Characteristics of Suspicious Breast Lesions Visible Only on MR Imaging: Is It Possible to Classify into Immediate Biopsy and Careful Observation Groups?

PURPOSE: To investigate the characteristics of suspicious MRI-only visible lesions and to explore the validity of subcategorizing these lesions into the following two groups: lesions that would require immediate biopsy (4Bi) and lesions for which careful clinical follow-up could be recommended (4Fo). METHODS: A retrospective review of 108 MRI-only visible lesions in 106 patients who were diagnosed as Breast Imaging Reporting and Data System (BI-RADS) category 4 between June 2018 and June 2022 at our institution was performed by two radiologists. The breast MR images were evaluated according to BI-RADS and additional MRI descriptors (linear ductal, branching, and apparent diffusion coefficient values). The lesions were categorized by previously reported classification systems, and the positive predictive values (PPVs) for the different categories were determined and compared. Subsequently, a new classification system was developed in this study. RESULTS: The total malignancy rate was 31% (34/108). No significant differences between benign and malignant lesions were identified for focus and mass lesions. For non-mass lesions, linear ductal and heterogeneous internal enhancement suggested a benign lesion (P = 0.0013 and P = 0.023, respectively), and branching internal enhancement suggested malignancy (P = 0.0066). Segmental distribution suggested malignancy (P = 0.0097). However, the PPV of segmental distribution with heterogeneous enhancement was significantly lower than that of category 4 segmental lesions with other enhancement patterns (11% vs. 59%; P = 0.0198).As a new classification, the distribution of focal, linear, and segmental was given a score of 0, 1, or 2, and the internal enhancement of heterogeneous, linear-ductal, clumped, branching, and clustered-ring enhancement was given a score of 0, 1, 2, 3, and 4, respectively. When categorized using a scoring system, a statistically significant difference in PPV was observed between 4Fo (n = 27) and 4Bi (n = 33) (7% vs. 61%, P = 0.000029). CONCLUSION: The new classification system was found to be highly capable of subcategorizing BI-RADS category 4 MRI-only visible non-mass lesions into 4Fo and 4Bi.

Examining the effectiveness of a deep learning-based computer-aided breast cancer detection system for breast ultrasound.

PURPOSE: This study aimed to evaluate the clinical usefulness of a deep learning-based computer-aided detection (CADe) system for breast ultrasound. METHODS: The set of 88 training images was expanded to 14,000 positive images and 50,000 negative images. The CADe system was trained to detect lesions in real- time using deep learning with an improved model of YOLOv3-tiny. Eighteen readers evaluated 52 test image sets with and without CADe. Jackknife alternative free-response receiver operating characteristic analysis was used to estimate the effectiveness of this system in improving lesion detection. RESULT: The area under the curve (AUC) for image sets was 0.7726 with CADe and 0.6304 without CADe, with a 0.1422 difference, indicating that with CADe was significantly higher than that without CADe (p < 0.0001). The sensitivity per case was higher with CADe (95.4%) than without CADe (83.7%). The specificity of suspected breast cancer cases with CADe (86.6%) was higher than that without CADe (65.7%). The number of false positives per case (FPC) was lower with CADe (0.22) than without CADe (0.43). CONCLUSION: The use of a deep learning-based CADe system for breast ultrasound by readers significantly improved their reading ability. This system is expected to contribute to highly accurate breast cancer screening and diagnosis.

Risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer: a single-institution 10-year experience.

