STUDY OF STANDARD DOXORUBICIN AND CYCLOPHOSPHAMIDE IN ADVANCED BREAST CANCER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。1. 比较炎性和雌激素受体阴性局部晚期乳腺癌患者在G-CSF支持下每周给予阿霉素和每日口服环磷酰胺治疗与每三周给予阿霉素和环磷酰胺“标准”治疗的显微病理反应率。2. 比较这两个团的毒性。3. 比较两种方案的给药剂量强度。4. 评估这些患者原发肿瘤部位的显微病理完全缓解和临床完全缓解之间的关系。5. 为了估计治疗过程中早期遗传损伤的发生率，使用两种一般克隆测定：a) HUMARA（人类雄激素受体测定）筛选克隆造血的存在，b)微卫星不稳定性（MSI）测定筛选有缺陷的DNA错配修复机制和杂合性缺失的存在，在参加本研究的乳腺癌患者的预处理血液和三个连续治疗后标本中。6. 在HUMARA或微卫星重复检测克隆造血阳性的情况下，估计MLL（髓样淋巴细胞白血病）基因融合转录物的发生率和RAS基因突变（H-， K-和N-RAS）的频率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 1. To compare the microscopic pathologic response rates in patients with inflammatory and estrogen-receptor negative locally advanced breast cancer treated with weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support to that in patients treated with teh "standard" doxorubicin and cyclophosphamide regimen given every three weeks. 2. To compare the toxicities of these two regiments. 3. To compare the delivered dose intensity of these two regimens. 4. To assess the association between microscopic pathologic complete response and clinical complete response at the primary tumor site in these patients. 5. To estimate the incidence of early genetic damage during the course of treatment using two general clonal assays: a) the HUMARA (human androgen receptor assay) to screen for the presence of clonal hematopoiesis, and b) microsatellite instability (MSI) assays to screen for the presence of defective DNA mismatch repair mechanisms and loss of heterozygosity, in pretreatment blood and three sequential post-treatment specimens in breat cancer patients enrolled in this study. 6. To estimate the incidence of MLL (myelooid lymphoid leukemia) gene fusion transcripts and the frequency of RAS gene mutations (H-, K-, and N-RAS) in cases where either the HUMARA or microsatellite repeat assays are positive for clonal hematopoiesis.