Sweden Cancerome Analysis Network - Breast : Genomic Profiling of Breast Cancer

Breast Neoplasms Clinical Trial

— SCAN-B  

Official title:

SCAN-B: The Sweden Cancerome Analysis Network - Breast Initiative

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02306096
• Other study ID #: SCANB001
• Status: Recruiting
• Start date: August 2010
• Est. completion date: August 2031

Study information

• Verified date: February 2024
• Source: Lund University
• Contact: Åke Borg, PhD
• Phone: +46-46-2752552
• Email: ake.borg[@]med.lu.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study evaluates the genomic profiles of breast cancer in a prospective and population-based manner. In the first phase, breast tumors are analyzed by whole transcriptome RNA-sequencing. Gene expression profiles, mutational profiles, and transcript isoform-level data will be analyzed in the context of patient information, clinicopathological variables, and outcome, with the purpose to develop new molecular diagnostic assays for breast cancer. Additional genome-scale RNA, DNA, and protein analyses will be performed in the future.

Description:

Breast cancer exhibits significant molecular, pathological, and clinical heterogeneity. Current patient and clinicopathological evaluation is imperfect for predicting outcome, which results in overtreatment for many patients, and for others, leads to death from recurrent disease. Therefore, additional criteria are needed to better personalize care and maximize treatment effectiveness and survival.

The Sweden Cancerome Analysis Network - Breast (SCAN-B) study was initiated in 2010 as a multicenter prospective population-based observational study with long-sighted aims to analyze breast cancers with next-generation genomic technologies for translational research and integrated with healthcare; decipher fundamental tumor biology from these analyses; utilize genomic data to develop and validate new clinically-actionable biomarker assays; and establish real-time clinical implementation of molecular diagnostic, prognostic, and predictive tests. In the first phase, we focus on molecular profiling by next-generation RNA-sequencing. Gene expression profiles, mutational profiles, and transcript isoform-level data will be analyzed in the context of patient information, clinicopathological variables, and outcome, with the purpose to develop new molecular diagnostic assays for breast cancer. Additional genome-scale RNA, DNA, and protein analyses will be performed in the future.

As of February 2024, over 20,000 patients have enrolled in the study, representing approximately 85% of all eligible patients within the catchment region. Tissue and blood collection is integrated within healthcare routines and clinical information is provided from national quality registries.

As of Q4 2021, the SCAN-B RNA-seq analysis for molecular subtyping and risk-of-recurrence has been clinically implemented for all breast cancer patients in Skåne within the Center for Molecular Diagnostics, Laboratory Medicine, Medical Service, Region Skåne.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20000
• Est. completion date: August 2031
• Est. primary completion date: August 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• suspicion or confirmed diagnosis of primary breast cancer

• signed informed consent

Exclusion Criteria:

• lack of signed informed consent

Related Conditions & MeSH terms

• Breast Neoplasms

Locations

Country	Name	City	State
Sweden	Hallands Hospital Halmstad	Halmstad
Sweden	Helsingborg Hospital	Helsingborg
Sweden	Kirurgiska kliniken	Jönköping
Sweden	Blekinge County Hospital	Karlskrona
Sweden	Central Hospital Kristianstad	Kristianstad
Sweden	Skåne University Hospital	Lund
Sweden	Skåne University Hospital	Malmö
Sweden	Uppsala University Hospital	Uppsala
Sweden	Central Hospital Växjö	Växjö

Sponsors (4)

Lead Sponsor	Collaborator
Lund University	Mrs. Berta Kamprad Foundation, South Sweden Breast Cancer Group, U-CAN

Country where clinical trial is conducted

Sweden, 

References & Publications (35)

Aine M, Boyaci C, Hartman J, Hakkinen J, Mitra S, Campos AB, Nimeus E, Ehinger A, Vallon-Christersson J, Borg A, Staaf J. Molecular analyses of triple-negative breast cancer in the young and elderly. Breast Cancer Res. 2021 Feb 10;23(1):20. doi: 10.1186/s — View Citation

Axelsson U, Ryden L, Johnsson P, Eden P, Mansson J, Hallberg IR, Borrebaeck CAK. A multicenter study investigating the molecular fingerprint of psychological resilience in breast cancer patients: study protocol of the SCAN-B resilience study. BMC Cancer. 2018 Aug 6;18(1):789. doi: 10.1186/s12885-018-4669-y. — View Citation

