Together: Transforming and Translating Discovery to Improve Health

共同努力：转变和转化发现以改善健康

• 批准号: 10294560
• 负责人: DUANE A. MITCHELL
• 金额: $ 19.51万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10294560
• 关键词: Affect; Axilla; Blood Tests; Breast; Breast Cancer Treatment; Breast Diseases; Cancer Control; Caring; Clinical; Data; Disease; Disease-Free Survival; Distant Metastasis; Enrollment; Florida; Goals; Health; In complete remission; Inferior; Learning; Malignant Neoplasms; Measures; Modality; Mutate; National Surgical Adjuvant Breast and Bowel Project; Neoadjuvant Therapy; Nodal; Not Hispanic or Latino; Operative Surgical Procedures; Outcome; PIK3CA gene; Pathologic; Patients; Positive Lymph Node; Radiation therapy; Recurrence; Residual state; Therapeutic; Translating; Universities; Woman; arm; black women; chemotherapy; comparative; curative treatments; draining lymph node; high risk; improved; irradiation; malignant breast neoplasm; phase II trial; prospective; tumor DNA

Abstract: Breast cancer outcomes for Black women are inferior to their white non-Hispanic counterparts. In addition, the University of Florida obtained data from four national cooperative group trials demonstrating that for patients with breast cancer who receive neoadjuvant chemotherapy, womenwho have residual breast disease (ypT+) have significantly inferior overall survival and worsedistant recurrence, even with a pathologic complete response in the axilla (apCR). Level I evidencedemonstrates regional nodal irradiation (RNI) improves distant metastasis-free survival and overallsurvival for women with high risk node negative disease and clinical node-positive disease. However,neoadjuvant chemotherapy has obfuscated the clear indications for RNI and level I evidence with thattreatment strategy ispending; in the absence of level I data, many use apCR to guide decisions. To thatend, our proposal consists of a three-aimed strategy to determine retrospectively (Aim 1) and prospectively (Aim 2) if RNI improves overall survival in patients with ypT+ breast cancer and (Aim3) determine if and how longitudinal changes in circulating tumor DNA (ctDNA) across trimodality breastcancer curative treatment associate with cancer outcome. For Aims 2 and 3,specific sub-aimsare to evaluate comparative outcomes between Black women and non-Hispanic white counterparts.We will realize these goals through retrospective analysis of national cooperative group data, aninterventional single-arm phase II trial of RNI for women with ypT+ disease, and a prospective cohortstudy of women receiving curative breast cancer treatment beginning with neoadjuvant chemotherapy.Aims 2 and 3 are complementary such that women can enroll in one or both trials, allowing forheterogeneity in the second aim to better explore how different treatments may affect ctDNA.Aim 1: Evaluate the benefit of radiotherapy in women treated with neoadjuvant therapy on NSABP trials B-40 and B-41. Aim 2: Evaluate the benefit of regional nodal irradiation in women withresidual breast disease after neoadjuvant chemotherapy. Sub-Aim 2: Determine if the benefit of RNIin women with residual breast disease after neoadjuvant chemotherapy differs between Black womenand non-Hispanic white women. Aim 3: Measure the change in circulating tumor DNA longitudinallyfor women with PIK3CA mutated invasive breast cancer completing all three modalities of treatment inthe course of neoadjuvant chemotherapy -> surgery -> regional nodal irradiation. Sub-Aim 3: Measurein women with invasive PIK3CA mutated breast cancer receiving triple modality care if circulating tumorDNA their change differ between Black women and non-Hispanic whitewomen. 17

翻译后摘要：黑人妇女乳腺癌的结果是不如他们的白色非西班牙裔同行。 此外，佛罗里达大学从四个国家合作组织获得了数据， 组试验表明对于接受新辅助化疗的乳腺癌患者， 患有残留乳腺疾病（ypT+）的女性的总体生存率显著降低 远处复发率更低，甚至腋窝病理完全缓解（apCR）。 I级证据表明区域淋巴结照射（RNI）可改善无远处转移 高危淋巴结阴性疾病妇女的生存率和总体生存率 淋巴结阳性疾病然而，新辅助化疗混淆了明确的适应症， RNI和I级证据与治疗策略尚待确定;在缺乏I级数据的情况下，许多 使用apCR来指导决策。为此，我们的建议包括三个目标的战略，以确定 回顾性（目标1）和前瞻性（目标2）RNI是否可改善患者的总生存期 与ypT+乳腺癌和（Aim 3）确定是否和如何纵向变化，在循环 肿瘤DNA（ctDNA）与癌症相关三种乳腺癌治疗方法 结果。对于目标2和目标3，具体的子目标是评价 黑人妇女和非西班牙裔白色同行。我们将实现这些目标，通过 国家合作组数据的回顾性分析，一项干预性单臂II期试验 ypT+疾病女性的RNI，以及接受治疗的女性前瞻性队列研究 乳腺癌治疗从新辅助化疗开始。目标2和3是 互补，这样女性可以参加一项或两项试验，允许异质性， 第二个目的是更好地探索不同的治疗方法如何影响ctDNA。目的1：评估 NSABP试验B-40和B-41中接受新辅助治疗的女性中的放疗。目标二： 局部淋巴结照射对乳腺癌术后残留乳腺的疗效评价 新辅助化疗子目标2：确定RNI在残留乳房女性中的获益 新辅助化疗后的疾病在黑人女性和非西班牙裔白色女性之间存在差异 妇女目的3：测量PIK 3CA女性患者循环肿瘤DNA的变化 突变的浸润性乳腺癌在治疗过程中完成所有三种治疗方式， 新辅助化疗->手术->局部淋巴结放疗。次级目标3：衡量妇女 侵袭性PIK 3CA突变的乳腺癌患者如果循环肿瘤DNA 他们的变化在黑人妇女和非西班牙裔白人妇女之间存在差异。 17