Impact of race and ethnicity on outcomes in patients with hormone receptor-positive breast cancer treated with CDK4/6 inhibitors

种族和民族对接受 CDK4/6 抑制剂治疗的激素受体阳性乳腺癌患者预后的影响

• 批准号: 10762267
• 负责人: Benny Abraham Kaipparettu
• 金额: $ 4万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-21 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10762267
• 关键词: Address; Adherence; Affect; African American; American; Atlases; Awareness; Breast Cancer Patient; Breast Cancer Treatment; Breast Cancer cell line; Breast Cancer therapy; CDK4 gene; Cancer Etiology; Cessation of life; Clinical; Code; Computer Models; Data; Databases; Death Rate; Decision Making; Disparity; Documentation; Drug resistance pathway; Early Diagnosis; Education; Electronic Health Record; Environmental Risk Factor; Epidermal Growth Factor Receptor; Epigenetic Process; Ethnic Origin; European; FAT gene; Female Breast Carcinoma; Financial Hardship; Frequencies; Genes; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genomics; Head and Neck Cancer; Hispanic; Hispanic Populations; Human; In Vitro; Interview; Malignant Neoplasms; Messenger RNA; Metastatic breast cancer; Mutation; Not Hispanic or Latino; Oral; Outcome; Patients; Pattern; Pharmaceutical Preparations; Population; Population Study; Prevalence; Progression-Free Survivals; Quality of life; RB1 gene; Race; Resistance; Resistance development; Social support; Surveys; Testing; The Cancer Genome Atlas; Treatment outcome; United States; Variant; Woman; anticancer research; cancer genomics; design; differential expression; genomic data; hormone receptor-positive; hormone therapy; improved; individual patient; information gathering; inhibitor; inhibitor therapy; mRNA Expression; malignant breast neoplasm; markov model; medication compliance; mortality; novel therapeutic intervention; outcome disparities; patient population; racial disparity; resistance mechanism; screening; side effect; social determinants; social health determinants; statistics; targeted treatment; therapy resistant; treatment site; tumor; verbal; Address; Adherence; Affect; African American; American; Atlases; Awareness; Breast Cancer Patient; Breast Cancer Treatment; Breast Cancer cell line; Breast Cancer therapy; CDK4 gene; Cancer Etiology; Cessation of life; Clinical; Code; Computer Models; Data; Databases; Death Rate; Decision Making; Disparity; Documentation; Drug resistance pathway; Early Diagnosis; Education; Electronic Health Record; Environmental Risk Factor; Epidermal Growth Factor Receptor; Epigenetic Process; Ethnic Origin; European; FAT gene; Female Breast Carcinoma; Financial Hardship; Frequencies; Genes; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genomics; Head and Neck Cancer; Hispanic; Hispanic Populations; Human; In Vitro; Interview; Malignant Neoplasms; Messenger RNA; Metastatic breast cancer; Mutation; Not Hispanic or Latino; Oral; Outcome; Patients; Pattern; Pharmaceutical Preparations; Population; Population Study; Prevalence; Progression-Free Survivals; Quality of life; RB1 gene; Race; Resistance; Resistance development; Social support; Surveys; Testing; The Cancer Genome Atlas; Treatment outcome; United States; Variant; Woman; anticancer research; cancer genomics; design; differential expression; genomic data; hormone receptor-positive; hormone therapy; improved; individual patient; information gathering; inhibitor; inhibitor therapy; mRNA Expression; malignant breast neoplasm; markov model; medication compliance; mortality; novel therapeutic intervention; outcome disparities; patient population; racial disparity; resistance mechanism; screening; side effect; social determinants; social health determinants; statistics; targeted treatment; therapy resistant; treatment site; tumor; verbal

