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

• 批准号: 9982617
• 负责人: Herbert Cubasch
• 金额: $ 35万
• 依托单位: WITS HEALTH CONSORTIUM (PTY), LTD
• 依托单位国家: 美国
• 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/9982617
• 关键词: Academic Medical Centers; Achievement; Address; Adherence; Affect; Africa South of the Sahara; African; 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; Communities; Contracts; Data; Development; Diagnosis; Disadvantaged; 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 antiretroviral; HIV diagnosis; HIV therapy; Hospitals; Incidence; Individual; Informed Consent; Life Expectancy; Link; Liver; Logistics; Malignant Neoplasms; Mediator of activation protein; 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; Preparation; Prevalence; 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; Treatment outcome; Universities; Viral Load result; Woman; Work; Zimbabwe; adjuvant endocrine therapy; antiretroviral therapy; base; 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; improved; insight; lectures; low and middle-income countries; malignant breast neoplasm; mortality; novel; outcome forecast; premature; recruit; sarcopenia; sociodemographics; survival prediction; therapy adherence; treatment adherence

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：南方患有/患有HIV的乳腺癌患者生存的新预测指标 非洲 随着抗逆转录病毒疗法（ART）提高了艾滋病毒感染者的生存率，它们变得易感性 到包括上皮癌在内的中年和老年疾病。在撒哈拉以南非洲，艾滋病毒的地方 患病率接近20％，乳腺癌已成为最常见的恶性肿瘤和原因 女性与癌症有关的死亡。很少有研究解决了艾滋病毒感染和艺术对 乳腺癌的临床表现，治疗和预后。我们建议继续研究 南非妇女的影响。在先前的工作中，我们调查了人口统计和临床 Chris Hani的1200名乳腺癌患者的特征（18％HIV+）被诊断为2007-2012 约翰内斯堡索韦托的Baragwanath学术医院乳房诊所。自2015年以来，我们的R01资助 （CA192627）南非乳腺癌和HIV结局（SABCHO）研究，我们招募并遵循 乳腺癌的妇女在约翰内斯堡和夸祖鲁·纳塔尔的5个医院中心新诊断为 研究艾滋病毒和艺术对乳腺癌治疗和结局的影响。这种合作 威特沃特斯兰大学（WITS）和哥伦比亚大学医学中心（CUMC）产生了16 迄今为止的出版物（WITS联系PI和PD是前CUMC D43受训者）。我们现在建议：1） 分析> 3,000名参加SABCHO研究（21％HIV+）的妇女中死亡率的决定因素， 艾滋病毒+的28.5％和20.8％的艾滋病毒患者已经死亡。我们将评估癌症治疗， HIV对死亡率的影响的合并症，病毒负荷控制，临床和社会人口统计学介体； 2）检查肌肉减少症，化学疗法降低和3/4毒性之间的关联， 600名黑人妇女（150 HIV+，450 HIV-）的早期死亡率是新诊断为BC的； 3）比较HIV+和HIV患者，自我报告的他莫昔芬的依从性和耐受性，血浆水平的水平 他莫昔芬及其代谢产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大学在流行病学研究，研究伦理，合同， 授予预算和管理，知情同意，调查研究和血液标本后勤 管理; b）津巴布韦的硕士学生在药物基因组学和药物互动中 与接受ART和其他慢性合并症治疗的乳腺癌患者有关。