c-erbB-2 and Risk of Contralateral Breast Cancer

描述（由申请人提供）：候选人最近接受了弗雷德哈钦森癌症研究中心流行病学初级教员的职位。他的直接目标是追求他对乳腺癌病因学的兴趣，并进一步提高他的研究技能和经验。他的长期目标是建立一个职业生涯，将推动有关癌症流行病学和预防的科学知识。提出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。候选人亦须发展其写作能力，并在计划资助期内提交R03及R01补助金。提出了两项涉及使用生物标志物的流行病学研究项目，这些项目扩展了候选人及其导师进行的对侧乳腺癌（CBC）的初步工作。CBC的最大危险因素是女性首次原发性乳腺癌的诊断年龄，因为45岁之前被诊断为CBC的女性患CBC的风险比从未被诊断为乳腺癌的女性患首次乳腺癌的风险高5.4倍。然而，对于年轻乳腺癌患者易患CBC的因素知之甚少。我们的试点数据显示，在45岁前诊断为首次乳腺癌的女性中，45%的c-erbB-2阳性肿瘤患者的CBC风险增加了1.7倍（95%置信区间：1.0-3.0）。通过两项研究，一项巢式病例对照研究，研究对象是1996-2007年21-49岁首次诊断为乳腺癌的女性，另一项队列研究，研究对象是1983-1992年21-45岁首次诊断为乳腺癌并随访至2001年诊断为CBC的1285名女性，我们将评估c-erbB-2在CBC病因学中的作用。需要验证的具体假设是：1)年轻女性首次诊断为乳腺癌的c-erbB-2表达是否会增加其CBC风险？2) c-erbB-2在首发乳腺癌中的表达能否预测其在CBCs中的表达？3)是否存在患者、肿瘤或治疗因素影响cbc中c-erbB-2和其他肿瘤标志物的表达？5)首发肿瘤表达的其他肿瘤标志物与它们在CBCs中的表达有何关联？如果我们证实c-erbB-2可以预测CBC，这将支持我们的假设，即c-erbB-2在CBC的病因学中起重要作用，并表明患有c-erbB-2阳性肿瘤的女性应密切监测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.