Long-Term Trends in Breast Cancer Tumor Profiles & Disparities

描述（由申请人提供）：我们提出的探索性研究集中在一个重要的问题上：缺乏乳腺癌肿瘤概况的长期趋势数据，总体上，与种族/民族和社会经济地位有关。这些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是可以改变的。相关的例子包括：(1)在2002年妇女健康倡议结果公布后，随着激素治疗使用的急剧减少，乳腺癌发病率的长期上升和最近下降，美国的下降因雌激素受体（ER）状况、社会经济地位和种族/民族而异；(2)我们的新研究记录了1992年至2005年间，美国乳腺癌病例中ER+肿瘤的白人/黑人比值比也同样上升和下降。这些发现，以及对乳腺癌进化和生物标志物的表观遗传调控的新研究表明：(a)乳腺癌的生物学表达和社会模式远不是固定的，而是可以改变的；(b)分析长期趋势的数据对于理解和减少乳腺癌发病率、生存率和死亡率的种族/民族和社会经济差异的原因具有重要意义。在本R21中，我们建议评估对乳腺癌肿瘤概况的长期趋势进行R01的可行性，包括总体、种族/民族和社会经济地位，通过确定：(1)当前的生物标志物检测是否可以用于可追溯到20世纪40年代的肿瘤标本，以及(2)在选定的研究人群中，我们可以定位肿瘤块和医疗图表的病例比例是否足以实现预期的R01。乳腺肿瘤标本的来源将是美国（US）和新西兰（NZ），这两个国家拥有独特的长期癌症登记数据，并且在乳腺癌发病率、生存率和死亡率方面有充分记录的种族/民族和社会经济差异。因此，我们的具体目标是：目标1：确定查找20世纪40年代至2010年乳腺癌患者肿瘤标本和医疗图表的可行性，从：(a) Kaiser Permanente （KP）研究部（加利福尼亚州奥克兰），其肿瘤记录和患者数据库可追溯到1947年，以及(b)新西兰癌症登记处，成立于1948年；目的2：确定目前的乳腺癌生物标志物检测方法是否可以有效地用于可追溯到20世纪40年代的标本，这些标本来自Kaiser Permanente (1947-2010)；目标3：确定目标1和2的结果是否支持开发R01来研究乳腺癌肿瘤概况中种族/民族和社会经济差异患病率的长期趋势的可行性（使用KP和NZ数据）；目标4：通过发表科学手稿传播结果，如果有必要，使用结果准备R01，对乳腺癌肿瘤特征趋势以及这些生物标志物的种族/民族和社会经济差异进行首次长期和跨国（美国和新西兰）分析，对预防和治疗具有重要意义。

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.