Exploratory Study of Superparamagnetic Iron Oxide Dose Optimization in Breast Cancer Sentinel Lymph Node Identification Using a Handheld Magnetic Probe and Iron Quantitation.

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.

Magnetically Guided Localization Using a Guiding-Marker System® and a Handheld Magnetic Probe for Nonpalpable Breast Lesions: A Multicenter Feasibility Study in Japan.

Accurate pre-operative localization of nonpalpable lesions plays a pivotal role in guiding breast-conserving surgery (BCS). In this multicenter feasibility study, nonpalpable breast lesions were localized using a handheld magnetic probe (TAKUMI) and a magnetic marker (Guiding-Marker System®). The magnetic marker was preoperatively placed within the target lesion under ultrasound or stereo-guidance. Additionally, a dye was injected subcutaneously to indicate the extent of the tumor excision. Surgeons checked for the marker within the lesion using a magnetic probe. The magnetic probe could detect the guiding marker and accurately localize the target lesion intraoperatively. All patients with breast cancer underwent wide excision with a safety margin of ≥5 mm. The presence of the guiding-marker within the resected specimen was the primary outcome and the pathological margin status and re-excision rate were the secondary outcomes. Eighty-seven patients with nonpalpable lesions who underwent BCS, from January to March of 2019 and from January to July of 2020, were recruited. The magnetic marker was detected in all resected specimens. The surgical margin was positive only in 5/82 (6.1%) patients; these patients underwent re-excision. This feasibility study demonstrated that the magnetic guiding localization system is useful for the detection and excision of nonpalpable breast lesions.

Multicenter clinical trial on sentinel lymph node biopsy using superparamagnetic iron oxide nanoparticles and a novel handheld magnetic probe.

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 (99m Tc) 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.

The Loss of Lymph Node Metastases After Neoadjuvant Chemotherapy in Patients With Cytology-proven Axillary Node-positive Primary Breast Cancer.

BACKGROUND: Axillary lymph node (LN) dissection after neoadjuvant chemotherapy (NAC) still remains a standard treatment of initially LN-positive primary breast cancer because of the difficulty of assessment of LN status. The aim of this study was to assess the LN status after NAC in initially LN-positive primary breast cancer patients who were assessed as clinically LN-negative after NAC (ycN0) and identify factors associated with loss of LN metastasis. PATIENTS AND METHODS: The study cohort comprised 279 patients with cytology-proven LN-positivity before NAC. LN status was assessed by ultrasonography. Regional recurrence-free survival and overall survival according to pathologic LN after NAC (ypN) status were assessed in patients with ycN0. RESULTS: Of the 279 patients, 179 patients (64.2%) had ycN0. High nuclear grade, estrogen receptor-negative (ER-), and human epidermal growth factor receptor 2-positive (HER2+), were significant predictors of ycN0/ypN0 (P < .001, .007, and .046, respectively). Metastases persisted in 1 or 2 LNs for 5 (20.0%) of 25 patients with ER-/HER2+ and for 4 (21.1%) of 19 patients with ER-/HER2-, and in 3 or more LNs for 0 (0%) of 25 patients with ER-/HER2+ and for 1 (5.3%) of 19 patients with ER-/HER2-. Patients with ER+ tumors had more numerous residual LN metastases than those with ER- tumors (P < .001). Among patients with ycN0, ypN status was not associated with regional recurrence-free survival or overall survival. CONCLUSIONS: Three or more residual LN metastases were rare in patients with ER- tumors if assessed as ycN0 by ultrasonography. Prospective studies are needed to confirm the prognostic impact of not performing axillary lymph node dissection in such patients.

Digital volumetric measurement of mammographic density and the risk of overlooking cancer in Japanese women.

