BREAST CANCER

乳腺癌

• 批准号: 6563770
• 负责人: EDITH A. PEREZ
• 金额: $ 7.89万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-11 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563770
• 关键词: antineoplastics; antitumor antibody; breast neoplasms; carboplatin; combination cancer therapy; cooperative study; estrogen inhibitor; etoposide; gemcitabine; hormone therapy; human subject; human therapy evaluation; irinotecan; metastasis; monoclonal antibody; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer therapy; paclitaxel; patient oriented research; tamoxifen

The Breast Cancer Program of the NCCTG is committed to clinically meaningful research which addresses management issues important to women with all stages of this disease. There has also been an increased emphasis on laboratory correlative science studies. Patient accrual to treatment protocols has increased from 314 patients per year for the previous five-year grant period to 484 patients per year during the current grant period. Sixteen manuscripts and ten abstracts have been published since January 1, 1996. The major accomplishments of the Breast Program fall into four areas: 1) new hormonal therapy approaches for metastatic breast cancer (MBC): We demonstrated the anti-tumor activity of two dose schedules of letrozole; the lack of pharmacokinetic interaction between tamoxifen and letrozole; co-sponsored a Breast Intergroup study demonstrating similar benefit for medical versus surgical castration in pre-menopausal patients; 2) New chemotherapy approaches for MBC. We demonstrated the significant anti-tumor activity of the combination of paclitaxel plus carboplatin; the activity of different sequential schedules of AC-docetaxel chemotherapy in a randomized phase II trial which also included translational analysis of soluble Her-1 and Her-2 receptors; co- sponsored the PBT-1 intergroup trial which demonstrated a lack of survival improvement for patients receiving high dose chemotherapy with stem cell support versus conventional chemotherapy; and co-sponsored the E1193 Intergroup trial which demonstrated improved response rate and time to progression with the concurrent use of paclitaxel and adriamycin instead of the sequential use of these agents; 3) New radiotherapy approaches: We demonstrated the feasibility of hyperfractionated radiotherapy with shortening of therapy to three weeks with and without doxorubicin for patients with early stage breast cancer; 4) Adjuvant therapy: We cos-sponsored three Intergroup trials, INT 0100 which demonstrated the improvement in disease-free survival and overall survival of adjuvant chemotherapy-tamoxifen versus tamoxifen alone for post-menopausal patients with node positive breast cancer, and studies S9313 and C9741 which evaluated chemotherapy sequence and dosing in node (+) or node (-) breast cancer. Future plans: 1) Hormonal therapy for MBC: Evaluation of the activity of tamoxifen plus tratuzumub in patients with ER (-) metastatic breast cancer (with translational evaluation of solubl4e Her-1 and Her-2 receptors) and of the pure anti-estrogen Faslodex as third-line hormonal therapy; 2) New chemotherapy approaches for MBC: We will coordinate the N9931 Intergroup trial to evaluate whether the monoclonal antibody trastuzumab enhances the efficacy of chemotherapy in patients with lower degrees (+1, +2) of Her-2 expression (including quality of life analysis and correlative science studies), the study of a combination of docetaxel and carboplatin as first-line therapy (along with translational evaluation of genetic polymorphisms that may be associated with response and toxicity); the evaluation of MTA plus gemcitabine; the valuation of topical ceramides and quality of life for patients with cutaneous metastasis from breast cancer; and completion of our ongoing trials of dolastatin-10, irinotecan, and the combination of oral etoposide with intravenous paclitaxel for advanced breast cancer, as well as the optimization of schedule for paclitaxel, carboplatin, and trastuzumab for patients with higher Her2-2 (+3) expression; 3) Adjuvant therapy: We will coordinate the new Breast Intergroup adjuvant. The development of other novel therapeutic approaches, including immunotherapy and other biological therapies with appropriate correlative translational studies, is ongoing. The accomplishments and future plans of the Breast Program address the major research themes of the NCCTG as a whole; i.e., novel therapeutics, phase II trials, translational research, participation and coordination of national intergroup studies, quality of life, and active involvement of community physicians in all aspects of trials.

NCCTG的乳腺癌计划致力于临床上有意义的研究，解决对患有这种疾病的所有阶段的妇女重要的管理问题。实验室相关科学研究也越来越受到重视。治疗方案的患者累积从前一个五年补助期的每年314名患者增加到目前补助期的每年484名患者。自1996年1月1日以来，已出版了16篇手稿和10篇摘要。乳腺计划的主要成就分为四个方面：1）转移性乳腺癌（MBC）的新激素治疗方法：我们证明了来曲唑两种剂量方案的抗肿瘤活性;他莫昔芬和来曲唑之间缺乏药代动力学相互作用;共同赞助了一项乳腺组间研究，证明了绝经前患者的药物去势与手术去势的益处相似; 2）MBC的新化疗方法。我们证明了紫杉醇加卡铂联合治疗的显著抗肿瘤活性;在一项随机II期试验中AC-多西他赛化疗的不同序贯方案的活性，该试验还包括可溶性Her-1和Her-2受体的翻译分析;共同发起了PBT，1项组间试验证明，与常规化疗相比，接受高剂量化疗联合干细胞支持的患者的生存期没有改善化学疗法;并共同发起了E1193组间试验，该试验证明了同时使用紫杉醇和阿霉素而不是顺序使用这些药物改善了反应率和进展时间; 3）新的放射治疗方法：我们证明了超分割放射治疗的可行性，其中将治疗缩短至3周，有或没有阿霉素用于早期乳腺癌患者; 4）辅助治疗：我们共同赞助了三项组间试验：INT 0100，该试验证明了辅助化疗（他莫昔芬与他莫昔芬单独治疗）对淋巴结阳性乳腺癌绝经后患者的无病生存期和总生存期的改善，以及研究S9313和C9741，该研究评估了淋巴结（+）或淋巴结（-）乳腺癌的化疗顺序和剂量。未来计划：1）MBC的激素疗法：评价他莫昔芬加曲妥珠单抗在ER（-）转移性乳腺癌患者中的活性（对可溶性Her-1和Her-2受体的转化评价）和纯抗雌激素芙仕得作为三线激素治疗; 2）MBC的新化疗方法：我们将协调N9931组间试验，以评估单克隆抗体曲妥珠单抗是否增强了较低程度（+1，+2）的Her-2表达（包括生活质量分析和相关科学研究），多西他赛联合卡铂作为一线治疗的研究（沿着可能与缓解和毒性相关的遗传多态性的翻译评价）; MTA+吉西他滨的评价;局部应用神经酰胺类药物对乳腺癌皮肤转移患者生活质量的影响;并完成了我们正在进行的多拉司他汀-10、伊立替康、口服依托泊苷联合静脉紫杉醇治疗晚期乳腺癌的试验，以及紫杉醇、卡铂、和曲妥珠单抗用于Her 2 -2（+3）表达较高的患者; 3）辅助治疗：我们将协调新的乳腺组间辅助治疗。其他新的治疗方法，包括免疫疗法和其他生物疗法以及适当的相关转化研究的开发正在进行中。乳腺计划的成就和未来计划涉及整个NCCTG的主要研究主题;即，新疗法、II期试验、转化研究、国家组间研究的参与和协调、生活质量以及社区医生积极参与试验的各个方面。