Brockton Nigel T, Gill Stephanie J, Laborge Stephanie L, Paterson Alexander H G, Cook Linda S, Vogel Hans J, Shemanko Carrie S, Hanley David A, Magliocco Anthony M, Friedenreich Christine M
Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Room 515C, Holy Cross Centre, 2210 2nd St, SW, Calgary, AB, T2S 3C3, Canada.
Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
BMC Cancer. 2015 Jul 10;15:512. doi: 10.1186/s12885-015-1528-y.
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.
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.
骨是乳腺癌远处转移最常见的部位,50% - 70%发生转移的患者会受到影响。尽管进行了数十年的有益研究,但对这些病变的有效预防、预测和治疗仍然难以实现。乳腺癌骨转移(B2B)研究项目包括一组乳腺癌初发患者的前瞻性队列以及四个子项目,这些子项目正在研究乳腺癌骨转移的重点领域。其中包括生活方式因素和炎症对骨转移风险的影响、原发肿瘤的基因表达特征、代谢组学在早期检测骨转移性疾病中的潜在作用以及驱动骨转移病变的信号通路。
方法/设计:B2B研究项目正在加拿大艾伯塔省招募一组600名新诊断的、初发的、I - IIIc期乳腺癌幸存者的前瞻性队列,为期五年。在基线时,收集治疗前/手术前的血样,并通过面对面访谈和自行填写问卷收集详细的流行病学数据。在指定的随访间隔(24、48和72个月)完成额外的自行填写问卷和血样采集。每次随访前通过与艾伯塔癌症登记处的记录链接获取生命状态。通过病历摘要确定复发情况。四个项目中的每一个都应用特定的方法和分析来评估血清维生素D和细胞因子浓度、肿瘤转录本和蛋白质表达、血清代谢组学谱以及体外细胞信号传导对乳腺癌骨转移的影响。
B2B研究项目将解决乳腺癌骨转移的关键问题,包括生活方式因素(特别是对维生素D状态的全面评估)、炎症与骨转移之间的关联,原发肿瘤基因表达在组织嗜性中的意义,代谢组学谱在风险评估和早期检测中的潜力,以及控制转移肿瘤微环境的信号通路。这四个项目之间有很大的协同作用,希望这个综合研究项目能增进我们对乳腺癌骨转移关键方面的理解,以改善这些病变的预防、预测、检测和治疗。