Helle Kristine Skjerven

• Boniface, Jana de; Meretoja, Tuomo; Rydén, Lisa; Sund, Malin; Karlsson, Per & Huang, Chiun Sheng [Show all 30 contributors for this article] (2026). Omission of axillary lymph node dissection in ultrasound-detectable axillary metastases in primary breast cancer treated by upfront surgery: prospective randomized SENOMAC-ULTRA non-inferiority trial. BJS Open. 10(4). doi: 10.1093/bjsopen/zrag083.
• Dalen, Christin E. Bang; Simtniece, Zane; Maierhofer, Ursa; Skjerven, Helle Kristine; Linos, Konstantinos & Papathomas, Thomas (2026). Unraveling an Under-Recognized Entity Involving the Nipple Areolar Complex: Challenge. American journal of dermatopathology. ISSN 0193-1091. 48(8), p. e65–e66. doi: 10.1097/DAD.0000000000003313. Full text in Research Archive
• Dalen, Christin E. Bang; Simtniece, Zane; Maierhofer, Urša; Skjerven, Helle Kristine; Linos, Konstantinos & Papathomas, Thomas (2026). Unraveling an Under-Recognized Entity Involving the Nipple Areolar Complex: Answer. American journal of dermatopathology. ISSN 0193-1091. 48(8), p. 650–652. doi: 10.1097/DAD.0000000000003314. Full text in Research Archive
• Spillum, Maren-Kathrine Guriby; Sahlberg, Guro Kristine Kleivi; Skjerven, Helle Kristine & Mjøsund, Nina Helen (2026). Nurses' and Physicians' Experiences With Digital Remote Patient Monitoring—Transforming the Boundaries of Breast Cancer Care. Journal of Clinical Nursing (JCN). ISSN 0962-1067. doi: 10.1111/jocn.70394. Full text in Research Archive
• Fjørtoft, Marit Otterlei; Garred, Øystein; Lingjærde, Ole Christian; Johannesen, Karin Teien; Ottestad, Lars & Bergheim, Inger Riise [Show all 29 contributors for this article] (2025). Single-cell analysis reveals tumour size as a key driver of immune cell profile alterations in primary breast tumours and corresponding lymph nodes. BJC Reports. 3(1). doi: 10.1038/s44276-025-00152-3. Full text in Research Archive Show summary

  At diagnosis, 30–40% of women with breast cancer have metastases in sentinel (SN) or axillary lymph nodes (ALN). Nodal status is a strong prognostic factor and guides treatment decisions. Immune checkpoint inhibition has shown some efficacy, which can increase in the neoadjuvant setting. A better understanding of how tumour cells in primary tumours and metastatic lymph nodes shape the local immune microenvironment may provide clues for more individualized therapeutic interventions. Methods We conducted deep immunophenotypic analysis of 29 primary breast tumours and 36 lymph nodes from 38 patients with primary operable breast cancer. Results The immune profile of the primary tumour was not predictive of the lymph node immune profile or metastatic status. Primary tumours showed prominent CD8 T cell exhaustion and activated regulatory T cells, and the frequencies of these subsets were associated with tumour size. The immune cell profile in lymph nodes were different from the profile in primary tumours, except for the ALN+ nodes, which displayed a T-cell profile more similar to primary tumours. The frequencies of the T cell subsets in lymph nodeswere associated with metastatic size. Tumour cells from smaller metastases exhibited a distinct phenotype compared to those from larger tumour deposits, and the size of the tumour cell deposit impacted the local immune cell composition. Conclusion The tumour size of primary tumours and metastatic size in lymph nodes are the main drivers of changes in immune cell composition

• Asphaug, Lars; Akslen, Lars Andreas; Blix, Egil Støre; Boge, Beate; Borgen, Elin Faye & Brekke, Marianne B. [Show all 28 contributors for this article] (2025). Cost-Effectiveness of Prosigna for Adjuvant Treatment Decisions in Early Breast Cancer: Healthcare Sector and Societal Perspectives. Clinical Breast Cancer. ISSN 1526-8209. 25(6), p. e721–e730. doi: 10.1016/j.clbc.2025.04.011. Full text in Research Archive Show summary

