Diabetes, Metformin and Breast Cancer Prognosis

简介（由申请人提供）：糖尿病和癌症是影响全球健康的常见疾病。许多研究表明，糖尿病与乳腺癌患者较高的总死亡率有关。然而，目前尚不清楚的是，与非糖尿病患者相比，患有糖尿病的乳腺癌患者的总体死亡率较高，是否与乳腺癌预后较差有关，与心血管疾病等其他原因有关，还是与乳腺癌的不同管理有关，包括肿瘤特征和治疗选择。此外，广泛用于2型糖尿病一线治疗的口服药物二甲双胍也在考虑用于非糖尿病癌症患者作为辅助治疗。然而，在以人群为基础的环境中，尚无研究考察其对癌症预后的潜在影响。回答这些问题将对糖尿病管理和癌症治疗产生直接影响，以改善女性糖尿病患者的乳腺癌预后，并对这些患者的适当护理至关重要。我们将使用来自妇女健康倡议（WHI）的数据，这是一项大型前瞻性队列研究，以评估既往糖尿病（特定目标1）和糖尿病治疗，特别是二甲双胍（特定目标2）对乳腺癌患者预后的影响。这是第一个使用成熟队列来解决这些问题的前瞻性研究。妇女健康倡议包括关于人口和社会心理特征、乳腺癌筛查、乳腺癌风险因素、糖尿病药物治疗、由医生判定并使用SEER协议编码的肿瘤特征以及由医生判定的死亡原因的详细和全面的数据。我们希望提出的分析能够促进对既往糖尿病和糖尿病治疗是否以及如何影响乳腺癌患者生存的理解。此外，本研究中使用的新分析和方法可以在未来扩展到与糖尿病或其他合并症相关的其他类型癌症的更全面的检查。此外，这个项目将提供很好的机会，让学生接触研究，激发他们在学术领域追求事业的兴趣。

DESCRIPTION (provided by applicant): Diabetes and cancer are common diseases that have a tremendous impact on health worldwide. A number of studies have indicated that diabetes is associated with higher overall mortality in patients with breast cancer. However, it is unclear whether the higher overall mortality seen in breast cancer patients with diabetes compared to those without diabetes is related to a poorer breast cancer prognosis, to other causes such as cardiovascular disease, or to different management of breast cancer, including tumor characteristics and treatment choices. In addition, metformin, an oral drug widely used as a first-line therapy for type 2 diabetes, is also under consideration for use in non-diabetic cancer patients as an adjunctive therapy. However, there is no study examining its potential effect on cancer prognosis in a population-based setting. Answering these questions will have direct influence on diabetes management and cancer treatment to improve breast cancer outcomes for women with diabetes and is critical to inform the proper care of these patients. We will use data from the Women's Health Initiative (WHI), a large prospective cohort study, to assess influence of pre-existing diabetes (specific aim 1) and diabetes treatment, particularly metformin (specific aim 2), on prognosis of patients with breast cancer. This is the first prospective study o use a well-established cohort to address these questions. The Women's Health Initiative includes detailed and comprehensive data on demographic and psychosocial characteristics, breast cancer screening, breast cancer risk factors, diabetes medication treatments, tumor characteristics that are physician-adjudicated and coded using SEER protocols and physician-adjudicated causes of death. We expect the proposed analyses to advance understanding of whether and how pre-existing diabetes and diabetes treatment influences survival following breast cancer. In addition, the novel analyses and methods used for this study can be expanded in the future to a more comprehensive examination of other types of cancer in relation to diabetes or other co-morbidities. Additionally, this project will provide great opportunities for exposing students to research and stimulating their interests in pursuing careers in academic fields.