Bengtsson Y, Demircan K, Vallon-Christersson J, Malmberg M, Saal LH, Ryden L, Borg A, Schomburg L, Sandsveden M, Manjer J. Serum copper, zinc and copper/zinc ratio in relation to survival after breast cancer diagnosis: A prospective multicenter cohort stu — View Citation

Bjorklund SS, Aure MR, Hakkinen J, Vallon-Christersson J, Kumar S, Evensen KB, Fleischer T, Tost J; OSBREAC; Sahlberg KK, Mathelier A, Bhanot G, Ganesan S, Tekpli X, Kristensen VN. Subtype and cell type specific expression of lncRNAs provide insight into — View Citation

Brueffer C, Gladchuk S, Winter C, Vallon-Christersson J, Hegardt C, Hakkinen J, George AM, Chen Y, Ehinger A, Larsson C, Loman N, Malmberg M, Ryden L, Borg A, Saal LH. The mutational landscape of the SCAN-B real-world primary breast cancer transcriptome. — View Citation

Brueffer C, Vallon-Christersson J, Grabau D, Ehinger A, Hakkinen J, Hegardt C, Malina J, Chen Y, Bendahl PO, Manjer J, Malmberg M, Larsson C, Loman N, Ryden L, Borg A, Saal LH. Clinical Value of RNA Sequencing-Based Classifiers for Prediction of the Five — View Citation

Dahlgren M, George AM, Brueffer C, Gladchuk S, Chen Y, Vallon-Christersson J, Hegardt C, Hakkinen J, Ryden L, Malmberg M, Larsson C, Gruvberger-Saal SK, Ehinger A, Loman N, Borg A, Saal LH. Preexisting Somatic Mutations of Estrogen Receptor Alpha (ESR1) i — View Citation

Dalal H, Dahlgren M, Gladchuk S, Brueffer C, Gruvberger-Saal SK, Saal LH. Clinical associations of ESR2 (estrogen receptor beta) expression across thousands of primary breast tumors. Sci Rep. 2022 Mar 18;12(1):4696. doi: 10.1038/s41598-022-08210-3. — View Citation

Demircan K, Bengtsson Y, Chillon TS, Vallon-Christersson J, Sun Q, Larsson C, Malmberg M, Saal LH, Ryden L, Borg A, Manjer J, Schomburg L. Matched analysis of circulating selenium with the breast cancer selenotranscriptome: a multicentre prospective study — View Citation

Demircan K, Bengtsson Y, Sun Q, Brange A, Vallon-Christersson J, Rijntjes E, Malmberg M, Saal LH, Ryden L, Borg A, Manjer J, Schomburg L. Serum selenium, selenoprotein P and glutathione peroxidase 3 as predictors of mortality and recurrence following brea — View Citation

Demircan K, Sun Q, Bengtsson Y, Seemann P, Vallon-Christersson J, Malmberg M, Saal LH, Ryden L, Minich WB, Borg A, Manjer J, Schomburg L. Autoimmunity to selenoprotein P predicts breast cancer recurrence. Redox Biol. 2022 Jul;53:102346. doi: 10.1016/j.red — View Citation

Dihge L, Vallon-Christersson J, Hegardt C, Saal LH, Hakkinen J, Larsson C, Ehinger A, Loman N, Malmberg M, Bendahl PO, Borg A, Staaf J, Ryden L. Prediction of Lymph Node Metastasis in Breast Cancer by Gene Expression and Clinicopathological Models: Develo — View Citation

Fornvik D, Aaltonen KE, Chen Y, George AM, Brueffer C, Rigo R, Loman N, Saal LH, Ryden L. Detection of circulating tumor cells and circulating tumor DNA before and after mammographic breast compression in a cohort of breast cancer patients scheduled for n — View Citation

Glodzik D, Bosch A, Hartman J, Aine M, Vallon-Christersson J, Reutersward C, Karlsson A, Mitra S, Nimeus E, Holm K, Hakkinen J, Hegardt C, Saal LH, Larsson C, Malmberg M, Ryden L, Ehinger A, Loman N, Kvist A, Ehrencrona H, Nik-Zainal S, Borg A, Staaf J. C — View Citation