  Background Gene expression profiling tests such as the Prosigna-assay are used to aid adjuvant treatment decisions in hormone receptor positive (HR+) HER2 negative (HER2-) early breast cancer (EBC). In this economic evaluation, the cost-effectiveness of Prosigna against immunohistochemical (IHC) markers including Ki-67, was evaluated from the Norwegian healthcare- and societal perspective. Materials and methods The impact of Prosigna on the treatment decision was assessed in the prospective, observational EMIT-1 trial. Using individual data collected during the first 12 months post-surgery, a decision model was built to project the economic consequences of using the Prosigna compared to IHC-markers for adjuvant treatment decisions. A bottom-up costing analysis assessed the two strategies' material- and labour costs. Health benefits were measured by cost per quality-adjusted life-years (QALYs) using the EQ-5D-5L questionnaire and data on income and welfare benefits was obtained from Statistics Norway. Results Of 2,178 HR+/HER2- pN0 EBC patients in the EMIT-1 trial, 1,985 had available health economic data and 1,850 had complete income and welfare benefit records. Including all pN0 patients in the Prosigna-test strategy, the test was above the cost-effective threshold (€26,000; incremental cost-per QALY gained (ICER) €255,622) in a healthcare sector perspective. Applying a societal perspective incorporating productivity costs, Prosigna was cost saving (ICER €-435,677). Restricting Prosigna-testing to patients assessed as chemotherapy candidates/uncertain chemotherapy candidates, the strategy was cost-effective from both the healthcare and societal perspective (ICER €8,884 and €-620,170, respectively). For other subgroups (pT>1cm, ≤/>50 years), cost-effectiveness was only achievable from a societal perspective (ICER €-574,911, €-602,955 and €-336,832, respectively). Conclusions Using the Prosigna-assay for all HR+/HER2- pN0 EBC patients was not cost-effective from a healthcare perspective, but from the societal perspective it was cost-saving compared to the IHC-classification. Selecting patients who are clear/uncertain candidates for chemotherapy based on IHC-classification, Prosigna is cost-effective from both perspectives. Micro-abstract This economic evaluation assessed the cost-effectiveness of the Prosigna gene expression profiling test versus immunohistochemical (IHC) markers for adjuvant treatment decisions in hormone receptor positive (HR+) HER2 negative (HER2-) early breast cancer (EBC) from Norwegian healthcare and societal perspectives. The Prosigna test was not cost-effective from a healthcare perspective but was cost-saving from a societal perspective. When use was restricted to patients who were clear chemotherapy candidates or uncertain candidates, Prosigna was cost-effective from both perspectives.

• Sharma, Abhibhav; Debik, Julia; Naume, Bjørn; Ohnstad, Hege Oma; Sahlberg, Guro Kristine Kleivi & Borgen, Elin [Show all 25 contributors for this article] (2024). Comprehensive multi-omics analysis of breast cancer reveals distinct long-term prognostic subtypes. Oncogenesis. 13(1), p. 1–13. doi: 10.1038/s41389-024-00521-6. Full text in Research Archive Show summary

  Breast cancer (BC) is a leading cause of cancer-related death worldwide. The diverse nature and heterogeneous biology of BC pose challenges for survival prediction, as patients with similar diagnoses often respond differently to treatment. Clinically relevant BC intrinsic subtypes have been established through gene expression profiling and are implemented in the clinic. While these intrinsic subtypes show a significant association with clinical outcomes, their long-term survival prediction beyond 5 years often deviates from expected clinical outcomes. This study aimed to identify naturally occurring long-term prognostic subgroups of BC based on an integrated multi-omics analysis. This study incorporates a clinical cohort of 335 untreated BC patients from the Oslo2 study with long-term follow-up (>12 years). Multi-Omics Factor Analysis (MOFA+) was employed to integrate transcriptomic, proteomic, and metabolomic data obtained from the tumor tissues. Our analysis revealed three prominent multi-omics clusters of BC patients with significantly different long-term prognoses (p = 0.005). The multi-omics clusters were validated in two independent large cohorts, METABRIC and TCGA. Importantly, a lack of prognostic association to long-term follow-up above 12 years in the previously established intrinsic subtypes was shown for these cohorts. Through a systems-biology approach, we identified varying enrichment levels of cell-cycle and immune-related pathways among the prognostic clusters. Integrated multi-omics analysis of BC revealed three distinct clusters with unique clinical and biological characteristics. Notably, these multi-omics clusters displayed robust associations with long-term survival, outperforming the established intrinsic subtypes.

