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

项目总结/摘要 前哨淋巴结活检（SLNB），其中包括去除前几个引流淋巴结，是最好的方法。 临床淋巴结阴性（cN 0）乳腺癌患者腋窝分期的标准方法， 新辅助化疗（NAC）被广泛接受，发病率最低。在临床上 阳性淋巴结、腋窝淋巴结清扫术（ALND）或切除大部分腋窝淋巴结， 一旦护理标准;然而，NAC可以根除腋窝淋巴结中的疾病， 完全缓解（pCR）率为40%，从而减少了对ALND的需求，从而将风险降至最低 水肿。最初的小型回顾性研究表明，SLNB在该人群中不准确， 假阴性率（FNR）为21%-33%。最近，4项前瞻性多机构试验显示， 表现为有限腋窝淋巴结转移（cN 1）的患者可以在NAC后用SLNB可靠地分期， FNR <10%，使用双示踪剂标测并回收≥3个前哨淋巴结。患者 出现局部晚期乳腺癌（LABC）-定义为乳房伴皮肤或胸部疾病 壁受累（cT 4）和/或淋巴结广泛病变（cN2/N3）-不被视为候选者 对于SLNB，由于他们在就诊时的疾病负担很重，而且SLNB准确性的证据有限， 在这一人群中，此外，据推测，患者的实质性肿瘤负荷 LABC会导致NAC的pCR率较低，排除了手术降级。但最近的一项 在纪念斯隆-凯特琳癌症中心接受治疗的321例LABC患者的回顾性研究 显示出较高的淋巴结pCR率（38%），cN 1（43%），cN2（36%）， 和cN 3（32%）疾病（p=0.23）。现代NAC在患者中的肿瘤负荷降低幅度 LABC提示，大量女性可能无法从ALND中获益， 遭受不必要的疾病。这些患者可能是NAC后SLNB的候选者，前提是 手术准确预测了该人群的腋窝淋巴结状况。我们假设一种严重的疾病 乳房或局部淋巴结负荷不是SLNB的禁忌症， 用NAC可以降低疾病的分期。我们提出了一个多机构，前瞻性，单臂试验，以评估 LABC患者NAC后SLNB的可行性和FNR。符合条件的患者，其疾病为 NAC后降至cN 0的患者将接受SLNB和双示踪剂标测，然后进行ALND，以评估 SLNB。研究结果可能导致NAC后腋窝手术治疗的重大进展， LABC患者，减少对ALND的需求，提高生存者的生活质量。

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.