Gulis K, Ellbrant J, Svensjo T, Skarping I, Vallon-Christersson J, Loman N, Bendahl PO, Ryden L. A prospective cohort study identifying radiologic and tumor related factors of importance for breast conserving surgery after neoadjuvant chemotherapy. Eur J — View Citation

Larsson C, Ehinger A, Winslow S, Leandersson K, Klintman M, Dahl L, Vallon-Christersson J, Hakkinen J, Hegardt C, Manjer J, Saal L, Ryden L, Malmberg M, Borg A, Loman N. Prognostic implications of the expression levels of different immunoglobulin heavy ch — View Citation

Lundgren C, Bendahl PO, Borg A, Ehinger A, Hegardt C, Larsson C, Loman N, Malmberg M, Olofsson H, Saal LH, Sjoblom T, Lindman H, Klintman M, Hakkinen J, Vallon-Christersson J, Ferno M, Ryden L, Ekholm M. Agreement between molecular subtyping and surrogate — View Citation

Nacer DF, Vallon-Christersson J, Nordborg N, Ehrencrona H, Kvist A, Borg A, Staaf J. Molecular characteristics of breast tumors in patients screened for germline predisposition from a population-based observational study. Genome Med. 2023 Apr 14;15(1):25. — View Citation

Nilsson MP, Emmertz M, Kristoffersson U, Borg A, Larsson C, Rehn M, Winter C, Saal LH, Brandberg Y, Loman N. Germline mutations in BRCA1 and BRCA2 incidentally revealed in a biobank research study: experiences from re-contacting mutation carriers and rela — View Citation

Nilsson MP, Winter C, Kristoffersson U, Rehn M, Larsson C, Saal LH, Loman N. Efficacy versus effectiveness of clinical genetic testing criteria for BRCA1 and BRCA2 hereditary mutations in incident breast cancer. Fam Cancer. 2017 Apr;16(2):187-193. doi: 10 — View Citation

Persson H, Sokilde R, Hakkinen J, Pirona AC, Vallon-Christersson J, Kvist A, Mertens F, Borg A, Mitelman F, Hoglund M, Rovira C. Frequent miRNA-convergent fusion gene events in breast cancer. Nat Commun. 2017 Oct 5;8(1):788. doi: 10.1038/s41467-017-01176- — View Citation

Persson H, Sokilde R, Hakkinen J, Vallon-Christersson J, Mitelman F, Borg A, Hoglund M, Rovira C. Analysis of fusion transcripts indicates widespread deregulation of snoRNAs and their host genes in breast cancer. Int J Cancer. 2020 Jun 15;146(12):3343-335 — View Citation

Ryden L, Loman N, Larsson C, Hegardt C, Vallon-Christersson J, Malmberg M, Lindman H, Ehinger A, Saal LH, Borg A. Minimizing inequality in access to precision medicine in breast cancer by real-time population-based molecular analysis in the SCAN-B initiative. Br J Surg. 2018 Jan;105(2):e158-e168. doi: 10.1002/bjs.10741. — View Citation

Saal LH, Vallon-Christersson J, Hakkinen J, Hegardt C, Grabau D, Winter C, Brueffer C, Tang MH, Reutersward C, Schulz R, Karlsson A, Ehinger A, Malina J, Manjer J, Malmberg M, Larsson C, Ryden L, Loman N, Borg A. The Sweden Cancerome Analysis Network - Br — View Citation

Saghir H, Veerla S, Malmberg M, Ryden L, Ehinger A, Saal LH, Vallon-Christersson J, Borg A, Hegardt C, Larsson C, Haidar A, Hedenfalk I, Loman N, Kimbung S. How Reliable Are Gene Expression-Based and Immunohistochemical Biomarkers Assessed on a Core-Needl — View Citation

Sartor H, Zackrisson S, Hegardt C, Larsson C. "Association of mammographic features with molecular breast tumor profiles". Cancer Treat Res Commun. 2021;28:100387. doi: 10.1016/j.ctarc.2021.100387. Epub 2021 May 9. — View Citation