BACKGROUND: For women diagnosed with hereditary breast and ovarian cancer, the clinical guidelines recommend risk-reducing salpingo-oophorectomy at age 35-40 years or after completion of childbearing. However, there is limited information regarding the current status of risk-reducing salpingo-oophorectomy in Japan. METHODS: To clarify factors influencing decision-making for risk-reducing salpingo-oophorectomy among Japanese women diagnosed with hereditary breast and ovarian cancer and their clinical outcomes, we analyzed the medical records of 157 Japanese women with germline BRCA pathogenic variants (BRCA1 n = 85, BRCA2 n = 71 and both n = 1) at our institution during 2011-21. Specimens obtained from risk-reducing salpingo-oophorectomy were histologically examined according to the sectioning and extensively examining the fimbriated end protocol. RESULTS: The risk-reducing salpingo-oophorectomy uptake rate was 42.7% (67/157). The median age at risk-reducing salpingo-oophorectomy was 47 years. Older age, married state and parity were significantly associated with risk-reducing salpingo-oophorectomy (P < 0.001, P = 0.002 and P = 0.04, respectively). History of breast cancer or family history of ovarian cancer did not reach statistical significance (P = 0.18 and P = 0.14, respectively). Multivariate analyses revealed that older age (≥45 years) and married state may be independent factors associated with risk-reducing salpingo-oophorectomy. Interestingly, the annual number of risk-reducing salpingo-oophorectomy peaked in 2016-17 and has increased again since 2020. The rate of occult cancers at risk-reducing salpingo-oophorectomy was 4.5% (3/67): ovarian cancer (n = 2) and serous tubal intraepithelial carcinoma (n = 1). CONCLUSION: Age and marital status significantly affected decision-making for risk-reducing salpingo-oophorectomy. This is the first study to suggest possible effects of Angelina Jolie's risk-reducing salpingo-oophorectomy in 2015 and the National Health Insurance introduced for risk-reducing salpingo-oophorectomy in 2020. The presence of occult cancers at risk-reducing salpingo-oophorectomy supports clinical guidelines recommending risk-reducing salpingo-oophorectomy at younger ages.

Diagnostic performance of dedicated breast positron emission tomography.

BACKGROUND: Dedicated breast positron emission tomography (dbPET) has been developed for detecting smaller breast cancer. We investigated the diagnostic performance of dbPET in patients with known breast cancer. METHODS: Eighty-two preoperative patients with breast cancer were included in the study (84 tumours: 11 ductal carcinomas in situ [DCIS], 73 invasive cancers). They underwent mammography (MMG), ultrasonography (US), and contrast-enhanced breast magnetic resonance imaging (MRI) before whole-body PET/MRI (WBPET/MRI) and dbPET. We evaluated the sensitivity of all modalities, and the association between the maximum standard uptake value (SUVmax) level and histopathological features. RESULTS: The sensitivities of MMG, US, MRI, WBPET/MRI and dbPET for all tumours were 81.2% (65/80), 98.8% (83/84), 98.6% (73/74), 86.9% (73/84), and 89.2% (75/84), respectively. For 11 DCIS and 22 small invasive cancers (≤ 2 cm), the sensitivity of dbPET (84.9%) tended to be higher than that of WBPET/MRI (69.7%) (p = 0.095). Seven tumours were detected by dbPET only, but not by WBPET/MRI. Five tumours were detected by only WBPET/MRI because of the blind area of dbPET detector, requiring a wider field of view. After making the mat of dbPET detector thinner, all 22 scanned tumours were depicted. The higher SUVmax of dbPET was significantly related to the negative oestrogen receptor status, higher nuclear grade, and higher Ki67 (p < 0.001). CONCLUSIONS: The sensitivity of dbPET for early breast cancer was higher than that of WBPET/MRI. High SUVmax was related to aggressive features of tumours. Moreover, dbPET can be used for the diagnosis and oncological evaluation of breast cancer.

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.

Identifying ductal carcinoma in situ cases not requiring surgery to exclude postoperative upgrade to invasive ductal carcinoma.

BACKGROUND: Prospective cohort studies are being conducted worldwide to identify a low-grade group of ductal carcinoma in situ (DCIS) that does not require surgery. However, to do this, it is necessary to predict which cases, diagnosed with preoperative DCIS, will be upgraded to invasive ductal carcinoma (IDC) after surgery. METHODS: In this study, we evaluated the frequency of IDC upgrades in patients who were preoperatively diagnosed with DCIS at Showa University using the criteria of ongoing clinical trials. We divided our cases into those that could be enrolled in the ongoing trial and those that could not. Moreover, we evaluated whether CNB, which is allowed only in Japanese clinical trials, is related to the IDC mixture. RESULTS: There were 211 (52.1%) cases that matched the criteria of the U.K. and Netherlands trials, of which 62 (29.4%) were upgraded to IDC. A total of 113 (27.9%) cases met the criteria for clinical trials in Japan and the U.S., 25 (22.1%) of which were upgraded to IDC and 47 (34.6%) which matched when considering biopsy methods. The number of cases upgraded to IDC decreased to four (8.5%). CONCLUSIONS: This study demonstrated that there were a certain number of mixed IDC. We will pay attention to the results of ongoing clinical trials regarding how the presence of this mixed IDC affects the prognosis in non-surgery cases. Careful follow-up is recommended for non-surgical treatment.

