Epidemiology of the four most frequent cancers following breast cancer

描述（由申请人提供）：浸润性乳腺癌后的五年生存率目前为90%，估计有297万美国女性是乳腺癌幸存者。浸润性乳腺癌的高发病率，每年有超过22万的美国女性新诊断，再加上生存率的持续提高，导致越来越多的女性面临患第二原发性癌症的风险。事实上，在美国女性中诊断出的所有第二原发性癌症中，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为第二原发癌症。乳腺癌、肺癌、结肠癌和子宫内膜这四个最常见的第二原发癌部位占第二原发癌的70%。乳腺癌幸存者发生第二原发癌的明显风险是有据可查的，但对这些第二原发癌的病因学和分子决定因素所知相对较少，由于这一证据差距，关于第二原发癌风险的信息很少甚至没有被纳入预防工作和临床护理。目前还没有研究对乳腺癌幸存者中诊断出的四种主要第二原发癌症的病因进行全面和同步的调查。剖析治疗方法和这些第二种癌症风险之间的关系，阐明患者/临床因素的贡献，包括可改变的暴露，以及第一原发乳腺癌的分子谱，以区分第二原发风险最高和最低的乳腺癌，可能会在风险分层、量身定制的监测、治疗选择、预防性干预方面取得进展。

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.