c-erbB-2 and Risk of Contralateral Breast Cancer

描述(由应聘者提供)：应聘者最近接受了弗雷德·哈钦森癌症研究中心流行病学的初级教员职位。他的直接目标是追求自己对乳腺癌病因学的兴趣，并进一步发展他的研究技能和经验。他的长期目标是建立一个职业生涯，促进癌症流行病学和预防方面的科学知识。拟议的研究职业发展计划包括遗传和分子流行病学、研究病理学和生物统计学方面的高级培训。候选人还将发展他的助学金写作技能，并在拟议的获奖期内提交R03和R01助学金。提出了两个流行病学研究项目，涉及使用生物标记物，扩展了候选人和他的导师进行的对侧乳腺癌(CBC)的初步工作。CBC的最大风险因素是女性首次确诊乳腺癌的年龄，因为在45岁之前确诊的女性患CBC的风险是从未被诊断为乳腺癌的女性患首次乳腺癌风险的5.4倍。然而，关于哪些因素使年轻的乳腺癌患者容易患上CBC，我们知之甚少。我们的试点数据表明，在45岁之前被诊断为首次乳腺癌的女性中，45%的c-erbB-2阳性肿瘤患者患CBC的风险是后者的1.7倍(95%可信区间：1.0-3.0)。通过两项研究，一项是对1996-2007年间21-49岁确诊为首次乳腺癌的妇女进行嵌套病例对照研究，另一项是对1,285名妇女进行队列研究，这些妇女在1983-1992年间被诊断为21-45岁的首次乳腺癌，并在2001年被跟踪诊断为CBC，我们将评估c-erbB-2在CBC病因学中的作用。需要检验的具体假设是：1)在年轻女性确诊的首发乳腺癌中c-erbB-2的表达是否增加了CBC的风险？2)c-erbB-2在首发乳腺癌中的表达是否预示着其在CBCs中的表达？3)患者、肿瘤或治疗因素是否影响CBC中c-erbB-2和其他肿瘤标志物的表达？5)首发肿瘤中表达的其他肿瘤标志物与其在CBCs中的表达有何关系？如果我们证实c-erbB-2可以预测CBC的发现，这将支持我们的假设，即c-erbB-2在CBC的病因中起着重要作用，并表明c-erbB-2阳性肿瘤的妇女应该密切监测CBC。

DESCRIPTION (provided by applicant): The candidate has recently accepted a junior faculty member position in epidemiology at the Fred Hutchinson Cancer Research Center. His immediate goals are to pursue his interests in breast cancer etiology, and to further his research skills and experience. His long term goal is to establish a career that will advance scientific knowledge concerning cancer epidemiology and prevention. The proposed research career development plan involves advanced training in genetic and molecular epidemiology, research pathology, and biostatistics. The candidate will also develop his grant writing skills and submit both R03 and R01 grants during the proposed award period. Two epidemiologic research projects involving the use of biomarkers that expand on preliminary work on contralateral breast cancer (CBC) conducted by the candidate and his mentor are proposed. The strongest risk factor for CBC is age at diagnosis of a woman's first primary breast cancer, as women diagnosed before age 45 have a 5.4-fold greater risk of CBC compared to the risk women never diagnosed with breast cancer have of developing a first breast cancer. However, little is known about what factors predispose young breast cancer patients to develop CBC. Our pilot data suggest that among women diagnosed with a first breast cancer before age 45 years, the 45% of subjects with a c-erbB-2 positive tumor have a 1.7-fold (95% confidence interval: 1.0-3.0) excess risk of CBC. Through two studies, a nested case-control study of women diagnosed with a first breast cancer from 1996-2007 at age 21-49 years, and a cohort study of 1,285 women, diagnosed with a first breast cancer at 21-45 years of age from 1983-1992 and followed through 2001 for the diagnosis of CBC, we will evaluate the role that c-erbB-2 plays in CBC etiology. The specific hypotheses to be tested are: 1) Does c-erbB-2 expression in first breast cancers diagnosed in young women increase their CBC risk? 2) Is c-erbB-2 expression in first breast cancers predictive of its expression in CBCs? 3) Are there patient, tumor, or treatment factors that influence the expression of c-erbB-2 and other tumor markers in CBCs? 5) How do other tumor markers expressed by first tumors correlate to their expression in CBCs? If we confirm our finding that c-erbB-2 is predictive of CBC, this would support our hypothesis that c-erbB-2 plays an important role in the etiology of CBC and indicate that women with c-erbB-2 positive tumors should be closely monitored for CBC.