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, 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

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.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Overview of the concept of molecular systemic relapse detection by analysis of liquid biopsies in the PBCB project. Blood and tumour samples are biobanked at diagnosis (1) and surgery (2). Blood samples continue to be drawn every 6 months for 11 years (3). The blood samples will allow for CTC, ctDNA, miRNA andmetabolite analysis (4). Following surgery and treatment, the serum level of ctDNA is too low for detection (5). At the time of macroscopic clinical or radiological detected relapse (6) the liquid biopsies (7) are carefully examined for various biomarkers. The findings are validated by examination of the primary tumour (2). Then, the previously drawn liquid biopsies (8) are carefully examined to find how many months ahead of the macroscopic relapse molecular biomarkers may be found in the liquid biopsies (9). The biomarkers in the liquid biopsies may be used to monitor the effect of secondary adjuvant treatment (10). Red dotted line: plasma level of the biomarker indicating systemic relapse in liquid biopsies. Green check mark, indicating that all systemic adjuvant treatments are initiated. CTC, circulating tumour cell; ctDNA, circulating tumour DNA; miRNA, micro-RNA; PBCB, Prospective Breast Cancer Biobank.
Figure 2
Figure 2
Overview of the study design (one armed observational study) and sampling protocol in the PBCB project. Number of patients at each study site lost to follow-up at each time point. =Completed; =Ongoing; FU, follow-up; HUH, Haukeland University Hospital; PBCB, Prospective Breast Cancer Biobank; PROM, patient-reported outcome measure; SUH, Stavanger University Hospital; TBC, to be conducted.

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