Sharma A, Weitz P, Wang Y, Liu B, Vallon-Christersson J, Hartman J, Rantalainen M. Development and prognostic validation of a three-level NHG-like deep learning-based model for histological grading of breast cancer. Breast Cancer Res. 2024 Jan 29;26(1):17 — View Citation

Sigurjonsdottir G, De Marchi T, Ehinger A, Hartman J, Bosch A, Staaf J, Killander F, Nimeus E. Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established — View Citation

Sokilde R, Persson H, Ehinger A, Pirona AC, Ferno M, Hegardt C, Larsson C, Loman N, Malmberg M, Ryden L, Saal L, Borg A, Vallon-Christerson J, Rovira C. Refinement of breast cancer molecular classification by miRNA expression profiles. BMC Genomics. 2019 — View Citation

Staaf J, Glodzik D, Bosch A, Vallon-Christersson J, Reutersward C, Hakkinen J, Degasperi A, Amarante TD, Saal LH, Hegardt C, Stobart H, Ehinger A, Larsson C, Ryden L, Loman N, Malmberg M, Kvist A, Ehrencrona H, Davies HR, Borg A, Nik-Zainal S. Whole-genom — View Citation

Staaf J, Hakkinen J, Hegardt C, Saal LH, Kimbung S, Hedenfalk I, Lien T, Sorlie T, Naume B, Russnes H, Marcone R, Ayyanan A, Brisken C, Malterling RR, Asking B, Olofsson H, Lindman H, Bendahl PO, Ehinger A, Larsson C, Loman N, Ryden L, Malmberg M, Borg A, — View Citation

Vallon-Christersson J, Hakkinen J, Hegardt C, Saal LH, Larsson C, Ehinger A, Lindman H, Olofsson H, Sjoblom T, Warnberg F, Ryden L, Loman N, Malmberg M, Borg A, Staaf J. Cross comparison and prognostic assessment of breast cancer multigene signatures in a — View Citation

Veerla S, Hohmann L, Nacer DF, Vallon-Christersson J, Staaf J. Perturbation and stability of PAM50 subtyping in population-based primary invasive breast cancer. NPJ Breast Cancer. 2023 Oct 19;9(1):83. doi: 10.1038/s41523-023-00589-0. — View Citation

Wang Y, Ali MA, Vallon-Christersson J, Humphreys K, Hartman J, Rantalainen M. Transcriptional intra-tumour heterogeneity predicted by deep learning in routine breast histopathology slides provides independent prognostic information. Eur J Cancer. 2023 Sep — View Citation

Winter C, Nilsson MP, Olsson E, George AM, Chen Y, Kvist A, Torngren T, Vallon-Christersson J, Hegardt C, Hakkinen J, Jonsson G, Grabau D, Malmberg M, Kristoffersson U, Rehn M, Gruvberger-Saal SK, Larsson C, Borg A, Loman N, Saal LH. Targeted sequencing o — View Citation

* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biomarkers and clinicopathological information	Analysis of genomic data (biomarkers) and their relationship to patient and tumor clinicopathological information; assessment of analytical validity.	up to 20-years
Primary	Invasive disease-free survival	Different biomarkers will be analysed in the context of invasive disease-free survival (IDFS) at different time-points for different subgroups of the prospective cohort, for example for all patients receiving a particular therapy or patients with tumors of a specific molecular subtype.	up to 20-years
Secondary	Overall survival	Different biomarkers will be analysed in the context of overall survival (OS) at different time-points for different subgroups of the prospective cohort, for example for all patients receiving a particular therapy or patients with tumors of a specific molecular subtype.	3-years, 5-years, 10-years, 15-years, 20-years
Secondary	Breast cancer-specific survival	Different biomarkers will be analysed in the context of breast cancer survival (BCS) at different time-points for different subgroups of the prospective cohort, for example for all patients receiving a particular therapy or patients with tumors of a specific molecular subtype.	3-years, 5-years, 10-years, 15-years, 20-years
Secondary	Pathological response	Different biomarkers will be analysed in the context of pathological response at time of surgery for patients receiving pre-operative therapy.	intraoperative

External Links

•   Sweden Cancerome Analysis Network - Breast (SCAN-B) Website (Lund University) [SWEDISH LANGUAGE]