Together: Transforming and Translating Discovery to Improve Health

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，佛罗里达大学从四个国家合作社获得了数据 团体试验表明，对于接受新辅助化疗的乳腺癌患者， 患有残留乳房疾病(YPT)的女性总体存活率明显较低 更严重的远处复发，即使腋窝有病理完全反应(ApCR)。 I级证据表明区域淋巴结照射(RNI)可改善无远处转移 高危结节阴性疾病和临床高危妇女的生存率和总体生存率 结节阳性疾病。然而，新辅助化疗混淆了明确的指征 RNI和I级证据表明该治疗策略正在进行中；在缺乏I级数据的情况下，许多 使用apCR来指导决策。为此，我们的建议包括一项三目标战略，以确定 回顾(目标1)和前瞻性(目标2)RNI是否改善患者的总存活率 与YPT乳腺癌和(Aim3)确定是否以及如何纵向变化的循环 肿瘤DNA(CtDNA)在乳腺癌治疗中的应用 结果。对于目标2和目标3，具体的分目标是评价以下各项的比较结果 黑人女性和非西班牙裔白人。我们将通过以下方式实现这些目标 全国协作组资料的回顾性分析，一项介入性单臂II期试验 对患有YPT病的妇女进行RNI治疗，并对接受治疗的妇女进行前瞻性队列研究 乳腺癌的治疗从新辅助化疗开始。目标2和3是 互补性，使女性可以参加一项或两项试验，允许在 第二个目标是更好地探索不同的治疗方法如何影响ctDNA。目标1：评估 在NSABP B-40和B-41试验中，接受新辅助治疗的妇女接受放射治疗。目标2： 评价区域结节放疗对术后残留乳腺疾病患者的疗效 新辅助化疗。次级目标2：确定放射性核糖核酸对残留乳房的妇女是否有好处 新辅助化疗后的疾病在黑人女性和非西班牙裔白人之间的差异 女人。目的3：检测PIK3CA患者血液循环肿瘤DNA的纵向变化 突变的浸润性乳腺癌在完成所有三种治疗方式的过程中 新辅助化疗--手术-区域淋巴结放疗。次级目标3：对妇女进行测量 侵袭性PIK3CA突变乳腺癌接受循环肿瘤DNA的三模式治疗 她们的变化在黑人女性和非西班牙裔白人女性中有所不同。 17

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