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

Abstract

BackgroundBone 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/DesignThe 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.DiscussionThe 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.

Bone metastasis risk factors in breast cancer

“…More recently, Hoshino et al , demonstrated that tumour exosome integrins prepare a favourable microenvironment at future metastatic sites and mediate non-random patterns of metastasis [ 29 ]. Thereby BC metastasis organotropism, tumour-microenvironment interactions, and strategies to address them for prevention and treatment of BM are areas of intense investigation [ 30 , 31 ]…”

Daily Oral Ibandronate With Adjuvant Endocrine Therapy in Postmenopausal Women With Estrogen Receptor–Positive Breast Cancer (BOOG 2006-04): Randomized Phase III TEAM-IIB Trial

“…1 Because hormone receptor–positive breast cancer cells prefer an osseous microenvironment, about 70% of breast cancer metastases are bone recurrences. 2,3 Nitrogen-containing bisphosphonates such as ibandronate affect bone metabolism by inhibiting key enzymes of the intracellular mevalonate pathway. 4 This decreases osteoclast-mediated bone resorption and osteoclast survival, causing an increase in bone density and a decreased release of cytokines and growth factors.…”

Prospective comparison of the diagnostic accuracy of 18F-FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients

“…Despite the advances in the treatment of breast cancer, up to 30% of patients still develop distant metastases over the course of the disease [3]. Herein, the skeleton is the most frequent site of distant metastases in breast cancer patients, accounting for 50-70% of all metastases [3][4][5][6][7]. The affection of the bone can cause various complications such as pain, pathological fractures, spinal cord compression, and hypercalcemia, which often have a major impact on patients' morbidity and mortality [8][9][10].…”