Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue

Background

Despite recent developments in preoperative breast cancer imaging, intraoperative localization of tumor tissue can be challenging, resulting in tumor-positive resection margins during breast conserving surgery. Based on certain physicochemical similarities between Technetium(^99mTc)-sestamibi (MIBI), an SPECT radiodiagnostic with a sensitivity of 83–90% to detect breast cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue (MB), we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging.

Methods

Twenty-four patients with breast cancer, planned for surgical resection, were included. Patients were divided in 2 administration groups, which differed with respect to the timing of MB administration. N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery. The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department. Results were confirmed by NIR fluorescence microscopy.

Results

20/24 (83%) of breast tumors (carcinoma in N = 21 and ductal carcinoma in situ in N = 3) were identified in the resected specimen using NIR fluorescence imaging. Patients with non-detectable tumors were significantly older. No significant relation to receptor status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4 ± 0.8. There was no significant difference between TBR and background signal between administration groups. In 2/4 patients with positive resection margins, breast cancer tissue identified in the wound bed during surgery would have changed surgical management. Histology confirmed the concordance of fluorescence signal and tumor tissue.

Conclusions

This feasibility study demonstrated an overall breast cancer identification rate using MB of 83%, with real-time intraoperative guidance having the potential to alter patient management.     

乳腺导管原位癌个体化局部治疗的研究进展和前景

乳腺X线片的广泛应用,使乳腺导管原位癌(DCIS)的早期诊断率显著升高。DCIS的局部治疗模式也不断发展,从乳房切除术到乳房保留术续贯全乳放疗,再到大分割放疗及部分乳腺短程照射的应用。虽然全乳放疗疗效明确,但其在低危DCIS的应用价值仍存在争议。DCIS局部治疗的未来研究将集中于建立更精确的局部复发风险分层系统指导个体...     

FISH检测乳腺癌HER-2基因扩增及17号染色体多体状况及其临床病理学意义的分析

目的:总结分析临床应用荧光原位杂交(FISH)技术检测诊断乳腺癌大样本的经验和临床病理学意义。方法:用FISH技术诊断1 699例乳腺浸润性导管癌HER-2基因扩增和17号染色体多体状态,并分析HER-2基因扩增与其他重要生物指标及临床病理的关系。结果:乳腺癌HER-2基因扩增阳性率为52.6%(894/1 699);乳腺癌17号染色体多体阳性率为12.7%(216/1 699)。HER-2基因扩增与HER-2表达状况和17号染色体多体呈正相关,P值分别为0.000 1和0.009;乳腺癌HER-2基因扩增与肿瘤大小(P=0.008)、病理学分级(P=0.025)、淋巴结转移(P=0.015)和Ki-67(P=0.004)呈正相关,与ER(P=0.002)、PR(P=0.001)和Bcl-2(P=0.028)呈负相关。HER-2基因扩增的乳腺癌赫赛汀用药组预后明显优于未用药组(Log-rank=38.5;P=0.000 1);17号染色体多体的乳腺癌赫赛汀用药组患者较未用药组复发率低(P=0.022)。结论:临床应用FISH技术诊断HER-2基因扩增靶标来指导乳腺癌的分子靶向治疗可以明显改善患者的预后,值得进一步推广应用。