BACKGROUND: Breast density often affects cancer detection via mammography (MMG). Because of this, additional tests are recommended for women with dense breasts. This study aimed to reveal trends in breast density among Japanese women and determine whether differences in breast density differentially affected the detection of abnormalities via MMG. METHODS: We retrospectively analyzed 397 control women who underwent MMG screening as well as 269 patients who underwent surgery for breast cancer for whom preoperative MMG data were available. VolparaDensity™ (Volpara), a three-dimensional image analysis software with high reproducibility, was used to calculate breast density. Breasts were categorized according to the volumetric density grade (VDG), a measure of the percentage of dense tissue. The associations between age, VDG, and MMG density categories were analyzed. RESULTS: In the control group, 78% of women had dense breasts, while in the breast cancer group, 87% of patients had dense breasts. One of 36 patients with non-dense breasts (2.7%) was classified as category 1 or 2 (C-1 or C-2), indicating that abnormal findings could not be detected by MMG. The proportion of patients with breast cancer who had dense breasts and were classified as C-1 or C-2 was as high as 22.3%. CONCLUSIONS: The proportions of Japanese women with dense breasts were high. In addition, the false-negative rate for women with dense breasts was also high. Owing to this, Japanese women with dense breasts may need to commonly undergo additional tests to ensure detection of breast cancer in the screening MMG.

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients With an Initial Diagnosis of Cytology-Proven Lymph Node-Positive Breast Cancer.

BACKGROUND: Sentinel lymph node biopsy (SNB) is the standard treatment of node-negative breast cancer; however, whether SNB should be performed for patients with node-positive disease before neoadjuvant chemotherapy (NAC) is controversial. We evaluated the accuracy of SNB after NAC in patients with breast cancer with nodal metastasis before chemotherapy to determine the false-negative rate (FNR) and detection rate for SNB. PATIENTS AND METHODS: In the present multicenter prospective study performed from September 2011 to April 2013, 143 patients with breast cancer and positive axillary nodes, proved by fine needle aspiration cytology at the initial diagnosis (stage T1-T3N1M0), were enrolled. All patients underwent breast surgery with SNB and complete axillary lymph node dissection. RESULTS: After NAC, the pathologic complete nodal response rate was 52.4%. The sentinel lymph node could be identified in 130 cases (90.9%); the FNR was 16.0% (13 of 81). The FNR of each clinical subtype was 42.1% (8 of 19) for the estrogen receptor-positive and human epithelial growth factor 2 (HER2)-negative (luminal type), 16.7% (2 of 12) for ER-positive and HER2-positive (luminal-HER2 type), 3.2% (1 of 31) for HER2-positive (HER2-enriched type), and 10.5% (2 of 19) for ER-negative and HER2-negative (triple-negative breast cancer; P = .003). The FNR was significantly greater in the luminal than in the nonluminal type (odds ratio, 9.91; 95% confidence interval, 6.77-14.52). CONCLUSION: SNB after NAC in patients with initially node-positive breast cancer was technically feasible but should not be recommended for the luminal subtype. However, the tumor subtype can guide patient selection, and axillary lymph node dissection could be omitted for the luminal-HER2, HER2-enriched, and triple-negative breast cancer subtypes.

BRCAness predicts resistance to taxane-containing regimens in triple negative breast cancer during neoadjuvant chemotherapy.

BACKGROUND: To provide optimal treatment of heterogeneous triple negative breast cancer (TNBC), we need biomarkers that can predict the chemotherapy response. PATIENTS AND METHODS: We retrospectively investigated BRCAness in 73 patients with breast cancer who had been treated with taxane- and/or anthracycline-based neoadjuvant chemotherapy (NAC). Using multiplex, ligation-dependent probe amplification on formalin-fixed core needle biopsy (CNB) specimens before NAC and surgical specimens after NAC. BRCAness status was assessed with the assessor unaware of the clinical information. RESULTS: We obtained 45 CNB and 60 surgical specimens from the 73 patients. Of the 45 CNB specimens, 17 had BRCAness (38.6% of all subtypes). Of the 23 TNBC CNB specimens, 14 had BRCAness (61% of TNBC cases). The clinical response rates were significantly lower for BRCAness than for non-BRCAness tumors, both for all tumors (58.8% vs. 89.3%, P = .03) and for TNBC (50% vs. 100%, P = .02). All tumors that progressed with taxane therapy had BRCAness. Of the patients with TNBC, those with non-BRCAness cancer had pathologic complete responses significantly more often than did those with BRCAness tumors (77.8% vs. 14.3%, P = .007). After NAC, the clinical response rates were significant lower for BRCAness than for non-BRCAness tumors in all subtypes (P = .002) and in TNBC cases (P = .008). After a median follow-up of 26.4 months, 6 patients-all with BRCAness-had developed recurrence. Patients with BRCAness had shorter progression-free survival than did those with non- BRCAness (P = .049). CONCLUSION: Identifying BRCAness can help predict the response to taxane, and changing regimens for BRCAness TNBC might improve patient survival. A larger prospective study is needed to further clarify this issue.

