Primary Hormonal Therpay for DCIS of the Breast

描述（由申请人提供）：这个指导职业发展奖将提供奖学金培训的外科肿瘤学家进行翻译研究评估非手术治疗前乳腺癌的选择的基本支持。 患者将从NIH指定的综合癌症中心内的三级护理多学科乳腺诊所以及附属城市县医院获得。 导管原位癌（DCIS）今年将在美国超过50，000名妇女中被诊断出来。 尽管DCIS的转移可能性很小，但目前DCIS的乳房手术与浸润性乳腺癌的手术没有区别。 以前不可能对DCIS患者采用非手术方法，因为没有跟踪DCIS的工具。这项前瞻性临床试验将确定绝经后妇女术前使用芳香酶抑制剂（AI）进行激素治疗是否会导致MRI评估的DCIS肿瘤体积减少。 次要终点将包括免疫组织化学（IHC）和基因组反应标志物的变化。 本研究将招募40例经芯活检诊断为DCIS且无并发浸润性癌症的绝经后患者。 合格女性将在研究开始时接受基线乳腺X线摄影和MR检查，并在AI治疗3个月后再次接受。 主要终点将是通过MRI测量的肿瘤体积和肿瘤直径。 将在基线和手术切除时评估由肿瘤的IHC和基因组特征组成的生物标志物，以确定缓解的预测和预后标志物。 虽然目前对DCIS的侵入性治疗是有效的，但它们可能代表了至少一半患有DCIS的女性的过度治疗，这些女性可能永远不会进展为侵袭性癌症。 该提案的长期目标是有效地改变DCIS的治疗方法，以便至少对一部分患者采用非手术干预（如激素治疗）代替乳房肿瘤切除术和放射治疗或乳房切除术。 该项目将提供一个难得的机会，直接评估DCIS对治疗的临床和生物学反应，而不影响患者安全或癌症治疗。通过患者参与此类研究，我们可以为计划针对乳腺癌早期表现患者的新型、侵袭性较低的治疗算法奠定基础。 我们相信，为这组患者量身定制的策略不仅是可能的，而且比目前提供的治疗更合适。如果患者能够安全地避免癌症进展，同时避免DCIS的手术和放射的发病率，那么早期乳腺癌检测的全部益处就可以实现。

DESCRIPTION (provided by applicant): This Mentored Career Development Award will provide the essential support for a fellowship-trained surgical oncologist to conduct a translational research study evaluating nonsurgical options for preinvasive breast cancer. Patients will be accrued from a tertiary care multidisciplinary breast clinic housed within an NIH designated comprehensive cancer center as well as from an affiliated urban county hospital. Ductal carcinoma in situ (DCIS) will be diagnosed in over 50,000 women in the United States this year. Current breast surgery for DCIS does not differ from that undertaken for invasive breast cancer, despite the minimal metastatic potential for DCIS. A nonsurgical approach in patients with DCIS has previously not been possible as there has been no tool with which to follow DCIS. This prospective clinical trial will determine whether a course of preoperative hormonal therapy with an aromatase inhibitor (AI) in postmenopausal women results in a decrease in DCIS tumor volume as assessed by MRI. Secondary endpoints will consist of changes in immunohistochemical (IHC) and genomic markers of response. 40 postmenopausal patients diagnosed with DCIS on core biopsy without concurrent invasive cancer will be recruited for the study. Eligible women will undergo baseline mammography and MR] at study initiation and again following 3 months of treatment with an AI. Primary endpoints will be tumor volume and tumor diameter, as measured by MRI. Biomarkers consisting of IHC and genomic characteristics of the tumor will be assessed at baseline and at surgical excision to identify predictive and prognostic markers of response. While the current invasive treatments for DCIS are effective, they could represent overtreatment of at least half the women with DCIS who might never progress to invasive cancer. The long-term goal of this proposal is to effectively alter the treatment algorithm of DCIS so that nonsurgical interventions such as hormonal therapy could be instituted in the place of lumpectomy and radiation or mastectomy for at least a subset of patients. This project will provide a rare opportunity to directly evaluate both the clinical and biological response of DCIS to therapy without compromising patient safety or cancer treatment. Through patient participation in such studies, we can establish a foundation from which to plan novel, less aggressive treatment algorithms for patients with the earliest manifestations of breast cancer. We believe that a more tailored strategy for this group of patients is not only possible, but more appropriate than currently offered treatments. If patients could safely be spared from cancer progression while avoiding the morbidity of surgery and radiation for DCIS, the full benefit of early breast cancer detection could be realized.