72. doi: 10.1016/j.molonc.2015.08.002.
• Silwal-Pandit, Laxmi; Russnes, Hege Elisabeth Giercksky; Borgen, Elin; Vang, Veronica Okkenhaug; Vollan, Hans Kristian Moen & Schlichting, Ellen [Show all 11 contributors for this article] (2015). The sub-cellular localization of WRAP53 has prognostic impact in breast cancer. PLOS ONE. ISSN 1932-6203. 10:e0139965(10). doi: 10.1371/journal.pone.0139965. Show summary

  WRAP53 protein controls intracellular trafficking of DNA repair proteins, the telomerase enzyme, and splicing factors. Functional loss of the protein has been linked to carcinogenesis, premature aging and neurodegeneration. The aim of this study was to investigate the prognostic significance of WRAP53 protein expression in breast cancer. A tissue microarray was constructed from primary breast tumors and immunostained by a polyclonal WRAP53 antibody to assess the protein expression pattern. Two different patient cohorts with long term follow-up were studied; a test- and a validation set of 154 and 668 breast tumor samples respectively. Breast cancer patients with tumor cells lacking the expression of WRAP53 in the nucleus had a significantly poorer outcome compared to patients with tumor cells expressing this protein in the nuclei (HR = 1.95, 95%CI = 1.09–3.51, p = 0.025). Nuclear localization of WRAP53 was further shown to be an independent marker of prognosis in multivariate analysis (HR = 2.57, 95%CI = 1.27–5.19, p = 0.008), and also significantly associated with better outcome in patients with TP53 mutation. Here we show that the sub-cellular localization of the WRAP53 protein has a significant impact on breast cancer survival, and thus has a potential as a clinical marker in diagnostics and treatment.

• Brudvik, Kristoffer Watten; Seeberg, Lars Thomas; Hugenschmidt, Harald; Renolen, Anne; Schirmer, Cecilie & Brunborg, Cathrine [Show all 11 contributors for this article] (2015). Detection of Circulating Tumor Cells at Surgery and at Follow-Up Assessment to Predict Survival After Two-Stage Liver Resection of Colorectal Liver Metastases. Annals of Surgical Oncology. ISSN 1068-9265. 22(12), p. 4029–4037. doi: 10.1245/s10434-015-4482-7.
• Bjørklund, Sunniva Maria Stordal; Kristensen, Vessela N.; Seiler, Michael; Kumar, Surendra; Grenaker, Grethe Irene & Ming, Yao [Show all 12 contributors for this article] (2015). Expression of an estrogen-regulated variant transcript of the peroxisomal branched chain fatty acid oxidase ACOX2 in breast carcinomas. BMC Cancer. ISSN 1471-2407. 15(1). doi: 10.1186/s12885-015-1510-8.
• Rye, Inga Hansine; Lundin, Pär; Månér, Susanne; Fjelldal, Renathe; Naume, Bjørn & Wigler, Michael [Show all 10 contributors for this article] (2015). Quantitative multigene FISH on breast carcinomas identifies der(1;16)(q10;p10) as an early event in luminal A tumors. Genes, Chromosomes and Cancer. ISSN 1045-2257. 54(4), p. 235–248. doi: 10.1002/gcc.22237.
• Sahlberg, Kristine Kleivi; Bottai, Giulia; Naume, Bjørn; Burwinkel, Barbara; Calin, George A. & Børresen-Dale, Anne-Lise [Show all 7 contributors for this article] (2015). A Serum MicroRNA Signature Predicts Tumor Relapse and Survival in Triple-Negative Breast Cancer Patients. Clinical Cancer Research. ISSN 1078-0432. 21, p. 1207–1214. doi: 10.1158/1078-0432.CCR-14-2011.
• Seeberg, Lars Thomas; Waage, Anne; Brunborg, Cathrine; Hugenschmidt, Harald; Renolen, Anne & Stav, Ingunn [Show all 11 contributors for this article] (2015). Circulating Tumor Cells in Patients With Colorectal Liver Metastasis Predict Impaired Survival. Annals of Surgery. ISSN 0003-4932. 261(1), p. 164–171. doi: 10.1097/SLA.0000000000000580.
• Reiche, Kristin; Kasack, Katharina; Schreiber, Stephan; Luders, Torben; Due, Eldri Undlien & Naume, Bjørn [Show all 12 contributors for this article] (2014). Long non-coding rnas differentially expressed between normal versus primary breast tumor tissues disclose converse changes to breast cancer-related protein-coding genes. PLOS ONE. ISSN 1932-6203. 9(9). doi: 10.1371/journal.pone.0106076.
• Naume, Bjørn; Synnestvedt, Marit; Falk, Ragnhild Sørum; Wiedswang, Gro; Weyde, Kjetil & Risberg, Terje [Show all 15 contributors for this article] (2014). Clinical Outcome With Correlation to Disseminated Tumor Cell (DTC) Status After DTC-Guided Secondary Adjuvant Treatment With Docetaxel in Early Breast Cancer. Journal of Clinical Oncology. ISSN 0732-183X. 32(34), p. 3848–3857. doi: 10.1200/JCO.2014.56.9327. Show summary

