GENETIC STAGING OF BREAST CANCERS FOR ADJUVANT THERAPY

乳腺癌基因分期辅助治疗。 整体 本研究的目的是阐明遗传过程， 是人类乳腺癌生长和临床进展的基础， 为患者的选择提供可靠的生物学依据 有早期临床疾病的人复发的风险高， 可能会从辅助治疗中受益。 我们会研究 HER-2/neu与H-ras相互关系 扩增/过表达，以及癌基因 过表达和流式细胞术非整倍体。 我们的具体目标是：1） 比较HER-2/neu和H-ras检测的敏感性 通过流式细胞术和流式细胞仪检测早期乳腺癌中的过度表达， 传统的分子遗传技术; 2）确定是否有数量 遗传异常，或其细胞分布（多个 在相同细胞或不同细胞中表达的癌基因）是 生物学和临床意义，3）检查癌基因的程度 与肿瘤侵袭性相关的每个细胞的过表达，以及 确定高水平HER-2/neu和H-ras过表达是否是由于 增加每个细胞携带癌基因的染色体拷贝数，以及4） 为了确定癌基因过表达是否优先发生在 通过多参数流式细胞术检测非整倍体细胞。 的 应用常规分子遗传学技术，多参数 流式细胞术和染色体特异性探针研究， 同样的肿瘤应该提供一个全面的遗传观点， 乳腺癌的进化变化。 临时分期系统是 这是基于在人类中发现的遗传进化程度。 原发性肿瘤 该分期系统的临床有效性， 特别是，它在识别那些表面上 最有可能从辅助治疗中获益的早期临床疾病 将根据临床肿瘤侵袭性评估治疗， 通过长期临床随访研究确定。

Genetic Staging of Breast Cancers for Adjuvant Therapy. The overall objectives of this study are to elucidate the genetic processes that underlie the growth and clinical progression of human breast cancers, in order to provide a sound biological basis for the selection of patients with early clinical disease who are at high risk for recurrence, and who might benefit from adjuvant therapy. We will examine the interrelationship between HER-2/neu and H-ras amplification/overexpression, and the relationship between oncogene overexpression and flow cytometric aneuploidy. Our specific aims are: 1) to compare the sensitivity of detection of HER-2/neu and H-ras overexpression in early breast cancer by flow cytometry and by conventional molecular genetic techniques; 2) to determine if the number of genetic abnormalities, or their cellular distribution (multiple oncogenes expressed in the same cells or in different cells) are of biological and clinical importance, 3) to examine the degree of oncogene overexpression per cell in relation to tumor aggressiveness, and to determine if high levels of HER-2/neu and H-ras overexpression are due to, increased oncogene-bearing chromosome copy numbers per cell, and 4) to determine if oncogene overexpression occurs preferentially in aneuploid cells by means of multiparameter flow cytometry. The application of conventional molecular genetic techniques, multiparameter flow cytometry, and chromosome-specific probe studies to cells from the same tumors should provide a comprehensive view of the genetic evolutionary changes in breast cancer. A provisional staging system is proposed, .that is based on the degree of genetic evolution found in the primary tumor. The clinical validity of this staging system, and, in particular, its usefulness in identifying those patients with ostensibly early clinical disease who are most likely to benefit from adjuvant therapy will be assessed in relation to clinical tumor aggressiveness, as determined by long-term clinical followup studies.