• Kildal, Wanja; Cyll, Karolina Urszula; Kalsnes, Joakim; Islam, Rakibul; Julbø, Frida Marie Ihle & Pradhan, Manohar [Show all 35 contributors for this article] (2024). Deep learning for automated scoring of immunohistochemically stained tumour tissue sections – Validation across tumour types based on patient outcomes. Heliyon. 10(13), p. 1–19. doi: 10.1016/j.heliyon.2024.e32529. Full text in Research Archive Show summary

  We aimed to develop deep learning (DL) models to detect protein expression in immunohistochemically (IHC) stained tissue-sections, and to compare their accuracy and performance with manually scored clinically relevant proteins in common cancer types. Five cancer patient cohorts (colon, two prostate, breast, and endometrial) were included. We developed separate DL models for scoring IHC-stained tissue-sections with nuclear, cytoplasmic, and membranous staining patterns. For training, we used images with annotations of cells with positive and negative staining from the colon cohort stained for Ki-67 and PMS2 (nuclear model), the prostate cohort 1 stained for PTEN (cytoplasmic model) and β-catenin (membranous model). The nuclear DL model was validated for MSH6 in the colon, MSH6 and PMS2 in the endometrium, Ki-67 and CyclinB1 in prostate, and oestrogen and progesterone receptors in the breast cancer cohorts. The cytoplasmic DL model was validated for PTEN and Mapre2, and the membranous DL model for CD44 and Flotillin1, all in prostate cohorts. When comparing the results of manual and DL scores in the validation sets, using manual scores as the ground truth, we observed an average correct classification rate of 91.5 % (76.9–98.5 %) for the nuclear model, 85.6 % (73.3–96.6 %) for the cytoplasmic model, and 78.4 % (75.5–84.3 %) for the membranous model. In survival analyses, manual and DL scores showed similar prognostic impact, with similar hazard ratios and p-values for all DL models. Our findings demonstrate that DL models offer a promising alternative to manual IHC scoring, providing efficiency and reproducibility across various data sources and markers.

• Ohnstad, Hege Oma; Blix, Egil Støre; Akslen, Lars Andreas; Gilje, Bjørnar; Raj, Sunil Xavier & Skjerven, Helle [Show all 45 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. 9(6), p. 1–12. doi: 10.1016/j.esmoop.2024.103475. Full text in Research Archive Show summary

  Background EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. Patients and methods Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians’ treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed. Results Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). Conclusion The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.

• 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

• Skjerven, Helle; Myklebust, Even Moa; Korvald, Christian; Stubberud, Kjetil; Hovda, Tone & Porojnicu, Alina Carmen [Show all 10 contributors for this article] (2023). Long-term follow-up of complex oncoplastic breast-conserving surgery, standard breast conservation and skin-sparing mastectomy in DCIS - a register-based study. European Journal of Surgical Oncology. ISSN 0748-7983. 50(2). doi: 10.1016/j.ejso.2023.107938. Full text in Research Archive
• Hamersma, Dave T.; Schreuder, Kay; Geleijnse, Gijs; Heeg, Erik; Cellamare, Matteo & Lobbes, Marc B. I. [Show all 12 contributors for this article] (2023). Comparing quality of breast cancer care in the Netherlands and Norway by federated propensity score analytics. Breast Cancer Research and Treatment. ISSN 0167-6806. 201(2), p. 247–256. doi: 10.1007/s10549-023-06986-0. Full text in Research Archive Show summary

