GENETIC STAGING OF BREAST CANCERS FOR ADJUVANT THERAPY

乳腺癌的基因分期用于辅助治疗。整体而言 这项研究的目的是阐明 是人类乳腺癌生长和临床进展的基础， 以便为患者的选择提供良好的生物学基础 有早期临床疾病的人复发的风险很高，以及 可能从辅助治疗中受益。我们将研究 HER-2/neu与H-ras的相互关系 扩增/过表达及其与癌基因的关系 过表达和流式细胞术非整倍体。我们的具体目标是：1) 检测HER-2/neu和H-ras的敏感性比较 流式细胞术和免疫组织化学方法检测早期乳腺癌中的过度表达 常规分子遗传学技术；2)确定数量是否 遗传异常或其细胞分布(多个 在同一细胞或不同细胞中表达的癌基因)是 生物学和临床意义，3)检测癌基因的程度 每个细胞过度表达与肿瘤侵袭性的关系，以及 确定HER-2/neu和H-ras的高水平过度表达是否是原因 To，每细胞携带癌基因的染色体拷贝数增加，以及4) 为了确定癌基因过度表达是否优先发生在 多参数流式细胞术检测异倍体细胞。这个 多参数常规分子遗传学技术的应用 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对基因的全面观察 乳腺癌的进化变化。临时分段系统是 提出，这是基于基因进化的程度在 原发肿瘤。该分期系统的临床有效性，以及 特别是，它在识别那些表面上有 最有可能受益于佐剂的早期临床疾病 治疗将根据临床肿瘤侵袭性进行评估，如 由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.