Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Patients Presenting with Locally Advanced Breast Cancer: A Prospective Study

局部晚期乳腺癌患者新辅助化疗后前哨淋巴结活检：一项前瞻性研究

• 批准号: 10502586
• 负责人: Andrea Barrio
• 金额: $ 8.85万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10502586
• 关键词: Axilla; Axillary Lymph Node Dissection; Axillary lymph node group; Biopsy; Breast; Chest wall structure; Clinical; Clip; Colloids; Combined Modality Therapy; Data; Databases; Diagnosis; Disease; Dyes; Excision; Failure; Feasibility Studies; Frequencies; Future; Goals; Grant; In complete remission; Institutes; Isosulfan Blue; Lead; Locally Advanced Malignant Neoplasm; Lymphedema; Memorial Sloan-Kettering Cancer Center; Methods; Modernization; Morbidity - disease rate; Neoadjuvant Therapy; Neoplasm Metastasis; Nodal; Operative Surgical Procedures; Pathologic; Patients; Pilot Projects; Policies; Population; Positive Lymph Node; Preparation; Procedures; Prospective Studies; Quality of life; Research; Retrieval; Retrospective Studies; Sentinel Lymph Node; Sentinel Lymph Node Biopsy; Skin; Staging; Sulfur; Surgical Management; Survivors; Technetium 99m; Time; Tracer; Tumor Burden; Widespread Disease; Woman; advanced breast cancer; advanced disease; arm; burden of illness; chemotherapy; draining lymph node; follow-up; improved; malignant breast neoplasm; patient population; patient subsets; prospective; risk minimization; standard of care; tumor

Project Summary/Abstract Sentinel lymph node biopsy (SLNB), which involves removal of the first few draining lymph nodes, is the standard method for staging the axilla in patients with clinically node-negative (cN0) breast cancer undergoing neoadjuvant chemotherapy (NAC) and is widely accepted, with minimal morbidity. In patients with clinically positive nodes, axillary lymph node dissection (ALND), or removal of the majority of axillary lymph nodes, was once the standard of care; however, NAC can eradicate disease in the axillary nodes, with nodal pathologic complete response (pCR) rates of 40%, thus reducing the need for ALND and consequently minimizing the risk of lymphedema. Initial small retrospective studies showed that SLNB was inaccurate in this population, with false-negative rates (FNRs) of 21%-33%. More recently, 4 prospective multi-institutional trials showed that patients presenting with limited axillary nodal metastases (cN1) can be reliably staged with SLNB after NAC, with FNRs of <10% with the use of dual-tracer mapping and retrieval of ≥3 sentinel lymph nodes. Patients presenting with locally advanced breast cancer (LABC)—defined as disease in the breast with skin or chest wall involvement (cT4) and/or extensive disease in the nodes (cN2/N3)—have not been considered candidates for SLNB, owing to their heavy disease burden at presentation and the limited evidence that SLNB is accurate after NAC in this patient population. Furthermore, it was presumed that the substantial tumor burden in patients with LABC would result in low rates of pCR to NAC, precluding surgical downstaging. However, a recent retrospective study of 321 patients with LABC treated at Memorial Sloan Kettering Cancer Center demonstrated high nodal pCR rates (38%), with similar rates between patients with cN1 (43%), cN2 (36%), and cN3 (32%) disease (p=0.23). The magnitude of reduction in tumor burden with modern NAC in patients presenting with LABC suggests that a substantial number of women may not benefit from ALND and may be subjected to unnecessary morbidity. These patients may be candidates for SLNB after NAC, provided that the procedure accurately predicts axillary nodal status in this population. We hypothesize that a heavy disease burden in the breast or the regional nodes at presentation is not a contraindication to SLNB in patients whose disease is downstaged with NAC. We propose a multi-institutional, prospective, single-arm trial to evaluate the feasibility and FNR of SLNB after NAC in patients presenting with LABC. Eligible patients whose disease is reduced to cN0 after NAC will undergo SLNB with dual-tracer mapping followed by ALND to assess the FNR of SLNB. Study findings could lead to significant advances in the surgical management of the axilla after NAC in patients with LABC, reducing the need for ALND and improving quality of life of survivors.

项目概要/摘要 前哨淋巴结活检 (SLNB) 涉及切除前几个引流淋巴结，是 临床淋巴结阴性 (cN0) 乳腺癌患者腋窝分期的标准方法 新辅助化疗（NAC）在临床患者中被广泛接受，发病率极低。 阳性淋巴结，轴向淋巴结清扫术（ALND），或切除大部分轴向淋巴结， 一旦达到护理标准；NAC 可以根除腋窝淋巴结的疾病，并伴有淋巴结病理 完全缓解 (pCR) 率为 40%，从而减少 ALND 的需求，从而将风险降至最低 最初的小型回顾性研究表明，SLNB 在该人群中并不准确。 最近，4 项前瞻性多机构试验表明，假阴性率 (FNR) 为 21%-33%。 出现局限性腋窝淋巴结转移 (cN1) 的患者可以在 NAC 后通过 SLNB 进行可靠分期， 使用双示踪剂标测和检索≥3个前哨淋巴结的患者，FNR<10%。 患有局部晚期乳腺癌 (LABC)——定义为乳房皮肤或胸部疾病 壁受累 (cT4) 和/或淋巴结广泛病变 (cN2/N3) - 尚未被视为候选者 对于 SLNB，由于其就诊时的疾病负担很重，并且证明 SLNB 准确的证据有限 此外，据推测，在该患者群体中进行 NAC 后，患者的肿瘤负担也很大。 LABC 会导致 NAC 的 pCR 率较低，从而无法进行手术降期。 对纪念斯隆凯特琳癌症中心治疗的 321 名 LABC 患者进行的回顾性研究 显示出较高的淋巴结 pCR 率 (38%)，cN1 (43%)、cN2 (36%)、 和 cN3 (32%) 疾病（p=0.23）。 LABC 的演示表明，大量女性可能无法从 ALND 中受益，并且可能会 这些患者可能是 NAC 后 SLNB 的候选者，前提是 程序准确地预测了该人群的腋窝淋巴结状况，我们发现了这种严重的疾病。 对于以下患者，乳房或区域淋巴结有负担并不是 SLNB 的禁忌症： 我们提出了一项多机构、前瞻性、单臂试验来评估疾病的分期。 对于符合条件的 LABC 患者，NAC 后 SLNB 的可行性和 FNR。 NAC 将接受双示踪剂映射的 SLNB，然后进行 ALND 以评估 FNR 后降低至 cN0 研究结果可能会导致 NAC 后腋窝手术治疗的重大进展。 LABC 患者，减少 ALND 的需要并提高幸存者的生活质量。