  Purpose: The presence of disseminated tumor cells (DTCs) in bone marrow (BM) predicts survival in early breast cancer. This study explores the use of DTCs for identification of patients insufficiently treated with adjuvant therapy so they can be offered secondary adjuvant treatment and the subsequent surrogate marker potential of DTCs for outcome determination. Patients and Methods: Patients with early breast cancer who had completed six cycles of adjuvant fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapy underwent BM aspiration 2 to 3 months (BM1) and 8 to 9 months (BM2) after FEC. Presence of DTCs in BM was determined by immunocytochemistry using pan-cytokeratin monoclonal antibodies. If one or more DTCs were present at BM2, six cycles of docetaxel (100 mg/m2, once every 3 weeks) were administered, followed by DTC analysis 1 and 13 months after the last docetaxel infusion (after treatment). Cox regression analysis was used to evaluate disease-free interval (DFI). Results: Of 1,066 patients with a DTC result at BM2 and available follow-up information (median follow-up, 71.9 months from the time of BM2), 7.2% were DTC positive. Of 72 docetaxel-treated patients analyzed for DTCs after treatment, 15 (20.8%) had persistent DTCs. Patients with remaining DTCs had markedly reduced DFI (46.7% experienced relapse) compared with patients with no DTCs after treatment (adjusted hazard ratio, 7.58; 95% CI, 2.3 to 24.7). The docetaxel-treated patients with no DTCs after treatment had comparable DFI (8.8% experienced relapse) compared with those with no DTCs both at BM1 and BM2 (12.7% experienced relapse; P = .377, log-rank test). Conclusion: DTC status identifies high-risk patients after FEC chemotherapy, and DTC monitoring status after secondary treatment with docetaxel correlated strongly with survival. This emphasizes the potential for DTC analysis as a surrogate marker for adjuvant treatment effect in breast cancer.

• Ignatiadis, Michail; Riethdorf, Sabine; Bidard, François-Clement; Vaucher, Isabelle; Khazour, Mustapha & Rothé, Françoise [Show all 42 contributors for this article] (2014). International study on inter-reader variability for circulating tumor cells in breast cancer. Breast Cancer Research. ISSN 1465-5411. 16(2). doi: 10.1186/bcr3647.
• Coleman, Robert; Aksnes, Anne-Kirsti; Naume, Bjørn; Garcia, Camilo; Jerusalem, Guy & Piccart, Martine [Show all 9 contributors for this article] (2014). A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease. Breast Cancer Research and Treatment. ISSN 0167-6806. 145(2), p. 411–418. doi: 10.1007/s10549-014-2939-1.
• Fleischer, Thomas; Frigessi, Arnoldo; Johnson, Kevin C.; Edvardsen, Hege; Touleimat, Nizar & Klajic, Jovana [Show all 15 contributors for this article] (2014). Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis. Genome Biology. ISSN 1465-6906. 15. doi: 10.1186/s13059-014-0435-x. Full text in Research Archive Show summary

  Background Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma. DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development. Results We generate genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer, and validate methylation changes between normal and DCIS in an independent dataset of 15 normal and 40 DCIS samples. We also validate a prognostic signature on 583 breast cancer samples from The Cancer Genome Atlas. Our analysis reveals that DNA methylation profiles of DCIS are radically altered compared to normal breast tissue, involving more than 5,000 genes. Changes between DCIS and invasive breast carcinoma involve around 1,000 genes. In tumors, DNA methylation is associated with gene expression of almost 3,000 genes, including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs is associated with survival of breast cancer patients with invasive tumors, as well as with survival of patients with DCIS and mixed lesions of DCIS and invasive breast carcinoma. Conclusions This work demonstrates that changes in the epigenome occur early in the neoplastic progression, provides evidence for the possible utilization of DNA methylation-based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis.

• Gilje, Bjørnar; Nordgård, Oddmund; Tjensvoll, Kjersti; Borgen, Elin; Synnestvedt, Marit & Smaaland, Rune [Show all 7 contributors for this article] (2014). Comparison of molecular and immunocytochemical methods for detection of disseminated tumor cells in bone marrow from early breast cancer patients. BMC Cancer. ISSN 1471-2407. 14(1). doi: 10.1186/1471-2407-14-514.
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  Kreftbehandlingen blir stadig mer kompleks. Flere nye forskningsfunn som gir håp for livsforlengende behandling er nylig blitt lagt fram. På konferansen for American society of clinical oncology (ASCO), den årlige kreftkonferansen i USA, er flere nye behandlingsformer for kreft blitt presentert. Konferansen ble avsluttet tirsdag. - Tradisjonell cellegiftbehandling er kanskje forbi. Immunterapi kommer mot alle kreftformer. Dette er midler som stimulerer kroppens eget immunforsvar, slik at det bedre angriper kreftcellene. Slike medisiner kan brukes mot en rekke kreftformer, som lunge-, nyre- og blærekreft. TKI- hemmere blokkerer mutasjoner som styrer kreftutvikling, og her er det også mange nye behandlingsformer på vei.

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