Long-Term Trends in Breast Cancer Tumor Profiles & Disparities

乳腺癌肿瘤概况的长期趋势

• 批准号: 8636410
• 负责人: NANCY KRIEGER
• 金额: $ 17.29万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8636410
• 关键词: Address; Age; Antigens; Back; Biological; Biological Assay; Biological Markers; Biological Preservation; Breast Cancer Prevention; Cancer Patient; Chemicals; Computers; Country; Cytokeratin; Cytokeratin-8 Staining Method; Data; Data Analyses; Databases; Diagnosis; Ensure; Epidermal Growth Factor Receptor; Epigenetic Process; Estrogen Receptor Status; Estrogen Receptors; Ethnic Origin; Evolution; Gene Expression Profiling; Hospitals; Human; Incidence; Investigation; Knowledge; Longitudinal Studies; Mammary Neoplasms; Manuscripts; Measures; Medical; Methods; Molecular; National Cancer Institute; New Zealand; Odds Ratio; Patients; Pattern; Population Study; Prevalence; Prevention; Preventive Intervention; Progesterone Receptors; Public Hospitals; Publications; Publishing; Race; Records; Regulation; Research; Rosa; Sampling; Socioeconomic Status; Source; Specimen; Testing; Time; Tissue Microarray; Tumor Biology; United States; United States National Institutes of Health; Vimentin; Woman; Women' s Health; Work; base; behavioral/social science; cancer health disparity; cancer therapy; design; falls; health disparity; hormone therapy; malignant breast neoplasm; mortality; neoplasm registry; public health relevance; racial and ethnic; racial and ethnic disparities; social; social science research; socioeconomics; trend; tumor

DESCRIPTION (provided by applicant): Our proposed exploratory study focuses on a significant problem: the absence of data on long-term trends in breast cancer tumor profiles, overall and in relation to race/ethnicity and socioeconomic position. The value of such long-term data is that they can uniquely reveal what aspects of tumor biology are amenable to change. Relevant examples include: (1) the long-term rise and recent fall of breast cancer incidence, following sharp decreases of hormone therapy use after publication of the Women's Health Initiative results in 2002, with US declines varying by estrogen receptor (ER) status, socioeconomic position and race/ethnicity, and (2) our new study documenting that between 1992 and 2005, the US white/black odds ratio for ER+ tumors among breast cancer cases likewise rose and fell. These findings, along with new work on the epigenetic regulation of breast tumor evolution and biomarkers, suggest 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. In this R21, we accordingly propose to assess the feasibility of conducting an R01 on long-term trends in breast cancer tumor profiles, overall and by race/ethnicity and socioeconomic position, by determining: (1) if current biomarker assays can be used on tumor specimens extending back to the 1940s, and (2) if, in the selected study population, the proportion of cases for whom we can locate both tumor blocks and medical charts is sufficient for the envisioned R01. The source of the breast tumor specimens will be the United States (US) and New Zealand (NZ), two countries with uniquely long-term cancer registry data and well- documented racial/ethnic and socioeconomic disparities in breast cancer incidence, survival, and mortality. Our Specific Aims accordingly are: Aim 1: Determine the feasibility of locating breast cancer patients' tumor specimens and medical charts, spanning from the 1940s to 2010, from: (a) Kaiser Permanente (KP) Division of Research (Oakland, CA), whose tumor records and patient database extends back to 1947, and (b) The New Zealand Cancer Registry, established in 1948; Aim 2: Determine whether current assays for breast cancer biomarkers can validly be employed with specimens dating back to the 1940s, as obtained from Kaiser Permanente (1947-2010); Aim 3: Determine if results for Aims 1 and 2 support the feasibility of developing an R01 to study long-term trends in prevalence of - and racial/ethnic and socio- economic disparities in - breast cancer tumor profiles (using the KP and NZ data); and Aim 4: Disseminate results by publishing scientific manuscripts and, if warranted, 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（由申请人提供）：我们提出的探索性研究重点是一个重大问题：缺少有关乳腺癌肿瘤概况的长期趋势的数据，整体以及与种族/种族和社会经济地位有关。这种长期数据的价值在于，它们可以独特地揭示肿瘤生物学的哪些方面可以改变。 Relevant examples include: (1) the long-term rise and recent fall of breast cancer incidence, following sharp decreases of hormone therapy use after publication of the Women's Health Initiative results in 2002, with US declines varying by estrogen receptor (ER) status, socioeconomic position and race/ethnicity, and (2) our new study documenting that between 1992 and 2005, the US white/black odds ratio for ER+ tumors among breast cancer cases likewise玫瑰倒下。这些发现，以及有关乳腺肿瘤进化和生物标志物的表观遗传调节的新工作，表明：（a）乳腺癌的生物表达和社会形态，远非固定，可以改变，并且（b）对长期趋势进行分析具有重要的意义，使人们对理解种族/种族/种族/种族和社会经济性疾病的疾病和越来越多的疾病，并在乳腺癌中降低了乳腺癌的疾病，并保持了乳腺癌的疾病，并保持了癌症，并保持了癌症的疾病。 在此R21中，我们因此提议评估R01对乳腺癌肿瘤谱的长期趋势的可行性，整体和种族/族裔和社会经济位置，通过确定：（1）当前的生物标志物测定可以使用当前的生物标志物在肿瘤的肿瘤标本中使用，并在1940年代进行的肿瘤中使用该肿瘤，以及（2），如果该肿瘤的范围是（2），那么（2）的肿瘤（2），我们的肿瘤范围（2），我们的肿瘤可能会在所选的anmor中，以及（2），我们的肿瘤可能会在所选的范围内（我们的肿瘤范围）进行了分配，那么我们的肿瘤标本可以使用。对于设想的R01，图表就足够了。乳腺肿瘤标本的来源将是美国（美国）和新西兰（NZ），这是两个具有独特的长期癌症注册表数据的国家，以及据此记录的种族/种族和社会经济差异，在乳腺癌发病率，生存和死亡率中。 Our Specific Aims accordingly are: Aim 1: Determine the feasibility of locating breast cancer patients' tumor specimens and medical charts, spanning from the 1940s to 2010, from: (a) Kaiser Permanente (KP) Division of Research (Oakland, CA), whose tumor records and patient database extends back to 1947, and (b) The New Zealand Cancer Registry, established in 1948; AIM 2：确定当前的乳腺癌生物标志物的测定是否可以通过可追溯到1940年代的标本有效地使用，如Kaiser Permanente（1947-2010）所获得的那样；目标3：确定目标1和2的结果是否支持开发R01来研究 - 乳腺癌肿瘤谱的长期趋势的可行性，以及种族/种族和社会经济差异（使用KP和NZ数据）；目标4：通过发表科学手稿来传播结果，如果有必要，则使用结果来准备R01，以对乳腺癌肿瘤特征以及这些生物标志物中的种族/族裔和社会经济差异的趋势进行第一长期和越野（US和NZ）分析，对这些生物标志物进行了主要影响，并对预防和治疗产生了重大影响。

项目成果

Analyzing historical trends in breast cancer biomarker expression: a feasibility study (1947-2009).

• DOI: 10.1038/npjbcancer.2015.16
• 发表时间: 2015
• 期刊: NPJ breast cancer
• 影响因子: 5.9
• 作者: Krieger N;Habel LA;Waterman PD;Shabani M;Ellison-Loschmann L;Achacoso NS;Acton L;Schnitt SJ
• 通讯作者: Schnitt SJ