The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer

Abstract

Background: Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone.

Methods/design: The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases.

Discussion: The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the potential of metabolomic profiles for risk assessment and early detection and the signalling pathways controlling the metastatic tumour microenvironment. There is substantial synergy between the four projects and it is hoped that this integrated program of research will advance our understanding of key aspects of bone metastases from breast cancer to improve the prevention, prediction, detection, and treatment of these lesions.

Fig. 1

B2B Research Program overview. Clinical data, questionnaire and interview responses, and biospecimens collected from the B2B Cohort are used to support each of the four Core Projects

Fig. 2

B2B Research Program timeline. Recruitment for the B2B Cohort began in 2010, and steadily increased through successive operational enhancements, key partnerships, and implementation of a centralized biospecimen ascertainment infrastructure

Fig. 3

Ascertainment recruitment, data and biospecimen collection and sharing scheme. Newly diagnosed cancer patients are identified through the ACR, and are invited to donate biospecimen samples by the ACRB utilizing the CoBRA infrastructure. Clinical data and biospecimens are stored by the ACRB, and contact information from eligible and consenting participants is sent to study coordinators of relevant research programs. Subsequent blood samples and blood questionnaire data for routine study follow-up are collected by the ACRB and act as a shared resource between the biorepository and research study team

Fig. 4

B2B/AMBER participant recruitment. Eligible patients are identified by the ACRB through CoBRA processes, and the contact details of consenting biospecimen donors are sent to a recruitment database shared by both the AMBER and B2B study coordinators. Patients are invited to participate by each study, and if they agree, their information is then imported into the specific study database. Some information sharing occurs between the AMBER and B2B study database, such as whether or not shared questionnaires have been completed