Background Sentinel lymph node biopsy is a standard staging procedure for early axillary lymph node‐negative breast cancer. As an alternative to the currently used radioactive tracers for sentinel lymph node (SLN) detection during the surgical procedure, a number of studies have shown promising results using superparamagnetic iron oxide (SPIO) nanoparticles. Here, we developed a new handheld, cordless, and lightweight magnetic probe for SPIO detection. Methods Resovist (SPIO nanoparticles) were detected by the newly developed handheld probe, and the SLN detection rate was compared to that of the standard radioisotope (RI) method using radioactive colloids (99mTc) and a blue dye (indigo carmine). This was a multicenter prospective clinical trial that included 220 patients with breast cancer scheduled for sentinel node biopsy after a clinical diagnosis of negative axillary lymph node from three facilities in Japan. Results Of the 210 patients analyzed, SLN was detected in 94.8% (199/210 cases, 90% confidence interval [CI]) with our magnetic method and in 98.1% (206/210 cases, 90% CI) with the RI method. The magnetic method exceeded the threshold identification rate of 90%. Conclusion This was the first clinical study to use a novel handheld magnetometer to detect SLN, which we demonstrate to be not inferior to the RI method.

This exploratory study compared doses of ferucarbotran, a superparamagnetic iron oxide nanoparticle, in sentinel lymph nodes (SLNs) and quantified the SLN iron load by dose and localization. Eighteen females aged ≥20 years scheduled for an SLN biopsy with node-negative breast cancer were divided into two equal groups and administered either 1 mL or 0.5 mL ferucarbotran. Iron content was evaluated with a handheld magnetometer and quantification device. The average iron content was 42.8 µg (range, 1.3–95.0; 0.15% of the injected dose) and 21.9 µg (1.1–71.0; 0.16%) in the 1-mL and 0.5-mL groups, respectively (p = 0.131). The iron content of the closest SLN compared to the second SLN was 53.0 vs. 10.0 µg (19% of the injected dose) and 34.8 vs. 4.1 µg (11.1%) for the 1-mL and 0.5-mL groups, respectively (p = 0.001 for both). The magnetic field was high in both groups (average 7.30 µT and 6.00 µT in the 1-mL and 0.5-mL groups, respectively) but was not statistically significant (p = 0.918). The magnetic field and iron content were correlated (overall SLNs, p = 0.02; 1-mL, p = 0.014; 0.5-mL, p = 0.010). A 0.5-mL dose was sufficient for SLN identification. Primary and secondary SLNs could be differentiated based on iron content. Handheld magnetometers could be used to assess the SLN iron content.

Background: Non-palpable breast lesions represent about 25-35% of all breast cancers diagnosed in developed countries, according to findings based on the evolution of imaging modalities such as MRI, and the uses reliable biopsy techniques such as ultrasound-guided or stereo-guided vacuum assisted biopsy. Wire -guided localization (WGL), radio-guided localization (RGL), and SAVI SCOUT localization (SSL) have been presented as a surgical procedure for non-palpable breast lesion. The reported disadvantages of WGL are related to mechanical stimulation of wire plucking, kinking, and patient discomfort. RGL has issues regarding radioactive licensing, handling, and waste management, and the SSL system requires high start-up costs. To eliminate these problems, we verified the magnetically guided localization (MGL) method for breast lesion localization by means of the combinations of the magnetic probe TAKUMI (ISO13485, Matrix cell Research Institute Inc., Tokyo, Japan) and the guiding-marker system® (Hakko, Tokyo, JAPAN). The TAKUMI is a novel handheld magnetic probe with a permanent magnet and a Hall magnetic sensor for detecting magnetic substances. It was newly developed at the University of Tokyo under a grant from the Japan Agency for Medical Research and Development (AMED). The aim of this study was to evaluate the feasibility and safety of our MGL system. Method: Patients were enrolled in this multi-center, open-label trial from January 2019 to March 2019 at two University Hospitals. The inclusion criteria were age 20 or older female patients who had non-palpable breast lesions, for which breast-conserving surgery or tumor resection was performed. Patients who had a metal allergy, pregnancy, or inflammatory breast cancer were excluded. The guiding-marker system® consists of a stainless-steel hook (φ 0.28 × 10 mm) connected with a nylon thread and an a 21-gauge 10 cm long steel needle.The marker was inserted into the center of the target lesions using ultrasound guidance or stereo guidance within 4 days before surgery. The TAKUMI was used to determine whether the guiding marker was detectable or not before, during, and after the surgical resection of the specimen. The resection rate of the guiding marker, surgical margin status, and re-operation rates were evaluated as the primary outcomes, and the volume and weight of the excised specimen were evaluated as secondary outcomes. The study protocol of the evaluation of magnetic probe system for detecting of non-palpable lesions of the breast was approved by the Institutional Review Board of Nippon Medical School Foundation (CRB3180001) and was registered at https://jrct.niph.go.jp/re (protocol record jRCTs032180422). Written informed consent was obtained from all participants. Results: Forty-one patients were recruited into this study. Thirty-eight patients (92.6%) underwent breast-conserving surgery for breast cancer treatment, and 3 (7.3%) underwent tumor resection for biopsy purposes. All guiding markers were resected during the initial surgical operation. Three out of 38 breast cancer patients (7.9%) were diagnosed as margin positive in frozen section analysis; 2 (5.2%) underwent additional resection during the initial surgery due to the positive margin, and 1 (2.6%) underwent subsequent surgery due to the positive margin on final pathology. Eight patients (21%) underwent boost radiation therapy due to the close margin (<5mm). The median excised specimen weight was 28 g. The range was wide (2-131 g) and depended on the expanse of the lesion. No complications or adverse events were recorded in relation to either the marker placement or the surgery. Conclusion: These data clearly show that MGL is a reliable, accurate, and convenient localization system for non-palpable breast lesions. It is able to eliminate the disadvantages of WGL, RGL, and SSL. Citation Format: Tomoko Kurita, Kanae Taruno, Seigo Nakamura, Hiroyuki Takei, Katsutoshi Enokido, Takashi Kuwayama, Yoko Kanada, Sadako Akashi, Maki Nakai, Meishi Hankyo, Keiko Yanagihara, Takashi Sakatani, Kentaro Sakamaki, Akihiko Kuwahata, Masaki Sekino, Moriaki Kusakabe. Magnetic guided localization for non-palpable breast lesion: A multi-center open-label trial in Japan [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-17.