Primary Hormonal Therpay for DCIS of the Breast

描述(由申请者提供)：这个有指导的职业发展奖将为一名接受过奖学金培训的外科肿瘤学家提供必要的支持，以进行一项转化性研究，评估浸润性乳腺癌前的非手术治疗方案。患者将从NIH指定的综合癌症中心内的三级保健多学科乳房诊所以及附属的城市县医院获得。 今年，美国将有5万多名女性被诊断为导管原位癌(DCIS)。尽管DCIS的转移潜力很小，但目前DCIS的乳房手术与浸润性乳腺癌的手术没有什么不同。对于DCIS患者的非手术方法以前是不可能的，因为一直没有工具可以用来跟踪DCIS。这项前瞻性临床试验将确定绝经后妇女在手术前使用芳香酶抑制剂(AI)进行一个疗程的激素治疗是否会导致MRI评估的DCIS肿瘤体积的减少。次要终点包括免疫组织化学(IHC)和基因组反应标记物的变化。 40名绝经后经核心活检确诊为DCIS但无并发浸润性癌的患者将被纳入研究。符合条件的女性将在研究开始时接受基线乳房X光检查和MR]，并在接受人工智能治疗3个月后再次接受。MRI测量的主要终点是肿瘤体积和肿瘤直径。由IHC和肿瘤基因组特征组成的生物标记物将在基线和手术切除时进行评估，以确定预测和预测反应的标记物。 虽然目前对DCIS的侵袭性治疗是有效的，但它们可能代表着至少一半患有DCIS的女性过度治疗，这些女性可能永远不会发展为浸润性癌症。这项提议的长期目标是有效地改变DCIS的治疗算法，以便可以在肿块切除和至少一部分患者的放射或乳房切除的地方开始非手术干预，如激素治疗。该项目将提供一个难得的机会，在不影响患者安全或癌症治疗的情况下，直接评估DCIS对治疗的临床和生物学反应。通过患者参与这样的研究，我们可以建立一个基础，在此基础上为乳腺癌最早表现的患者计划新的、侵略性较小的治疗算法。我们认为，为这类患者量身定做一种策略不仅是可能的，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，同时避免手术和放射治疗DCIS的并发症，那么乳腺癌早期检测的全部好处就可以实现。

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.