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

项目摘要/摘要 前哨淋巴结活检(SLNB)，包括切除最初几个引流的淋巴结，是 临床结节阴性(CN0)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，发病率极低。在临床患者中 阳性结节、腋窝淋巴结清扫(ALND)或大部分腋窝淋巴结切除 曾经的标准护理；然而，NAC可以根除腋下结节的疾病，具有结节病理 完全应答率(PCR)为40%，从而减少了对ALND的需求，从而将风险降至最低 淋巴水肿的症状。最初的小规模回顾研究表明，SLNB在这一人群中是不准确的， 假阴性率为21%~33%。最近，4项前瞻性多机构试验显示， 出现局限性腋窝淋巴结转移(CN1)的患者可以可靠地在NAC后进行SLNB分期， 使用双示踪标测和检索≥3前哨淋巴结，FNRS为10%。病人 表现为局部晚期乳腺癌(LABC)-定义为乳腺皮肤或胸部疾病 脑室壁受累(CT4)和/或结节广泛病变(CN2/N3)--不被认为是候选对象 对于SLNB，由于其在提出时的沉重疾病负担，以及SLNB准确的证据有限 在这个患者群体中排在NAC之后。此外，据推测，患者的实质性肿瘤负担 使用LABC会导致PCR率对NAC的比率较低，从而排除了手术的降级。然而，最近的一次 纪念斯隆-凯特琳癌症中心治疗的321例LABC患者的回顾性研究 结节PCR率高(38%)，cN1患者(43%)，CN2患者(36%)， CN3病(32%)(p=0.23)。现代NAC对患者肿瘤负担的减轻幅度 LABC的报告表明，相当数量的女性可能无法从ALND中受益，而可能会 遭受不必要的病痛。这些患者可能是NAC后SLNB的候选患者，条件是 该程序可准确预测该人群的腋窝结节状态。我们假设一种严重的疾病 初诊时乳房或区域结节的负担不是SLNB的禁忌症 随着NAC的出现，疾病被降级了。我们建议进行一项多机构、前瞻性、单臂试验来评估 LABC患者NAC后行SLNB的可行性和FNR。符合条件的患者的疾病是 NAC后还原为cN0的患者将接受SLNB和双示踪标测，然后进行ALND以评估FNR SLNB。研究结果可能导致腋窝NAC后的外科治疗取得重大进展 减少了对ALND的需求，提高了幸存者的生活质量。

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.