Long-term trends in breast cancer DNA copy number alterations & disparities

乳腺癌 DNA 拷贝数改变的长期趋势

• 批准号: 9271922
• 负责人: NANCY KRIEGER
• 金额: $ 8.53万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-12 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9271922
• 关键词: Address; Age; Back; Biological; Biological Assay; Biological Markers; Breast Cancer Patient; California; Characteristics; Chemicals; Classification; Complement; Country; Cytokeratin; DNA; DNA copy number; Data; Data Analyses; Databases; Ensure; Epidermal Growth Factor Receptor; Estrogen Receptors; Ethnic Origin; Formalin; Funding; Grant; Health Priorities; Human; Immune; Incidence; Investigation; Knowledge; Link; Longitudinal Studies; Longitudinal trends; Mammary Neoplasms; Manuscripts; Medical; Methods; Morphology; National Cancer Institute; New Zealand; Odds Ratio; Paraffin Embedding; Patients; Pattern; Pilot Projects; Population; Prevalence; Prevention; Preventive Intervention; Process; Progesterone Receptors; Public Hospitals; Publications; Publishing; Race; Records; Research; Rosa; Sampling; Socioeconomic Status; Specimen; Testing; Time; Tissue Microarray; Tumor Biology; Tumor Markers; United States; Woman; Women' s Health; Work; base; breast cancer diagnosis; cancer epidemiology; cancer health disparity; complement C2a; design; health disparity; hormone therapy; immunohistochemical markers; innovation; malignant breast neoplasm; molecular phenotype; mortality; neoplasm registry; public health relevance; racial and ethnic disparities; response; secondary analysis; social; social disparities; socioeconomic disparity; socioeconomics; trend; trend analysis; tumor

 DESCRIPTION (provided by applicant): In this R03, we propose to add new assays for DNA copy number alteration, to allow us to test for feasibility and reliability of using these assays o older breast tumor specimens, dating back to the 1950s. These new assays and new analysis will innovatively and significantly build on our funded R21 (5 R21 CA166115-02), which is focusing on ascertaining the feasibility of obtaining breast cancer tumor specimens dating back to the 1950s, to allow for research on trends in both tumor characteristics and social disparities in these characteristics. The significant problem our R21 addresses is: the absence of data on long-term trends in breast cancer tumor profiles, overall and by race/ethnicity and socioeconomic position. As articulated in the original application, such long-term data can uniquely reveal what aspects of tumor biology are amenable to change. Relevant examples include our recent study documenting that between 1992 and 2005, the US white/black odds ratio for ER+ tumors among breast cancer cases likewise rose and fell, likely linked to changes in hormone therapy use after publication of the Women's Health Initiative results in 2002. Key implications are that: (a) the biological expression and social patterning of breast cancer, far from being fixed, can change, and (b) analyzing data on long-term trends has important implications for both understanding the causes of and reducing racial/ethnic and socioeconomic disparities in breast cancer incidence, survival, and mortality. Our newly proposed Aim 2d has two parts: Aim 2d1: extract DNA from the 30 tumor blocks obtained for Aim 1 (5 specimens per decade, from 1947-1959 to 2000-2009, randomly selected from invasive cases of breast cancer diagnosed among women age 50-64, obtained from the Kaiser Permanent (KP) Division of Research in Northern California); Aim 2d2: determine whether current assays for DNA copy number alteration can validly be employed with the study specimens. The new assays complement those for Aims 2a-c, for which preliminary results indicate all specimens displayed excellent histo-morphology and both appropriate values and excellent test-retest reliability for key immune-histo-chemical markers: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR), and Ki67, allowing for classification of molecular phenotypes. Results will inform the R21's Aim 3: Determine if results for Aims 2 support the feasibility of developing an R01 to study long-term trends in prevalence of - and racial/ethnic and socioeconomic disparities in - breast cancer tumor profiles (using the KP & NZ data), and Aim 4: use results to prepare an R01 to conduct the first long- term and cross-country (US and NZ) analysis of trends in breast cancer tumor profiles and racial/ethnic and socioeconomic disparities in these biomarkers, with major implications for prevention and treatment.

 描述（由适用提供）：在此R03中，我们建议添加用于DNA拷贝数更改的新测定法，以使我们能够测试使用这些测定的可行性和可靠性，以期可以追溯到1950年代。这些新的测定和新分析将在我们资助的R21（5 R21 CA166115-02）上进行创新和显着建立，该R21（5 R21 CA166115-02）着重于确定可以追溯到1950年代获得乳腺癌肿瘤标本的可行性，以允许在这些特征的肿瘤特征和社会偏见中研究这些特征的趋势。我们的R21解决的重大问题是：缺少有关乳腺癌肿瘤概况的长期趋势的数据，整体以及种族/种族和社会经济地位。正如原始应用中所阐明的那样，这样的长期数据可以独特地揭示肿瘤生物学的哪些方面可以改变。相关示例包括我们最近的研究文档，即1992年至2005年之间，乳腺癌病例中的ER+肿瘤的美国白人/黑色优势比同样上升和下降，这可能与妇女疗法在2002年发表妇女健康倡议后的使用变化有关。乳腺癌发病率，生存和死亡率中种族/种族和社会经济差异的原因和减少原因。我们新提出的AIM 2D有两个部分：AIM 2D1：从AIM 1获得的30个肿瘤块中提取DNA（从1947- 1959年到2009年，每十年的5个标本，每十年至2000年至2009年，从50-64岁的妇女中诊断出的乳腺癌诊断为50-64岁的乳腺癌，从Kaiser永久（KP）北加州北加州的Kaiser Permanent（KP）分校获得）; AIM 2D2：确定是否可以在研究标本中有效使用DNA拷贝数改变的当前测定法。新测定完成了目标2A-C的完成，初步结果表明所有标本都表现出了出色的组织形态学和适当的值和适当的测试可靠性，并且对关键免疫 - 含量化学标志物的良好测试可靠性：雌激素受体（ER）：孕酮受体（PR），人类表皮生长因子2（Her2），Cytrer 2（Her2），cytoser（Cytoser）（Ckk）（Ckk）5/ （EGFR）和KI67，允许分子表型分类。结果将告知R21的目标3：确定目标2是否支持开发R01以研究长期趋势的可行性 - 以及种族/族裔和种族和社会经济差异 - 乳腺癌肿瘤概况 - 使用KP和NZ数据（使用KP＆NZ数据）（使用KP和NZ数据），并使用R01进行R01进行趋势和NZ的趋势（US和NZ），并使用R01进行趋势（US和NZ）。这些生物标志物中的种族/种族和社会经济差异，对预防和治疗产生了重大影响。