Optimal Breast Density Characterization Using a Three-Dimensional Automated Breast Densitometry System.

Dense breasts are a risk factor for breast cancer. Assessment of breast density is important and radiologist-dependent. We objectively measured mammographic density using the three-dimensional automatic mammographic density measurement device Volpara™ and examined the criteria for combined use of ultrasonography (US). Of 1227 patients who underwent primary breast cancer surgery between January 2019 and April 2021 at our hospital, 441 were included. A case series study was conducted based on patient age, diagnostic accuracy, effects of mammography (MMG) combined with US, size of invasion, and calcifications. The mean density of both breasts according to the Volpara Density Grade (VDG) was 0-3.4% in 2 patients, 3.5-7.4% in 55 patients, 7.5-15.4% in 173 patients, and ≥15.5% in 211 patients. Breast density tended to be higher in younger patients. Diagnostic accuracy of MMG tended to decrease with increasing breast density. US detection rates were not associated with VDG on MMG and were favorable at all densities. The risk of a non-detected result was high in patients without malignant suspicious calcifications. Supplementary use of US for patients without suspicious calcifications on MMG and high breast density, particularly ≥25.5%, could improve the breast cancer detection rate.

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.

BRCAness as a prognostic indicator in patients with early breast cancer.

BRCAness is defined as a phenotypic copy of germline BRCA mutations, which describes presence of homologous recombination defects in sporadic cancers. We detected BRCAness by multiplex ligation-dependent probe amplification (MLPA) and explored whether BRCAness can be used as a predictor of prognosis. BRCAness status was classified for total 121 breast cancer patients. Forty-eight patients (39.7%) were identified as BRCAness positive. Tumors of BRCAness were more likely to be hormone receptors negative (95.8% vs. 50.7%, P < 0.001), nuclear grade III (76.1% vs. 48.4%, P = 0.001) and triple-negative breast cancer subtype (91.6% vs. 42.5%, P < 0.001). Five-year disease free survival (DFS) (54.0% vs. 88.0%, P < 0.001) and overall survival (OS) (76.3% vs. 93.1%, P = 0.002) were significantly lower in BRCAness patients. In neoadjuvant chemotherapy subgroup analysis, clinical response rate for taxane-based regimen was significantly lower in BRCAness patients (58.3% vs. 77.8%, P = 0.041). Cox regression multivariate analysis showed that BRCAness was the independent prognostic factor for DFS (HR 2.962, 95%CI 1.184-7.412, P = 0.020), but not for OS (HR 2.681, 95%CI 0.618-11.630, P = 0.188). BRCAness is associated with specific characteristics and may suggest resistance to taxane-based chemotherapy. BRCAness can be used as a negative prognostic indicator for breast cancer.

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.

Magnetically Promoted Rapid Immunofluorescence Staining for Frozen Tissue Sections.

Current immunohistochemistry methods for diagnosing abnormal cells, such as cancer cells, require multiple steps and can be relatively slow compared with intraoperative frozen hematoxylin and eosin staining, and are therefore rarely used for intraoperative examination. Thus, there is a need for novel rapid detection methods. We previously demonstrated that functionalized fluorescent ferrite beads (FF beads) magnetically promoted rapid immunoreactions. The aim of this study was to improve the magnetically promoted rapid immunoreaction method using antibody-coated FF beads and a magnet subjected to a magnetic field. Using frozen sections of xenograft samples of A431 human epidermoid cancer cells that express high levels of epidermal growth factor receptor (EGFR) and anti-EGFR antibody-coated FF beads, we reduced the magnetically promoted immunohistochemistry procedure to a 1-min reaction and 1-min wash. We also determined the optimum magnetic force for the antibody reaction (from 7.79 × 10-15 N to 3.35 × 10-15 N) and washing (4.78 × 10-16 N), which are important steps in this technique. Furthermore, we stained paraffin-embedded tissue arrays and frozen sections of metastatic breast cancer lymph nodes with anti-pan-cytokeratin antibody-coated FF beads to validate the utility of this system in clinical specimens. Under optimal conditions, this ultra-rapid immunostaining method may provide an ancillary method for pathological diagnosis during surgery. (J Histochem Cytochem 58:XXX-XXX, 2010).

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.