  Purpose - The aim of the study was to benchmark and compare breast cancer care quality indicators (QIs) between Norway and the Netherlands using federated analytics preventing transfer of patient-level data.<p> <p>Methods - Breast cancer patients (2017–2018) were retrieved from the Netherlands Cancer Registry and the Cancer Registry of Norway. Five European Society of Breast Cancer Specialists (EUSOMA) QIs were assessed: two on magnetic resonance imaging (MRI), two on surgical approaches, and one on postoperative radiotherapy. The QI outcomes were calculated using ‘Vantage 6’ federated Propensity Score Stratification (PSS). Likelihood of receiving a treatment was expressed in odds ratios (OR).<p> <p>Results - In total, 39,163 patients were included (32,786 from the Netherlands and 6377 from Norway). PSS scores were comparable to the crude outcomes of the QIs. The Netherlands scored higher on the QI ‘proportions of patients preoperatively examined with breast MRI’ [37% vs.17.5%; OR 2.8 (95% CI 2.7–2.9)], the ‘proportions of patients receiving primary systemic therapy examined with breast MRI’ [83.3% vs. 70.8%; OR 2.3 (95% CI 1.3–3.3)], and ‘proportion of patients receiving a single breast operation’ [95.2% vs. 91.5%; OR 1.8 (95% CI 1.4–2.2)]. Country scores for ‘immediate breast reconstruction’ and ‘postoperative radiotherapy after breast-conserving surgery’ were comparable. The EUSOMA standard was achieved in both countries for 4/5 indicators.<p> <p>Conclusion - Both countries achieved high scores on the QIs. Differences were observed in the use of MRI and proportion of patients receiving single surgery. The federated approach supports future possibilities on benchmark QIs without transfer of privacy-sensitive data.

• Skjerven, Helle; Myklebust, Even Moa; Korvald, Christian; Porojnicu, Alina Carmen; Kåresen, Rolf & Hofvind, Solveig Sand-Hanssen [Show all 8 contributors for this article] (2022). Oncological outcomes after simple and skin-sparing mastectomy of ductal carcinoma in situ: A register-based cohort study of 576 Norwegian women. European Journal of Surgical Oncology. ISSN 0748-7983. doi: 10.1016/j.ejso.2022.11.594. Full text in Research Archive
• Brunvoll, Sonja Hjellegjerde; Flote, Vidar Gordon; Halset, Eline Holli; Bertheussen, Gro Falkener; Skjerven, Helle & Lømo, Jon [Show all 8 contributors for this article] (2022). Normal and unusual days for dietary intake during the 12 months after a breast cancer diagnosis in women. European Journal of Nutrition. ISSN 1436-6207. 61, p. 3873–3885. doi: 10.1007/s00394-022-02925-9. Full text in Research Archive Show summary

  Purpose There are several reasons to report days as being unusual with regard to dietary intake, including special occasions and celebrations. For breast cancer patients during the 12 month post-surgery period, unusual days may also include days that are affected by being a cancer patient. The aim of this study was to study dietary intake on “normal” and “unusual” days, and to study what is reported in “free text fields” of a food diary. Methods Women (n = 456), mean age 55.5 years newly diagnosed with invasive breast cancer (stage I/II) were included in this clinical study. “Normal” and “unusual” days in general, over time and during the week and weekends were studied using repeated administration of a 7-day pre-coded food diary. Results The breast cancer patients reported 26% of all days as unusual. The intake of energy, most nutrients, especially alcohol and sugar, red and processed meat, and sweets, cakes, and snacks was 5–126% higher, whereas intake of fiber, fruit and berries, vegetables, and dairy products was 7–17% lower on unusual than on normal days (P < 0.001). The same pattern was seen for normal/unusual days during the weekdays, weekends and over time. Finally, 99% of the breast cancer patients used the free text fields to report additional intake with a mean energy of 1.1 MJ/day. Conclusion For breast cancer patients during the 12-month post-surgery period, unusual days are important drivers of total intake, especially for alcohol. The free text fields in the pre-coded food diary contributed substantially to the total intake.

