Epidemiology of the four most frequent cancers following breast cancer

描述(申请人提供)：浸润性乳腺癌后的五年存活率目前为90%，估计有297万美国妇女是乳腺癌幸存者。浸润性乳腺癌的高发病率，每年有超过22万名美国妇女新确诊，加上存活率的持续提高，导致越来越多的妇女面临发展为第二原发癌的风险。事实上，在美国女性中确诊的所有第二原发癌中，有41%发生在乳腺癌幸存者中。大约10%的乳腺癌幸存者会发展成第二种原发癌症。第二原发癌最常见的四个部位，乳腺癌、肺癌、结肠癌和子宫内膜，占第二原发癌的70%。乳腺癌幸存者罹患第二原发癌的明显风险是有充分证据的，但对这些第二原发癌的病因学和分子决定因素知之甚少，由于这一证据差距，很少或根本没有关于第二原发癌风险的信息被纳入预防工作和临床护理。还没有研究全面而同时地调查在乳腺癌幸存者中诊断出的四种主要第二原发癌的病因。剖析这些第二种癌症的治疗和风险之间的关系，澄清患者/临床因素的贡献，包括可改变的暴露，并对第一原发癌进行分子图谱分析，以区分哪些是第二原发癌风险最高和最低的，这可能会使风险分层、量身定做的监测、治疗选择、预防干预等方面取得进展。 以及对生物机制的理解。为了弥补这一差距，我们提出了一项以人群为基础的病例队列研究，由2600名乳腺癌幸存者组成，重点研究首次诊断为浸润性乳腺癌后确诊的四种最常见的第二原发癌的流行病学、临床和分子决定因素。比较已患第二原发癌和未患第二原发癌的妇女，我们的主要具体目标如下：1.评估流行病学/医学因素(包括生活方式因素；常见疾病的药物使用；癌症家族史)与随后发生乳腺癌、肺癌、结肠癌和子宫内膜癌的风险之间的关系。2.评估首次原发乳腺癌的治疗与随后的乳腺癌、肺癌、结肠癌和子宫内膜癌风险之间的关系。3.评估常规收集的第一原发癌的临床肿瘤特征(组织学、肿瘤大小、淋巴结状态、分级、ER状态、 PR状态和HER2状态)和随后的乳腺癌、肺癌、结肠癌和子宫内膜癌的风险。4.利用全基因组基因表达平台，发现并初步验证与乳腺癌、肺癌、结肠癌和子宫内膜癌风险相关的新的肿瘤生物标志物。

DESCRIPTION (provided by applicant): Five-year survival after invasive breast cancer is now at 90% and an estimated 2.97 million U.S. women are breast cancer survivors. The high incidence of invasive breast cancer, with over 220,000 U.S. women newly diagnosed every year, coupled with continued advances in survival has resulted in an ever- increasing number of women at risk of developing a second primary cancer. Indeed, 41% of all second primary cancers diagnosed among U.S. women occur among breast cancer survivors. Approximately 10% of breast cancer survivors will develop a second primary cancer. The four most common sites of second primary cancer, breast, lung, colon and endometrium, account for 70% of these second primaries. The appreciable risk of second primary cancer in breast cancer survivors is well-documented, yet relatively little is known about the etiologic and molecular determinants of these second primaries and little to no information on second primary cancer risk has been incorporated into preventive efforts and clinical care because of this evidence gap. No studies have comprehensively and simultaneously investigated the etiology of the four major second primary cancers diagnosed in breast cancer survivors. Dissecting relationships between therapies and risk of these second cancers, clarifying contributions of patient/clinical factors including modifiable exposures, and molecular profiling first primary breast tumors so as to distinguish those at highest and lowest risk of second primaries would potentially allow advances in risk stratification, tailored surveillance, treatment choice, preventive interventions, and understanding of biologic mechanisms. To address this gap we propose a population-based case-cohort study consisting of 2 600 breast cancer survivors focused on epidemiologic, clinical and molecular determinants of the four most common second primary cancers diagnosed after a first diagnosis of invasive breast cancer. Comparing women who have and have not developed second primary cancers, our primary specific aims are as follows: 1. To assess associations between epidemiologic/medical factors (including lifestyle factors; medications use for common medical conditions; family history of cancer) and risk of subsequent primary cancer of the breast, lung, colon and endometrium. 2. To assess associations between treatments for first primary breast cancer and risk of subsequent primary cancer of the breast, lung, colon and endometrium. 3. To assess associations between routinely collected clinical tumor characteristics of the first primary cancer (histology, tumor size, nodal status, grade, ER status, PR status, and HER2 status) and risk of subsequent primary cancer of the breast, lung, colon and endometrium. 4. To discover and preliminarily validate novel tumor biomarkers associated with risk of subsequent primary cancer of the breast, lung, colon and endometrium using a genome-wide gene expression platform.