Analysis of Late Recurrence in Breast Cancer

描述（由申请人提供）：与大多数癌症不同，乳腺癌 可能在初次诊断后数年复发。 休眠机制，或 肿瘤潜伏期是未知的。 我们发现许多乳腺癌表现出 当它们转移到淋巴时，其增殖率显著降低 结 我们假设淋巴结转移瘤可能作为静止肿瘤存活 沉积物，对化疗有抵抗力，能够产卵 原发病灶切除多年后复发。 一种解释可能是乳腺肿瘤依赖于 在乳房内发现但在淋巴结中不存在的生长因子。 晚 复发可能代表生长因子独立性的发展和/或 迁移到新的生长因子富集区（例如，肝或骨髓）。 我们 该提案旨在确定增殖率和生长因子的作用 在乳腺癌不寻常的自然史中， 并作为潜在的治疗靶点。 在目标I中，我们将开发大型（>300 患者）乳腺癌患者的队列，并使用新的 组织微阵列技术。 这些队列将包括匹配的 来自原发病灶和淋巴结转移的组织。 我们将 检查增殖率并将其与生长因子表达相关联 和生长因子受体活化。 在Aim II中，我们将使用新鲜的 分离的组织，以确定存在于原发性肿瘤中的生长因子的量。 和淋巴结转移。 目的III将分析初级人类的反应 乳腺肿瘤的外源性生长因子，集中在增殖 以及其他肿瘤活化的下游标志物。 所有结果 目标将与患者存活率和复发率相关。 本研究的主要研究者是Robert L.坎普医学博士哲学博士、谁 最近完成了在耶鲁纽黑文医院的病理学实习。 坎普博士有兴趣从事转化研究， 专注于更好的癌症诊断工具， 技术来确定个体肿瘤的适当治疗。 本提案的导师是医学博士大卫里姆，哲学博士、谁是一个既定的 耶鲁大学病理学系的研究员和细胞病理学家 大学。 里姆博士在基础和 翻译研究 拟议的研究地点， 病理学，既有智力和物质资源，以支持博士。 坎普的研究，并包含高质量的调查人员和“国家的- “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.