• Bjørklund, Sunniva; Aure, Miriam Ragle; Häkkinen, Jari; Vallon-Christersson, Johan; Kumar, Surendra & Evensen, Katrine Bull [Show all 34 contributors for this article] (2022). Subtype and cell type specific expression of lncRNAs provide insight into breast cancer. Communications Biology. 5(1), p. 1–14. doi: 10.1038/s42003-022-03559-7. Full text in Research Archive Show summary

  Abstract Long non-coding RNAs (lncRNAs) are involved in breast cancer pathogenesis through chromatin remodeling, transcriptional and post-transcriptional gene regulation. We report robust associations between lncRNA expression and breast cancer clinicopathological features in two population-based cohorts: SCAN-B and TCGA. Using co-expression analysis of lncRNAs with protein coding genes, we discovered three distinct clusters of lncRNAs. In silico cell type deconvolution coupled with single-cell RNA-seq analyses revealed that these three clusters were driven by cell type specific expression of lncRNAs. In one cluster lncRNAs were expressed by cancer cells and were mostly associated with the estrogen signaling pathways. In the two other clusters, lncRNAs were expressed either by immune cells or fibroblasts of the tumor microenvironment. To further investigate the cis-regulatory regions driving lncRNA expression in breast cancer, we identified subtype-specific transcription factor (TF) occupancy at lncRNA promoters. We also integrated lncRNA expression with DNA methylation data to identify long-range regulatory regions for lncRNA which were validated using ChiA-Pet-Pol2 loops. lncRNAs play an important role in shaping the gene regulatory landscape in breast cancer. We provide a detailed subtype and cell type-specific expression of lncRNA, which improves the understanding of underlying transcriptional regulation in breast cancer.

• Skjerven, Helle; Danielsen, Anders Skyrud; Schlichting, Ellen; Sahlberg, Kristine Kleivi & Hofvind, Solveig Sand-Hanssen (2022). Treatment of Ductal Carcinoma in situ: A Register-Based Study of Norwegian Women Diagnosed between 1995 and 2018. Breast Care. ISSN 1661-3791. 17(5), p. 486–494. doi: 10.1159/000524564. Full text in Research Archive Show summary

  The incidence of ductal carcinoma in situ (DCIS) has increased after implementation of mammographic screening. The lesion represents management challenges due to its undetermined growth pattern. We aimed to explore treatment of women aged 48–71 years diagnosed with DCIS between 1995 and 2018, by detection mode and histopathological characteristics. Material and Methods: Data on surgical treatment and radiation therapy (RT) of 4,995 women diagnosed with DCIS were retrieved from the Cancer Registry of Norway. We described the percentage and frequency of breast-conserving treatment (BCT) for participants in BreastScreen Norway (screen-detected) and nonparticipants. We estimated the relative risk (RR) of BCT, using log-binomial regression models. Results: Use of BCT increased from about 40% in 1995 to 85% in 2018. Use of BCT was more common among older than younger women and more commonly used for screen-detected versus tumors detected outside the screening program. Nine out of ten women with tumors ≤10 mm were treated with BCT and two out of ten with tumors >50 mm. RT was given to 89.3% of the women with tumors ≤10 mm, 34.1% of those with tumors classified as van Nuys’ grade 1 and <10 mm and 96.0% of the tumors >50 mm. Use of BCT was less common for tumors >50 mm compared to <10 mm (RR adjusted for age, detection mode, van Nuys’ grade, and localization: 0.26, 95% CI: 0.19–0.36). Conclusion: BCT was increasingly used among women diagnosed with DCIS in Norway during the period from 1995 to 2018, particularly for screen-detected, small lesions with low van Nuys’ grade.

• Skjerven, Helle; Trewin, Cassia Bree & Østby, Kjersti (2022). The Norwegian Breast Cancer Registry (NBCR): A clinical register that monitors surgical care with the intention to increase the quality of treatment given to breast cancer patients in Norway. Norsk Epidemiologi. ISSN 0803-2491. 30(1-2), p. 41–46. doi: 10.5324/nje.v30i1-2.4976. 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 Show summary

  Sentinel lymph nodes are the first nodes draining the lymph from a breast and could reveal early changes in the host immune system upon dissemination of breast cancer cells. To investigate this, we performed single-cell immune profiling of lymph nodes with and without metastatic cells. Whereas no significant changes were observed for B-cell and natural killer (NK)-cell subsets, metastatic lymph nodes had a significantly increased frequency of CD8 T cells and a skewing toward an effector/memory phenotype of CD4 and CD8 T cells, suggesting an ongoing immune response. Additionally, metastatic lymph nodes had an increased frequency of TIGIT (T-cell immunoreceptor with Ig and ITIM domains)-positive T cells with suppressed TCR signaling compared with non-metastatic nodes, indicating exhaustion of effector T cells, and an increased frequency of regulatory T cells (Tregs) with an activated phenotype. T-cell alterations correlated with the percentage of metastatic tumor cells, reflecting the presence of metastatic tumor cells driving T effector cells toward exhaustion and promoting immunosuppression by recruitment or increased differentiation toward Tregs. These results show that immune suppression occurs already in early stages of tumor progression.

