Liquid biopsies and patient-reported outcome measures for integrative monitoring of patients with early-stage breast cancer: a study protocol for the longitudinal observational Prospective Breast Cancer Biobanking (PBCB) study

Håvard Søiland; Emiel A M Janssen; Thomas Helland; Finn Magnus Eliassen; Magnus Hagland; Oddmund Nordgård; Siri Lunde; Tone Hoel Lende; Jørn Vegard Sagen; Kjersti Tjensvoll; Bjørnar Gilje; Kristin Jonsdottir; Einar Gudlaugsson; Kirsten Lode; Kari Britt Hagen; Birgitta Haga Gripsrud; Ragna Lind; Anette Heie; Turid Aas; Marie Austdal; Nina Gran Egeland; Tomm Bernklev; Timothy L Lash; Linn Skartveit; Ann Cathrine Kroksveen; Satu Oltedal; Jan Terje Kvaløy; Ernst A Lien; Linda Sleire; Gunnar Mellgren; PBCB-study group

doi:10.1136/bmjopen-2021-054404

Liquid biopsies and patient-reported outcome measures for integrative monitoring of patients with early-stage breast cancer: a study protocol for the longitudinal observational Prospective Breast Cancer Biobanking (PBCB) study

BMJ Open. 2022 Apr 29;12(4):e054404. doi: 10.1136/bmjopen-2021-054404.

Authors

Håvard Søiland^{1

2}, Emiel A M Janssen^{3

4}, Thomas Helland^{2

5}, Finn Magnus Eliassen⁶, Magnus Hagland^{2

5}, Oddmund Nordgård^{7

8}, Siri Lunde⁶, Tone Hoel Lende⁶, Jørn Vegard Sagen^{2

5}, Kjersti Tjensvoll⁷, Bjørnar Gilje⁹, Kristin Jonsdottir¹⁰, Einar Gudlaugsson³, Kirsten Lode^{10

11}, Kari Britt Hagen¹², Birgitta Haga Gripsrud¹¹, Ragna Lind^{13

14}, Anette Heie¹², Turid Aas¹², Marie Austdal^{3

10}, Nina Gran Egeland⁶, Tomm Bernklev^{15

16}, Timothy L Lash¹⁷, Linn Skartveit⁵, Ann Cathrine Kroksveen¹⁸, Satu Oltedal⁷, Jan Terje Kvaløy^{10

19}, Ernst A Lien², Linda Sleire⁵, Gunnar Mellgren^{2

18}; PBCB-study group

Affiliations

¹ Department of Breast and Endocrine Surgery, Stavanger University Hospital, Stavanger, Norway hsoiland@gmail.com.
² Department of Clinical Science, University of Bergen, Bergen, Norway.
³ Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
⁴ Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger, Norway.
⁵ Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.
⁶ Department of Breast and Endocrine Surgery, Stavanger University Hospital, Stavanger, Norway.
⁷ Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway.
⁸ Department of Chemistry, Bioscience, University of Stavanger, Stavanger, Norway.
⁹ Department of Oncology, Stavanger University Hospital, Stavanger, Norway.
¹⁰ Department of Research, Stavanger University Hospital, Stavanger, Norway.
¹¹ Faculty of Health Sciences Department of Caring and Ethics, University of Stavanger, Stavanger, Norway.
¹² Department of Breast and Endocrine Surgery, Haukeland University Hospital, Bergen, Norway.
¹³ Department of Medicine, Haukeland University Hospital, Bergen, Norway.
¹⁴ Department of Clinical Medicine, University of Bergen, Bergen, Norway.
¹⁵ Central Hospital in Vestfold, Tønsberg, Norway.
¹⁶ Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁷ Department of Epidemiology, Emory University, Atlanta, Georgia, USA.
¹⁸ Laboratory Medicine and Pathology, Haukeland University Hospital, Bergen, Norway.
¹⁹ Mathematics and Physics, Department of Mathematics and Natural Science, University of Stavanger, Stavanger, Norway.

Abstract

Introduction: Breast cancer is still the most common malignancy among women worldwide. The Prospective Breast Cancer Biobank (PBCB) collects blood and urine from patients with breast cancer every 6 or 12 months for 11 years from 2011 to 2030 at two university hospitals in Western Norway. The project aims to identify new biomarkers that enable detection of systemic recurrences at the molecular level. As blood represents the biological interface between the primary tumour, the microenvironment and distant metastases, liquid biopsies represent the ideal medium to monitor the patient's cancer biology for identification of patients at high risk of relapse and for early detection systemic relapse.Including patient-reported outcome measures (PROMs) allows for a vast number of possibilities to compare PROM data with biological information, enabling the study of fatigue and Quality of Life in patients with breast cancer.

Methods and analysis: A total of 1455 patients with early-stage breast cancer are enrolled in the PBCB study, which has a one-armed prospective observational design. Participants consent to contribute liquid biopsies (i.e., peripheral blood and urine samples) every 6 or 12 months for 11 years. The liquid biopsies are the basis for detection of circulating tumour cells, circulating tumour DNA (ctDNA), exosomal micro-RNA (miRNA), miRNA in Tumour Educated Platelet and metabolomic profiles. In addition, participants respond to 10 PROM questionnaires collected annually. Moreover, a control group comprising 200 women without cancer aged 25-70 years will provide the same data.

Ethics and dissemination: The general research biobank PBCB was approved by the Ministry of Health and Care Services in 2007, by the Regional Ethics Committee (REK) in 2010 (#2010/1957). The PROM (#2011/2161) and the biomarker study PerMoBreCan (#2015/2010) were approved by REK in 2011 and 2015 respectively. Results will be published in international peer reviewed journals. Deidentified data will be accessible on request.

Trial registration number: NCT04488614.

Keywords: Breast surgery; Breast tumours; Cell biology; MOLECULAR BIOLOGY; Pathology.

Publication types

Clinical Trial Protocol

MeSH terms

Adult
Aged
Biological Specimen Banks
Biomarkers
Breast Neoplasms* / diagnosis
Female
Humans
Liquid Biopsy
MicroRNAs*
Middle Aged
Neoplasm Recurrence, Local
Observational Studies as Topic
Patient Reported Outcome Measures
Prospective Studies
Quality of Life
Tumor Microenvironment

Substances

Biomarkers
MicroRNAs

Associated data

ClinicalTrials.gov/NCT04488614