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

摘要：黑人女性的乳腺癌预后低于非西班牙裔白人女性。 此外，佛罗里达大学还获得了四个国家合作社的数据 团体试验表明，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明显较差 即使腋窝病理完全缓解（apCR），也会出现更严重的远处复发。 I 级证据表明区域淋巴结照射 (RNI) 可改善无远处转移 患有高风险淋巴结阴性疾病的女性的生存率和总体生存率以及临床 淋巴结阳性疾病。然而，新辅助化疗混淆了明确的适应症 RNI 和治疗策略的 I 级证据正在等待中；在缺乏一级数据的情况下，许多 使用 apCR 来指导决策。为此，我们的建议包括一项三目标战略，以确定 回顾性（目标 1）和前瞻性（目标 2）RNI 是否可以改善患者的总生存期 ypT+ 乳腺癌并（目标 3）确定循环中是否存在纵向变化以及如何变化 三联乳腺癌治疗中的肿瘤 DNA (ctDNA) 与癌症相关 结果。对于目标 2 和 3，具体的子目标是评估之间的比较结果 黑人女性和非西班牙裔白人女性。我们将通过以下方式实现这些目标 国家合作组数据回顾性分析，一项介入性单臂II期试验 患有 ypT+ 疾病的女性的 RNI 的影响，以及接受治疗的女性的前瞻性队列研究 从新辅助化疗开始的乳腺癌治疗。目标 2 和 3 是 互补性使得妇女可以参加一项或两项试验，从而允许试验中存在异质性 第二个目标是更好地探索不同治疗方法如何影响 ctDNA。目标 1：评估治疗的益处 NSABP 试验 B-40 和 B-41 中接受新辅助治疗的女性接受放射治疗。目标 2： 评估局部淋巴结照射对患有残留乳腺疾病的女性的益处 新辅助化疗。子目标 2：确定 RNI 对残留乳房的女性是否有益 黑人女性和非西班牙裔白人新辅助化疗后的疾病存在差异 女性。目标 3：纵向测量 PIK3CA 女性循环肿瘤 DNA 的变化 突变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->局部淋巴结照射。子目标 3：衡量女性 患有侵袭性 PIK3CA 突变乳腺癌，如果循环肿瘤 DNA，则接受三联治疗 黑人女性和非西班牙裔白人女性的变化有所不同。 17 号