• Liu, Jingjing; Smissen, Wendy J. C. Prager van der; 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. 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.

• Brunvoll, Sonja Hjellegjerde; Thune, Inger; Bertheussen, Gro Falkener; Fjeldheim, Frøydis Nyborg; Flote, Vidar Gordon & Frydenberg, Hanne [Show all 13 contributors for this article] (2020). Dietary changes in early-stage breast cancer patients from pre-surgery and over the 12 months post-surgery. British Journal of Nutrition. ISSN 0007-1145. 125(2), p. 172–182. doi: 10.1017/S0007114520002627. Full text in Research Archive Show summary

  The time after a breast cancer diagnosis is a potential period for making positive dietary changes, but previous results are conflicting. The main aim of the present study was to study breast cancer patients’ dietary changes during the 12 months post-surgery and from 12 months pre-surgery to 12 months post-surgery with repeated administration of a 7-d pre-coded food diary and an FFQ, respectively. Women (n 506), mean age 55·3 years diagnosed with invasive breast cancer (stages I and II), were included. The dietary intake was quite stable over time, but the intake was lower for energy (0·3 and 0·4 MJ/d), alcohol (1·9 and 1·5 g/d) and vegetables (17 and 22 g/d) at 6 months than 3 weeks post-surgery (food diary) and at 12 months post-surgery than pre-surgery (FFQ), respectively. Furthermore, energy percentage (E%) from carbohydrates increased between 0·8 and 1·2 E% and E% from fat decreased between 0·6 and 0·8 E% over time, measured by both dietary assessment methods. We observed a higher intake of dairy products (11 g/d) at 6 months post-surgery (food diary), and a lower intake of dairy products (34 g/d) and red and processed meat (7·2 g/d) at 12 months post-surgery (FFQ). Moreover, 24 % of the patients claimed they made dietary changes, but mostly they did not change their diet differently compared with those patients who claimed no changes. In conclusion, breast cancer patients reported only minor dietary changes from 12 months pre-surgery and during the 12 months post-surgery.

• Skjerven, Helle; Danielsen, Anders Skyrud; Schlichting, Ellen; Sahlberg, Kristine Kleivi & Hofvind, Solveig (2020). Kirurgisk behandling av brystkreft i Norge 2003–18. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.20.0090. Full text in Research Archive Show summary

  BAKGRUNN Brystbevarende kirurgi er anbefalt i Norge og internasjonalt ved brystkreft påvist i et tidlig stadium. Vi har analysert operasjonsmetode for brystkreftpasienter etter behandlende sykehus, alder ved diagnose, deteksjonsmetode og svulstenes histopatologiske karakteristikk for perioden fra 2003 til 2018. MATERIALE OG METODE Informasjon om kvinner i alle aldre diagnostisert med infiltrerende brystkreft (n = 47 004) ble hentet fra Kreftregisterets databaser. Vi ekskluderte kvinner med fjernmetastaser ved diagnose (n = 1 773) og de uten registrert operasjonsmetode (n = 2 638). Deteksjonsmetode ble definert som screeningoppdaget brystkreft, intervallkreft eller brystkreft påvist utenfor Mammografiprogrammet. Valg av operasjonsmetode ble sammenlignet ved deskriptive analyser. RESULTATER Noe over halvparten (23 661 av 42 593, dvs. 55,6 %) av kvinnene som fikk påvist brystkreft i studieperioden, ble operert med brystbevarende kirurgi. Andelen økte fra 1 189/2 423 (49,1 %) i 2003 til 2 070/2 958 (70,0 %) i 2018. Det var store forskjeller mellom sykehusene. I perioden 2015–18 fant vi den høyeste andelen brystbevarende kirurgi, 175/187 (93,6 %), ved screeningoppdaget brystkreft operert på Ålesund sjukehus, mens vi fant den laveste andelen, 121/351 (34,5 %), blant kvinner med brystkreft påvist utenfor Mammografiprogrammet, operert på Radiumhospitalet. Brystbevarende kirurgi ble oftest benyttet hos kvinner med små svulster uten spredning til lymfeknuter i armhulen. FORTOLKNING Vi fant betydelige forskjeller i operasjonsmetode for brystkreft mellom sykehusene og mellom ulike deteksjonsmetodene.

