MOLECULAR MARKERS FOR HIGH RISK OF BREAST CANCER

这些研究的主要目标是开发出预测 导管原位癌（DCIS）病例将复发和/或变得侵袭性， 有助于乳腺X线检查发现的DCIS的临床管理。 做 我们将研究单纯DCIS和与浸润性DCIS相关的病例， 癌症的一些分子和免疫组织化学标记， 在侵袭性癌症中是异常的。包括在 评估的是杂合性丢失（洛）和基因扩增， 各种染色体位点，各种免疫组织化学标记 与侵袭以及与失调相关的标志物 增殖和凋亡。 第二个目标是进行初步研究， 非恶性上皮细胞中的标志物， 很可能会发展成癌症这些研究将集中在 表征形态学上的非恶性乳腺上皮 邻近恶性肿瘤，将该组织与真正正常的乳腺癌进行比较， 上皮和患者的其它组织（即，皮肤与乳房 上皮）。如果这些研究能够成功地鉴定出 邻近恶性肿瘤的非恶性上皮细胞的畸变，未来 超出提案范围的研究可以评估标记物的有效性 当与其他诊断药物联合使用时， 例如针吸和/或随机乳头活检。 此外，这些标记物可能在化学预防试验中替代 目前使用的恶性肿瘤终点，这将允许试验 用更少的病人和更短的时间进行。

The major goal of these studies is to develop markers predictive of which ductal carcinoma in situ (DCIS) cases will recur and/or become invasive to aid in the clinical management of mammographically-detected DCIS. To do this we will examine cases of pure DCIS and DCIS associated with invasive cancers for a number of molecular and immunohistochemical markers known to be abnormal in invasive cancers. Included among the markers to be evaluated are loss of heterozygosity (LOH) and gene amplification at various chromosomal loci, various immunohistochemical markers associated with invasion as well as markers associated with dysregulated proliferation and apoptosis. A second goal is to undertake preliminary studies to identify molecular markers in nonmalignant epithelium that might distinguish those cases likely to progress to cancer. These studies will concentrate on characterizing the morphologically nonmalignant mammary epithelium adjacent to malignancies, comparing this tissue to truly normal mammary epithelium and to other tissues of the patient (i.e., skin vs. mammary epithelium). If these studies are successful in identifying molecular aberrations in nonmalignant epithelium adjacent to malignancy, future studies beyond the scope of the proposal could evaluate marker efficacy for early diagnosis when used in combination with other diagnostic modalities such as needle aspirates and/or random nipple biopsies. Additionally, such markers mabe surrogates in chemoprevention trials for the currently used endpoint of malignancy which would allow trials to be performed with fewer patients and over shorter time periods.