Babar M, Madani R, Jackson P, Layer G T, Kissin M W, Irvine T E
Department of Breast and Oncoplastic Surgery, Royal Surrey County Hospital, Guildford, UK.
Department of Breast and Oncoplastic Surgery, Royal Surrey County Hospital, Guildford, UK.
Surgeon. 2016 Apr;14(2):76-81. doi: 10.1016/j.surge.2014.06.001. Epub 2014 Nov 1.
The role of sentinel lymph node micrometastases on histopathological analysis is controversial in axillary staging and management in clinically node negative breast cancer. Long-term studies addressing the clinical relevance of occult breast cancer in sentinel lymph nodes based on molecular analysis are lacking. One Step Nucleic Acid Amplification (OSNA), a highly sensitive assay of cytokeratin 19 mRNA, is used intra-operatively for the detection of lymph node macro- and micrometastases in breast cancer.
The aim of this study is to review the rate of micrometastases and further histopathological NSLN metastases, in our unit following the introduction of OSNA in Guildford.
Data was collected prospectively from the period of introduction 01/12/2008 to 31/05/2013. All patients eligible for sentinel lymph node biopsy were offered OSNA and operations were performed by the consultant breast surgeons. Presence or absence of micro-metastases depends on the agreed cut-off point on the amplification curve. On detection of micrometastases (+) and positive but inhibited (i+) metastases, a level 1 axillary clearance (ANC) was performed and for a macrometastasis (++), a level 3 ANC was carried out.
66% of the patients had negative SLN (n = 672) and 34% (n = 336) had positive sentinel lymph nodes who had further axillary surgery. Of these, 45% (n = 152/336) had macrometastases, 40% (n = 136/336) had micrometastases and 15% (48/336) had positive but inhibited results. There was no difference in the patient demographics and tumour characteristics in the various positive SLN groups. In patients with micrometastases, 15% (20/136) had further positive NLSNs and a further 6% (8/136) had >4 overall positive nodes (SLN + NSLN) thus requiring adjuvant supraclavicular/chest wall radiotherapy (p < 0.05). 25% of node positive patients had further NLSN metastases (85/336) and in these patients, the ratio of positive SLN/harvested SLN (+SLN/SLN) is constant at 1:1. This shows the likelihood of further positive NSLNs if all the harvested lymph nodes are positive. This linear trend is present in both micro-and macrometastases, thus correlating with the size and number of NSLN metastases.
Our study reflects the tumour burden of NSLNs based on the molecular analysis of the SLN. OSNA has the potential to accurately identify axillary micrometastases. Micro-metastases are important as some of the patients with micrometastases had overall four positive nodes [SLN + NSLN] (criteria for radiotherapy in the absence of other adverse clinicopathological features). Also, our study highlights certain factors that predict the NSLN metastases, pending validation by further prospective long-term data. This will allow accurate calculation of the axillary tumour burden, particularly in patients with micro-metastases.
在前哨淋巴结微转移在组织病理学分析中的作用在临床腋窝淋巴结阴性乳腺癌的分期及治疗方面存在争议。目前缺乏基于分子分析探讨前哨淋巴结隐匿性乳腺癌临床相关性的长期研究。一步核酸扩增(OSNA)是一种针对细胞角蛋白19信使核糖核酸的高灵敏度检测方法,术中用于检测乳腺癌淋巴结的宏转移和微转移。
本研究旨在回顾在吉尔福德引入OSNA后,我院前哨淋巴结微转移及进一步组织病理学非前哨淋巴结转移的发生率。
前瞻性收集2008年12月1日至2013年5月31日期间的数据。所有符合前哨淋巴结活检条件的患者均接受OSNA检测,手术由乳腺外科顾问医生进行。微转移的有无取决于扩增曲线上一致认可的临界值。检测到微转移(+)和阳性但受抑制(i+)转移时,进行一级腋窝清扫(ANC);检测到宏转移(++)时,进行三级ANC。
66%的患者前哨淋巴结阴性(n = 672),34%(n = 336)前哨淋巴结阳性并接受了进一步腋窝手术。其中,45%(n = 152/336)有宏转移,40%(n = 136/336)有微转移,15%(48/336)结果为阳性但受抑制。各前哨淋巴结阳性组患者的人口统计学特征和肿瘤特征无差异。在有微转移的患者中,15%(20/136)有更多阳性非前哨淋巴结,另有6%(8/136)有超过4个总体阳性淋巴结(前哨淋巴结 + 非前哨淋巴结),因此需要辅助性锁骨上/胸壁放疗(p < 0.05)。25%的淋巴结阳性患者有更多非前哨淋巴结转移(85/336),在这些患者中,阳性前哨淋巴结/切除前哨淋巴结的比例(+前哨淋巴结/前哨淋巴结)恒定为1:1。这表明如果所有切除的淋巴结均为阳性,则出现更多阳性非前哨淋巴结的可能性。这种线性趋势在微转移和宏转移中均存在,因此与非前哨淋巴结转移的大小和数量相关。
我们的研究基于前哨淋巴结的分子分析反映了非前哨淋巴结的肿瘤负荷。OSNA有潜力准确识别腋窝微转移。微转移很重要,因为一些有微转移的患者有4个总体阳性淋巴结[前哨淋巴结 + 非前哨淋巴结](在无其他不良临床病理特征时为放疗标准)。此外,我们的研究突出了某些预测非前哨淋巴结转移的因素,有待进一步前瞻性长期数据验证。这将有助于准确计算腋窝肿瘤负荷,尤其是对于有微转移的患者。