• 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 Show summary

  Antiangiogenic drugs are potentially a useful supplement to neoadjuvant chemotherapy for a subgroup of patients with human epidermal growth factor receptor 2 (HER2) negative breast cancer, but reliable biomarkers for improved response are lacking. Here, we report on a randomized phase II clinical trial to study the added effect of bevacizumab in neoadjuvant chemotherapy with FEC100 (5‐fluorouracil, epirubicin and cyclophosphamide) and taxanes (n = 132 patients). Gene expression from the tumors was obtained before neoadjuvant treatment, and treatment response was evaluated by residual cancer burden (RCB) at time of surgery. Bevacizumab increased the proportion of complete responders (RCB class 0) from 5% to 20% among patients with estrogen receptor (ER) positive tumors (P = .02). Treatment with bevacizumab was associated with improved 8‐year disease‐free survival (P = .03) among the good responders (RCB class 0 or I). Patients treated with paclitaxel (n = 45) responded better than those treated with docetaxel (n = 21; P = .03). Improved treatment response was associated with higher proliferation rate and an immune phenotype characterized by high presence of classically activated M1 macrophages, activated NK cells and memory activated CD4 T cells. Treatment with bevacizumab increased the number of adverse events, including hemorrhage, hypertension, infection and febrile neutropenia, but despite this, the ECOG status was not affected.

• 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 Show summary

  Purpose: Chemotherapy-induced alterations to gene expression are due to transcriptional reprogramming of tumor cells or subclonal adaptations to treatment. The effect on whole-transcriptome mRNA expression was investigated in a randomized phase II clinical trial to assess the effect of neoadjuvant chemotherapy with the addition of bevacizumab. Experimental Design: Tumor biopsies and whole-transcriptome mRNA profiles were obtained at three fixed time points with 66 patients in each arm. Altogether, 358 specimens from 132 patients were available, representing the transcriptional state before treatment start, at 12 weeks and after treatment (25 weeks). Pathologic complete response (pCR) in breast and axillary nodes was the primary endpoint. Results: pCR was observed in 15 patients (23%) receiving bevacizumab and chemotherapy and 8 patients (12%) receiving only chemotherapy. In the estrogen receptor–positive patients, 11 of 54 (20%) treated with bevacizumab and chemotherapy achieved pCR, while only 3 of 57 (5%) treated with chemotherapy reached pCR. In patients with estrogen receptor–positive tumors treated with combination therapy, an elevated immune activity was associated with good response. Proliferation was reduced after treatment in both treatment arms and most pronounced in the combination therapy arm, where the reduction in proliferation accelerated during treatment. Transcriptional alterations during therapy were subtype specific, and the effect of adding bevacizumab was most evident for luminal-B tumors. Conclusions: Clinical response and gene expression response differed between patients receiving combination therapy and chemotherapy alone. The results may guide identification of patients likely to benefit from antiangiogenic therapy.

• Tangerud, Åse; Potapenko, Ivan Olegovich; Skjerven, Helle & Stensrud, Mats Julius (2016). Radiologic evaluation of lumps in the male breast. Acta Radiologica. ISSN 0284-1851. 57(7), p. 809–814. doi: 10.1177/0284185115609802. Full text in Research Archive
• 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 Show summary

  Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basal‐like subtype associates with increased EGFR signaling, while another, the HER2‐enriched subtype, engages a kin of EGFR. Based on the premise that EGFR‐regulated lncRNAs might control the aggressiveness of basal‐like tumors, we identified multiple EGFR‐inducible lncRNAs in basal‐like normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal‐like and in HER2‐positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo. In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers.

