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。 他的近期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，将推进有关癌症流行病学和预防的科学知识。 拟议的研究职业发展计划涉及遗传和分子流行病学，研究病理学和生物统计学的高级培训。 候选人还将发展他的赠款写作技巧，并在拟议的奖励期间提交R03和R01赠款。 两个流行病学研究项目，涉及使用生物标志物，扩大对侧乳腺癌（CBC）的候选人和他的导师进行的初步工作提出。 CBC最强的风险因素是女性首次原发性乳腺癌诊断时的年龄，因为45岁之前诊断的女性患CBC的风险是从未诊断出乳腺癌的女性患首次乳腺癌的风险的5.4倍。 然而，人们对年轻乳腺癌患者易患CBC的因素知之甚少。 我们的试验数据表明，在45岁之前诊断出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，一项是对1996 - 2007年21 - 49岁诊断为首次乳腺癌的女性进行的巢式病例对照研究，另一项是对1,285名女性进行的队列研究，这些女性在1983 - 1992年21 - 45岁诊断为首次乳腺癌，并随访至2001年，以诊断CBC，我们将评估c-erbB-2在CBC病因学中的作用。 具体的假设是：1）c-erbB-2表达在第一次乳腺癌诊断的年轻妇女增加其CBC的风险？ 2)c-erbB-2在首次乳腺癌中的表达能否预测其在CBCs中的表达？ 3)是否有患者、肿瘤或治疗因素影响c-erbB-2和其他肿瘤标志物在CBCs中的表达？ 5)第一肿瘤表达的其他肿瘤标志物如何与它们在CBC中的表达相关？ 如果我们证实c-erbB-2是CBC的预测因子，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c-erbB-2阳性肿瘤的妇女应密切监测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.