Analysis of Late Recurrence in Breast Cancer

描述(申请人提供)：与大多数癌症不同，乳腺癌 可在最初诊断数年后复发。休眠的机制，或 肿瘤潜伏期，都是未知的。我们发现许多乳腺癌表现出一种 当转移到淋巴时，它们的增殖率显著降低 节点。我们假设结节转移可能以静止肿瘤的形式存活。 对化疗有抵抗力并能够产卵的沉积物 原发灶切除后多年内复发。 一种解释可能是乳腺肿瘤依赖于肿瘤的存在 生长因子存在于乳房内，但不存在于淋巴结中。晚些 复发可能代表生长因子独立性和/或 迁移到新的富含生长因子的区域(例如肝脏或骨髓)。我们的 一项旨在确定扩散速度和增长因素的作用的提案 在乳腺癌不同寻常的自然病史中，两者都是预后因素 并作为潜在的治疗靶点。在AIM I中，我们将开发大型(&gt；300 患者)队列中的乳腺癌患者，并使用新的 发展了组织微阵列技术。这些队列将包括匹配的 原发灶和转移灶的组织集。我们会 检测增殖率及其与生长因子表达的相关性 和生长因子受体的激活。在AIM II中，我们将使用新鲜的 分离组织以确定原发肿瘤中存在的生长因子的量 和结节转移。Aim III将分析原始人的反应 乳腺肿瘤对外源性生长因子的促进作用，集中于两者的增殖 以及其他肿瘤激活的下游标志物。结果来自所有人 AIMS将与患者存活率和复发率相关。 这项研究的主要研究员是罗伯特·L·坎普，医学博士，他 最近完成了他在耶鲁纽黑文医院的病理学实习。 坎普博士对从事翻译研究很感兴趣， 专注于更好的癌症诊断和开发工具 以确定针对个别肿瘤的适当治疗方法的技术。 这项提议的导师是David Rimm，医学博士，博士，他是一位成熟的 耶鲁大学病理学系研究员兼细胞病理学家 大学。Rimm博士在基础和基础两个领域都有成熟的职业生涯 翻译研究。拟议的研究地点，教育部 病理学，有智力和体力资源来支持博士。 Camp的研究，包含了顶尖的调查人员和 最先进的“核心设施。

DESCRIPTION (provided by applicant): Unlike most carcinomas, breast cancer can recur years after its initial diagnosis. The mechanisms of dormancy, or tumor latency, are unknown. We have found that many breast cancers exhibit a marked reduction in their proliferation rate when they metastasize to lymph nodes. We hypothesize that nodal metastases may survive as quiescent tumor deposits, which are resistant to chemotherapy, and capable of spawning aggressive recurrences many years after the resection of the primary lesion. One explanation may be that breast tumors are dependent on the presence of growth factors found within the breast but absent in lymph nodes. Late recurrences may represent the development of growth factor independence and/or migration to new growth factor rich areas (e.g., liver or bone marrow). Our proposal seeks to determine the role of proliferation rates and growth factors in the unusual natural history of breast cancer, both as prognostic factors and as potential therapeutic targets. In Aim I, we will develop large (>300 patients) cohorts of breast cancer patients and analyze them using a newly developed tissue microarray technique. These cohorts will include matched sets of tissue from both primary lesions and nodal metastases. We will examine proliferation rates and correlate them with growth factor expression and growth factor receptor activation. In Aim II, we will use freshly isolated tissue to determine the amount of growth factor present in primary and nodal metastases. Aim III will analyze the responses of primary human breast tumors to exogenous growth factors, concentrating both on proliferation as well as other downstream markers of tumor activation. Results from all aims will be correlated with patient survival and recurrence rates. The principal investigator in this study is Robert L. Camp, M.D., Ph.D., who has recently completed his residency in pathology at Yale New Haven Hospital. Dr. Camp is interested in pursuing a career in translational research, concentrating on better tools for the diagnosis of cancer and the development of techniques to determine the appropriate treatment for individual tumors. The mentor for this proposal is David Rimm, M.D., Ph.D., who is an established researcher and cytopathologist in the Department of Pathology at Yale U n iversity. Dr. Rimm has an established career in both basic and translational research. The proposed research site, the Department of Pathology, has both the intellectual and physical resources to support Dr. Camp's research, and contains both top quality investigators and "state-of- the-art" core facilities.