Novel predictors of survival among breast cancer patients with/without HIV in South Africa

南非感染/未感染艾滋病毒的乳腺癌患者生存的新预测因素

基本信息

批准号：
10615640
负责人：
Herbert Cubasch
金额：
$ 34.72万
依托单位：
WITS HEALTH CONSORTIUM (PTY), LTD
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10615640
关键词：
Academic Medical Centers Achievement Address Adherence Affect Africa South of the Sahara African ancestry Age Blood specimen Breast Breast Cancer Patient Breast Cancer Treatment Budgets CYP2D6 gene Cancer Etiology Cancer Patient Carcinoma Cessation of life Characteristics Chemotherapy-Oncologic Procedure Chronic Clinic Clinical Collaborations Contracts Data Development Diagnosis Disease Dose Drug Interactions Drug Kinetics Enrollment Enzyme Inhibition Enzymes Female Funding Genetic Polymorphism Genotype Good Clinical Practice Grant HIV HIV Infections HIV Seronegativity HIV Seropositivity Hospitals Incidence Individual Informed Consent Life Expectancy Link Liver Malignant Neoplasms Mediator Mentors Metabolism Modality Monitor Mortality Determinants Natural History Newly Diagnosed Oral Outcome Outcome Study Patient Self-Report Patient-Focused Outcomes Patients Pharmaceutical Preparations Pharmacogenomics Plasma Polypharmacy Postdoctoral Fellow Predisposition Preparation Prevalence Prognosis Prospective Studies Publications Reporting Research Ethics Research Personnel Resources Serum South Africa South African Specimen Standardization Students Surrogate Markers Surveys Survival Rate Tamoxifen Toxic effect Training Treatment Efficacy Universities Viral Load result Wit Woman Work Zimbabwe adjuvant endocrine therapy antiretroviral therapy black women breast cancer diagnosis breast cancer survival cancer health disparity cancer therapy chemotherapy cohort comorbidity compliance behavior doctoral student epidemiology study evidence based guidelines gene interaction hormone therapy human old age (65+)improved insight lectures low and middle-income countries malignant breast neoplasm middle age mortality multi-ethnic neighborhood disadvantage novel premature recruit sarcopenia sociodemographics survival prediction therapy adherence treatment adherence treatment and outcome

项目摘要

SUMMARY: Novel predictors of survival among breast cancer patients with/without HIV in South Africa As antiretroviral therapy (ART) improves survival among HIV-infected individuals, they become susceptible to diseases of middle and older ages, including epithelial cancers. In sub-Saharan Africa, where HIV prevalence approaches 20%, breast cancer has become the most common malignancy and cause of cancer-related death among women. Few studies have addressed the effects of HIV infection and ART on the clinical presentation, treatment, and prognosis of breast cancer. We propose to continue our study of those effects among South African women. In our prior work, we investigated demographic and clinical characteristics of 1200 breast cancer patients (18% HIV+), diagnosed 2007-2012 at the Chris Hani Baragwanath Academic Hospital Breast Clinic in Soweto, Johannesburg. Since 2015, for our R01-funded (CA192627) South African Breast Cancer and HIV Outcomes (SABCHO) study, we recruited and followed women with breast cancer newly diagnosed at 5 hospital centers in Johannesburg and KwaZulu Natal, to investigate the effects of HIV and ART on breast cancer treatment and outcomes. This collaboration of University of the Witwatersrand (Wits) and Columbia University Medical Center (CUMC) has yielded 16 publications to date (Wits contact PI and PD are former CUMC D43 trainees). We now propose: 1) to analyze determinants of mortality among the >3,000 women enrolled in the SABCHO study (21% HIV+), of whom 28.5% of HIV+ and 20.8% of HIV- patients have already died. We will assess cancer treatments, comorbidities, viral load control, clinical and sociodemographic mediators of the effects of HIV on mortality; 2) to examine the associations between sarcopenia , chemotherapy dose reductions and grade 3/4 toxicities, and early mortality among 600 black women (150 HIV+, 450 HIV-) newly diagnosed with BC; 3) to compare in HIV+ and HIV- patients, self-reported tamoxifen adherence and tolerance, plasma levels of tamoxifen and its metabolites, and factors that may affect these levels: treatment adherence, enzyme inhibition- and induction-based drug interactions, and genetic polymorphisms in enzymes involved in tamoxifen metabolism and pharmacokinetics; and 4) to train a) Sefako Makgatho University investigators in epidemiologic research, research ethics, contracts, grant budgeting and management, informed consent, survey research, and blood specimen logistical management; and b) masters students from Zimbabwe in pharmacogenomics and drug-drug interactions pertinent to breast cancer patients receiving ART and other chronic comorbidity treatments.

摘要：南方地区感染/未感染艾滋病毒的乳腺癌患者生存的新预测因素非洲随着抗逆转录病毒疗法 (ART) 提高 HIV 感染者的生存率，他们变得易感中老年疾病，包括上皮癌。在撒哈拉以南非洲地区，艾滋病毒乳腺癌患病率接近20%，已成为最常见的恶性肿瘤和发病原因女性癌症相关死亡。很少有研究探讨艾滋病毒感染和抗逆转录病毒治疗对乳腺癌的临床表现、治疗和预后。我们建议继续研究这些对南非妇女的影响。在我们之前的工作中，我们调查了人口统计和临床 2007 年至 2012 年在 Chris Hani 诊断的 1200 名乳腺癌患者（18% HIV+）的特征约翰内斯堡索韦托的巴拉瓦纳特学术医院乳腺诊所。自2015年以来，我们的R01资助 (CA192627) 南非乳腺癌和艾滋病毒结果 (SABCHO) 研究，我们招募并跟踪在约翰内斯堡和夸祖鲁纳塔尔省的 5 个医院中心新诊断出乳腺癌的妇女，研究艾滋病毒和抗逆转录病毒治疗对乳腺癌治疗和结果的影响。此次合作的金山大学 (Wits) 和哥伦比亚大学医学中心 (CUMC) 已取得 16 项成果迄今为止的出版物（Wits 联系人 PI 和 PD 是前 CUMC D43 学员）。我们现在建议：1）分析参与 SABCHO 研究的超过 3,000 名女性（21% HIV+）的死亡率决定因素，其中其中 28.5% 的 HIV+ 患者和 20.8% 的 HIV-患者已经死亡。我们将评估癌症治疗，合并症、病毒载量控制、艾滋病毒对死亡率影响的临床和社会人口学中介因素； 2) 检查肌肉减少症、化疗剂量减少和 3/4 级毒性之间的关联， 600 名新诊断患有 BC 的黑人女性（150 名 HIV+，450 名 HIV-）的早期死亡； 3) 比较 HIV+ 和 HIV- 患者自我报告的他莫昔芬依从性和耐受性、血浆水平他莫昔芬及其代谢物，以及可能影响这些水平的因素：治疗依从性、酶基于抑制和诱导的药物相互作用，以及参与酶的遗传多态性他莫昔芬代谢和药代动力学；和 4) 培训 a) Sefako Makgatho 大学流行病学研究、研究伦理、合同、拨款预算和管理、知情同意、调查研究和血液样本后勤管理; b) 来自津巴布韦的药物基因组学和药物相互作用硕士生与接受 ART 和其他慢性合并症治疗的乳腺癌患者相关。