Positron emission mammography (PEM): reviewing standardized semiquantitative method.

PURPOSE: To validate semiquantitative analysis of positron emission mammography (PEM). METHODS: Fifty women with histologically confirmed breast lesions were retrospectively enrolled. Semiquantitative uptake values (4 methods), the maximum PEM uptake value (PUVmax), and the lesion-to-background (LTB) value (3 methods) were measured. LTB is a ratio of the lesion's PUVmax to the mean background; LTB1, LTB2, and LTB3 (which were calculated on different background) were used to designate the three values measured. Interobserver reliability between two readers for PUVmax and the LTBs was tested using the interobserver correlation coefficient (ICC). The likelihood ratio test was used to evaluate the relationship between ICCs. Receiver operating characteristic (ROC) curves were calculated for all methods. Diagnostic accuracy in differentiating benign tissue from malignant tissue was compared between PUVmax and LTB1. RESULTS: The ICC rate was 0.971 [95 % confidence interval (CI) 0.943-0.986] for PUVmax, 0.873 (95 % CI 0.758-0.935) for LTB1, 0.965 (95 % CI 0.925-0.983) for LTB2, and 0.895 (95 % CI 0.799-0.946) for LTB3. However, there were some technical difficulties in the practical use of LTB2 and LTB3. The likelihood ratio test between PUVmax and LTB1 was statistically significant (p < 0.001). ROC curves of the 4 methods had similar characteristics. The median PUVmax was 1.39 for benign lesions and 3.70 for malignant lesions. LTB1 was 1.92 for benign lesions and 4.78 for malignant lesions. Significant differences (p < 0.001) in both PUVmax and LTB1 were observed between groups. CONCLUSION: Due to its simplicity and reproducibility, PUVmax is superior to LTB as an indicator for PEM in semiquantitative analysis.

JSUM ultrasound elastography practice guidelines: breast.

Ten years have passed since the first elastography application: Real-time Tissue Elastography™. Now there are several elastography applications in existence. The Quality Control Research Team of The Japan Association of Breast and Thyroid Sonology (JABTS) and the Breast Elasticity Imaging Terminology and Diagnostic Criteria Subcommittee, Terminology and Diagnostic Criteria Committee of the Japan Society of Ultrasonics in Medicine (JSUM) have advocated breast elastography classifications for exact knowledge and good clinical use. We suggest two types of classifications: the technical classification and the classification for interpretation. The technical classification has been created to use vibration energy and to make images, and also shows how to obtain a good elastic image. The classification for interpretation has been prepared on the basis of interpretation of evidence in this decade. Finally, we describe the character and specificity of each vender equipment. We expect the present guidelines to be useful for many physicians and examiners throughout the world.

Ultrasonography- and/or mammography-guided breast conserving surgery for ductal carcinoma in situ of the breast: experience with 87 lesions.

BACKGROUND: It is very important to excise ductal carcinoma in situ (DCIS) with sufficient margins to prevent local recurrence. We describe the experience of ultrasonography (US)-guided and/or mammography (MMG)-guided breast conserving surgery (BCS) for DCIS. METHODS: In this retrospective study, we considered 87 consecutive lesions of 86 patients treated with US- and/or MMG-guided BCS between January and December 2006. RESULTS: The mean age of the 86 patients was 50.0 years (range 28-80 years). Preoperative mapping was performed using US alone for 49 lesions without microcalcifications and using US and MMG for 38 lesions with microcalcifications. Eighty-one (93.1%) of the 87 lesions were diagnosed as non-comedo type or mixed type, and 6 lesions (6.9%) were diagnosed as comedo type of DCIS. Sixty-five lesions (74.8%) were diagnosed as negative margins, 15 lesions (17.2%) as close margins, and 7 lesions (8.0%) as positive margins. Three lesions (3.4%) without microcalcifications that were mapped using US alone underwent additional resection in a second operation. The maximum tumor size was correlated with margin status (p = 0.043). CONCLUSION: Thus US- and/or MMG-guided BCS is a reliable method for treating patients with DCIS regardless of histopathological type and offers the advantage of being noninvasive and nonstressful for patients.