Project 1-Immunogenomic diversity in triple negative breast cancer health disparities

摘要-项目1 路易斯安那州三阴性乳腺癌(TNBC)的发病率是全国最高的之一， 尤其是在非裔美国人(AA)女性中。再障女性患肥胖症的风险也很高。 欧美(EA)。这些明显分离的疾病可能与遗传学、表观遗传学和 慢性炎症。TNBC是一组遗传上不同的疾病，包括多个分子 基于转录表达和体细胞突变的亚型。这些子类型对 标准化疗，但尚未在临床实践中常规使用，尚不清楚它们在治疗再生障碍性贫血方面有多好 病人。我们的初步数据和文献表明，分子签名以及炎性细胞 T细胞侵袭TNBC可提供重要的预后信息。作为P20计划的一部分 ，我们将探索种族、血统、肿瘤分子肖像和 路易斯安那州TNBC患者的免疫生物标志物以及肥胖在修饰中的可能作用 肿瘤免疫。具体地说，我们希望：1)追溯确定分子肖像是否 EA和AA患者的TNBC和/或免疫生物标记物的表达不同，并且 肥胖是否与不利的免疫生物标志物相关，不分种族和2) 前瞻性地描述和比较基因组和免疫学特征以及对 EA与AA、肥胖与非肥胖患者的II/II期TNBC肿瘤的新辅助治疗 肥胖，以及未实现聚合酶链式反应的病例的治疗前和治疗后样本。这些数据将 为开发适用于再生障碍性贫血患者的新的临床可操作生物标志物提供基础 TNBC和常见的合并症，如肥胖。此外，这些数据还可用于为决策提供信息 关于预防战略，并优化对服务不足的患者的治疗。作为新的治疗方法，如 随着免疫疗法成为治疗库的一部分，我们的数据将成为假设驱动的基础 在我们的患者群体中进行临床信息生物标记物的研究。

ABSTRACT- Project 1 The incidence of triple-negative breast cancer (TNBC) in Louisiana is among the highest in the nation, particularly among African American (AA) women. AA women are also at high risk of obesity compared to European-American (EA). These apparently separate conditions may be linked by genetics, epigenetics and chronic inflammation. TNBC is a genetically heterogeneous group of diseases that includes multiple molecular subtypes based on transcript expression and somatic mutations. These subtypes respond differently to standard chemotherapy but are not yet routinely in clinical practice and it is unknown how well they apply to AA patients. Our preliminary data and the literature show that molecular signatures as well as inflammatory cells and T cells infiltrating TNBC may provide important prognostic information. As a part of this P20 Planning Grant project, we will explore the relationships between race, ancestry, tumor molecular portraits and immunological biomarkers in TNBC patients from Louisiana, as well as the possible role of obesity in modifying tumor immunity. Specifically, we wish to: 1) Retrospectively determine whether the molecular portraits of TNBC and/or the expression of immunological biomarkers differ between EA and AA patients, and whether obesity is associated with unfavorable immunological biomarkers irrespective of race and 2) Prospectively characterize and compare genomic and immunological portraits and response to neoadjuvant treatment of stage II/II TNBC tumors from EA versus AA patients, obese versus non- obese, and pre- versus post-treatment samples in cases that do not achieve pCR. These data will provide the basis for the development of novel clinically actionable biomarkers applicable to AA patients with TNBC and common comorbidities such as obesity. Additionally, this data can be used to inform decisions regarding prevention strategies, and to optimize treatment for underserved patients. As novel treatments such as immunotherapy become part of the therapeutic arsenal, our data will form the basis for hypothesis-driven studies of clinically informative biomarkers in our patient population.