Sentinel Node Biopsy for Breast Cancer : Aspects and evolution

Abstract: Sentinel Node Biopsy (SNB) in clinical practice was pivotal to the shaping of modern diagnosis, staging and treatment of patients with breast cancer. The use of radioisotope (RI) and blue dye (BD) has led to high detection rates with low false negatives, but delivery-of-care limitations connected to these tracers as well as the need for methods addressing new clinical conundrums delineates the urge for new tracers with comparable performance, easier logistics and, ideally expanded implementations. Aim of the present thesis is to examine the outcomes of Superparamagnetic Iron Oxide (SPIO) nanoparticles, a new tracer based on magnetism for the detection of the sentinel nodes.Paper I is a prospective multicentre trial comparing SPIO to RI+BD, with all tracers injected at the same patient. In 206 patients, SPIO had a similar detection rate (97.6 vs 97.1%, p=0.76) whereas concordance between methods was 98%. The study was completed by a meta-analysis of similar trials published until that point. The detection rates were comparable (fixed OR:1.10; 0.67,1.79, p=0.71), and so was concordance between tracers (fixed RD: 0.00; -0.01, 0.01, p=0.82). Discoloration was present after periareolar SPIO injection in 39% of patients, almost exclusively treated with breast conservation, which reduced to 8.6% after 15 months of follow-up.Paper II was a pilot study of twelve patients with breast cancer and SNB performed where SPIO and the combination of RI+BD were injected, but SPIO was injected up to 15 days preoperatively, with total success in detection and complete concordance.Paper III tested the performance of SPIO as a sole tracer in a pragmatic double-arm non-randomised trial comparing it to the combination of RI+BD. Detection was 95.7% for SPIO and 96.8% for RI (p = 0.59). The preoperative injection of SPIO (1-27 d) enhanced SPIO specific detection (95.7 vs 86%, p=0.002).Paper IV is an interim analysis of a multicentre cohort study including patients with high-risk DCIS planned for breast conservation or any DCIS planned for mastectomy. SPIO was injected to “mark” the sentinel node but SNB was performed in a second operation only if invasive cancer was found at the first operation. In 151 included patients, this technique led to avoidance of 81.5% SNB, with a cost reduction of 14.1% for the entire cohort and 25.8% for the patients that did not have invasive cancer. The detection rate at reoperation was superior for SPIO and comparable with SNB detection at primary operation.In conclusion, SPIO is a novel tracer for SNB in breast cancer with comparable performance, fit for performance in a global setting and with wider clinical implementations compared to RI+BD.