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• Østby, Kjersti & Skjerven, Helle Kristine (2026). Årsrapport 2025 med resultater og forbedringstiltak fra Nasjonalt kvalitetsregister for brystkreft. Full text in Research Archive
• Fjermeros, Kamilla; Ghannoum, Salim; Geisler, Stephanie; Bhargava, Sameer; Tahiri, Andliena & Klajic, Jovana [Show all 32 contributors for this article] (2024). The NEOLETRIB trial: neoadjuvant treatment with Letrozole and Ribociclib in ER-positive, HER2-negative breast cancer. Future Oncology. ISSN 1479-6694. 20(32), p. 2457–2466. doi: 10.1080/14796694.2024.2377531. Full text in Research Archive Show summary

  Chemotherapy is used as neoadjuvant therapy for all subgroups of breast cancer, including ER-positive, and HER2-negative cases. However, studies have suggested that using aromatase inhibitors combined with CDK4/6-inhibitors might be an appropriate alternative in selected patients. Thus, the NEOLETRIB trial evaluates the response of ER-positive, HER2-negative luminal A/B breast cancer to the combination of letrozole and ribociclib in the neoadjuvant setting. Comprehensive molecular biology procedures, including sequential single-cell RNA-sequencing of tumor biopsies, are performed during 6 months of treatment with extensive biobanking of blood samples, tumor biopsies and gut microbiome specimens. Our findings will hopefully contribute to an improved selection of patients who may benefit from this drug combination and give new insights into the intra-tumoral changes during this treatment.

• Svendsen, Karianne; Nes, Lise Solberg; Meland, Anders; Larsson, Ine Marie; Gjelsvik, Ylva M. & Børøsund, Elin [Show all 17 contributors for this article] (2023). Coping After Breast Cancer: Protocol for a Randomized Controlled Trial of Stress Management eHealth Interventions. JMIR Research Protocols. 12. doi: 10.2196/47195. Full text in Research Archive Show summary

  Background: One-third or more of breast cancer survivors report stress and other psychological and physical complaints that can negatively impact their quality of life. Psychosocial stress management interventions, shown to mitigate the negative impact of these complaints, can now be delivered as accessible and convenient (for the patient and provider) eHealth interventions. In this randomized controlled trial (RCT), Coping After Breast Cancer (CABC), 2 modified versions of the stress management eHealth intervention program StressProffen were created: one with predominantly cognitive behavioral stress management content (StressProffen-cognitive behavioral therapy intervention [StressProffen-CBI]) and another with predominantly mindfulness-based stress management content (StressProffen-mindfulness-based intervention [StressProffen-MBI]). Objective: This study aims to investigate the effects in breast cancer survivors of using StressProffen-CBI and StressProffen-MBI compared with a control group (treatment as usual). Methods: Women diagnosed with breast cancer (stage I-III, unequivocally human epidermal growth factor receptor 2–positive or estrogen receptor-negative tumors) or ductal carcinoma in situ (DCIS) aged 21-69 years who completed the Cancer Registry of Norway–initiated health survey on quality of life are invited to the CABC trial about 7 months after diagnosis. Women who give consent to participate are randomized (1:1:1) to either the StressProffen-CBI, StressProffen-MBI, or control group. Both StressProffen interventions consist of 10 modules of stress management content delivered through text, sound, video, and images. The primary outcome is between-group changes in perceived stress at 6 months, assessed with Cohen 10-item Perceived Stress Scale. The secondary outcomes comprise changes in quality of life, anxiety, depression, fatigue, sleep, neuropathy, coping, mindfulness, and work-related outcomes approximately 1, 2, and 3 years after diagnosis. Long-term effects of the interventions on work participation, comorbidities, relapse or new cancers, and mortality will be assessed using data from national health registries. Results: Recruitment is scheduled from January 2021 to May 2023. The goal is to recruit 430 participants (100 in each group). As of April 14 2023, 428 participants have been enrolled. Conclusions: The CABC trial is possibly the largest ongoing psychosocial eHealth RCT in patients with breast cancer. If 1 or both interventions prove to be effective in reducing stress and improving psychosocial and physical complains, the StressProffen eHealth interventions could be beneficial, inexpensive, and easily implementable tools for breast cancer survivors when coping with late effects after cancer and cancer treatments.

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