Breast cancer (BC) is the most common cancer in women worldwide and is the second leading cause of cancer death in women. However, the advances in outcomes of BC patients have been limited to a subset of the affected population, namely European American (EA) women compared to their African American (AA) women counterparts. Despite various hormone therapies, the hormone receptor (ER/PR) positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/Her2-) subtype of BC remains difficult to treat. Cyclin- dependent kinase 4 and 6 inhibitors (CDK4/6i) have recently emerged as a new treatment strategy. Interestingly a 2022 population-based study confirmed that while the outcomes for HR+/Her2- metastatic BC have improved since CDK4/6i were introduced in 2015, this effect is primarily driven by the improved overall survival (OS) in non-Hispanic EA patients, without significant improvement in AA or Hispanics patients. The relative contribution of genetic factors vs. medication adherence or social determinants of health (SDOH) on such outcomes is less understood. Recent efforts to address this gap include databases such as ‘All of Us’, designed to better understand the interplay between genetic factors and social determinants. From a functional point, our preliminary analysis of The Cancer Genomic Atlas (TCGA) data shows decreased mRNA expression of FAT1, FAT4 and RB1, the major genes involved in resistance to CDK4/6i, in AA compared to EA HR+/Her2- BC. Thus, this project will do preliminary analysis of two aspects of BC therapy resistance in AA BC patients. Aim-1 of this project will assess the impact of medication adherence and various social determinants on clinical outcomes of female BC patients treated with CDK4/6i. Aim-2 will analyze the impact of genetic variations and low expression of FAT1, FAT4 and RB1 genes on the development of resistance to CDK4/6i in AA women with BC. We will use surveys, verbal medication review and EHR documentation of medication possession to gather information related to medication adherence and social determinants that may impact compliance. We will also analyze the prevalence of germline and somatic variations and epigenetic status of FAT1, FAT4 and RB1 genes in BC patients of EA and non-EA ancestry. Using computational modeling, we will predict the functional networking of FAT1, FAT4 and RB1 low expression in AA BC patients. Using established databases, clinical information obtained from the electronic health record (EHR), and surveys exploring SDOH and medication adherence patterns, this pilot aims to generate preliminary data exploring the impact of these factors on treatment outcomes in AA vs. EA patients receiving oral targeted therapy, including CDK4/6i. Discovery of AA-centric genetic variations and the impact of low expressed FAT1, FAT4 and RB1 genes in the functional networking will be critical in pre-selecting AA BC patients that may benefit from CDK4/6i therapy.

乳腺癌（BC）是全球女性最常见的癌症，是癌症的第二主要原因 女性死亡。但是，卑诗省患者结果的进展仅限于受影响的一部分 与非裔美国人（AA）妇女相比，人口，即欧美（EA）妇女 同行。尽管有多种骑马疗法，但骑马受体（ER/PR）阳性（HR+），人类 BC的表皮生长因子受体2（HER2）阴性（HR+/HER2-）亚型仍然很难治疗。细胞周期蛋白 依赖性激酶4和6抑制剂（CDK4/6i）最近成为一种新的治疗策略。 有趣的是 一项基于2022人群的研究证实，尽管HR+/HER2-转移性BC的结果有所改善 由于CDK4/6i于2015年引入CDK4/6i，因此这种效果主要是由改善的总体生存（OS）驱动 非西班牙裔EA AA或西班牙裔患者没有显着改善的患者。 相对贡献 遗传因素与药物依从性或健康结果的社会决定者（SDOH）在此结果上较少 理解。解决这一差距的最新努力包括诸如“我们所有人”之类的数据库，旨在更好 了解遗传因素和社会决定者之间的相互作用。从功能上，我们的 初步分析 癌症基因组图集（TCGA）数据显示，FAT1的mRNA表达降低 与EA HR+/HER2-BC相比，AA中涉及CDK4/6i抗性的主要基因FAT4和RB1。 那， 该项目将对AA BC患者的BC治疗耐药性的两个方面进行初步分析。目标的目标 项目将评估药物依从性和各种社会决定者对临床结果的影响 接受CDK4/6i治疗的女性BC患者。 AIM-2将分析遗传变异和低表达的影响 AA女性BC妇女对CDK4/6i的抗性发展的FAT1，FAT4和RB1基因。我们将使用 调查，言语药物审查和EHR药物潜力的文档以收集信息 与可能影响合规性的药物依从性和社会决定者有关。我们还将分析 卑诗 EA和非AEA祖先的患者。使用计算建模，我们将预测 AA BC患者的FAT1，FAT4和RB1低表达。使用已建立的数据库，临床信息 从电子健康记录（EHR）获得，调查探索SDOH和药物依从性 模式，该试点旨在生成初步数据，以探讨这些因素对治疗结果的影响 在接受口服靶向疗法的AA与EA患者中，包括CDK4/6i。发现以AA为中心的通用 低表达FAT1，FAT4和RB1基因在功能网络中的变化和影响将是 对于可能受益于CDK4/6i治疗的预选AA BC患者至关重要。