BREAST CANCER

NCCTG的乳腺癌项目致力于具有临床意义的研究，这些研究解决了对患有这种疾病的所有阶段的女性来说重要的管理问题。此外，对实验室相关科学研究的重视程度也有所提高。患者对治疗方案的应计费用从上一个五年赠款期间的每年314名患者增加到本赠款期间的每年484名患者。自1996年1月1日以来，已出版16篇稿件和10篇摘要。乳房计划的主要成就包括四个方面：1)转移性乳腺癌(MBC)的新激素治疗方法：我们展示了两个剂量表的来曲唑的抗肿瘤活性；他莫昔芬和来曲唑之间缺乏药代动力学相互作用；共同赞助的一项乳房组间研究显示，对绝经前患者进行内科和外科去势治疗具有类似的益处；2)治疗MBC的新化疗方法。我们证实了紫杉醇联合卡铂的显著抗肿瘤活性；在一项随机的II期试验中证实了不同序贯方案的AC-多西紫杉醇化疗的活性，该试验还包括对可溶性HER-1和HER-2受体的翻译分析；共同赞助的PBT-1组间试验证明，与常规化疗相比，接受大剂量干细胞支持化疗的患者缺乏生存改善；共同赞助的E1193组间试验表明，同时使用紫杉醇和阿霉素而不是顺序使用这些药物可以改善应答率和进展时间；3)新的放射治疗方法：我们论证了对早期乳腺癌患者进行超分割放射治疗的可行性，并将治疗时间缩短至3周，无论是否使用阿霉素；4)辅助治疗：我们共同赞助了三个组间试验，INT 0100，证明辅助化疗-他莫昔芬与单用他莫昔芬对绝经后结节阳性乳腺癌患者的无瘤生存率和总生存率的改善，以及S9313和C9741研究，评估了结节(+)或结节(-)乳腺癌的化疗顺序和剂量。未来计划：1)MBC的激素治疗：评估他莫昔芬联合曲妥珠在ER(-)转移性乳腺癌患者中的活性(通过4E HER-1和HER-2受体的翻译评估)和作为三线激素治疗的纯抗雌激素药物Faslodex；2)MBC的新化疗方法：我们将协调N9931组间试验，以评估单抗曲妥珠单抗对HER-2表达水平较低(+1，+2)患者的化疗疗效(包括生活质量分析和相关科学研究)，多西紫杉醇和卡铂作为一线治疗方案的研究(以及可能与反应和毒性相关的基因多态性的翻译评估)；MTA联合吉西他滨的评估；局部神经酰胺的评估和乳腺癌皮肤转移患者的生活质量；我们正在进行的多司他丁-10、伊立替康、口服依托泊苷与静脉注射紫杉醇联合治疗晚期乳腺癌的试验以及针对Her2-2(+3)高表达患者的紫杉醇、卡铂和曲妥珠单抗的优化时间表已经完成；3)辅助治疗：我们将协调新的乳房组间辅助剂的使用。正在开发其他新的治疗方法，包括免疫治疗和具有适当相关翻译研究的其他生物疗法。乳房计划的成就和未来计划阐述了NCCTG作为一个整体的主要研究主题，即新疗法、第二阶段试验、转化研究、参与和协调国家小组间研究、生活质量以及社区医生积极参与所有方面的试验。

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.