Kimihito Fujii

Fusion of MRI and Sonography Image for Breast Cancer Evaluation Using Real-time Virtual Sonography with Magnetic Navigation: First Experience

OBJECTIVE We recently developed a real-time virtual sonography (RVS) system that enables simultaneous display of both sonography and magnetic resonance imaging (MRI) cutaway images of the same site in real time. The aim of this study was to evaluate the role of RVS in the management of enhancing lesions visualized with MRI. METHODS Between June 2006 and April 2007, 65 patients underwent MRI for staging of known breast cancer at our hospital. All patients were examined using mammography, sonography, MRI and RVS before surgical resection. Results were correlated with histopathologic findings. MRI was obtained on a 1.5 T imager, with the patient in the supine position using a flexible body surface coil. Detection rate was determined for index tumors and incidental enhancing lesions (IELs), with or without RVS. RESULTS Overall sensitivity for detecting index tumors was 85% (55/65) for mammography, 91% (59/65) for sonography, 97% (63/65) for MRI and 98% (64/65) for RVS. Notably, in one instance in which the cancer was not seen on MRI, RVS detected it with the supplementation of sonography. IELs were found in 26% (17/65) of the patients. Of 23 IELs that were detected by MRI, 30% (7/23) of IELs could be identified on repeated sonography alone, but 83% (19/23) of them were identified using the RVS system (P = 0.001). The RVS system was able to correctly project enhanced MRI information onto a body surface, as we checked sonography form images. CONCLUSIONS Our results suggest that the RVS system can identify enhancing breast lesions with excellent accuracy.

Real-Time Virtual Sonography, A Coordinated Sonography and MRI System that Uses Magnetic Navigation, Improves the Sonographic Identification of Enhancing Lesions on Breast MRI

This study verified that recently developed real-time virtual sonography (RVS) to coordinate a sonography image and the magnetic resonance imaging (MRI) multiplanar reconstruction (MPR) with magnetic navigation was useful. The purpose of this study was to evaluate the accuracy of RVS to sonographically identify enhancing lesions by breast MRI. Between December 2008 and May 2009, RVS was performed in 51 consecutive patients with 63 enhancing lesions. MRI was performed with the patients in the supine position using a 1.5-T imager with a body surface coil to achieve the same position as with sonography. To assess the accuracy of the RVS, the following three issues were analyzed: (i) The sonographic detection rate of enhancing lesions, (ii) the comparison of the tumor size measured by sonography and the MRI-MPR and (iii) the positioning errors as the distance from the actual sonographic position to the expected MRI position in 3-D. Among the 63 enhancing lesions, 42 (67%) lesions were identified by conventional B-mode, whereas the remaining 21 (33%) initial conventional B-mode occult lesions were identified by RVS alone. The sonographic size of the lesions detected by RVS alone was significantly smaller than that of lesions detected by conventional B-mode (p < 0.001). The mean tumor size provided by RVS was 12.3 mm for real-time sonography and 14.1 mm for MRI-MPR (r = 0.848, p < 0.001). The mean positioning errors for the transverse and sagittal planes and the depth from the skin were 7.7, 6.9 and 2.8 mm, respectively. The overall mean 3D positioning error was 12.0 mm. Our results suggest that RVS has good targeting accuracy to directly compare a sonographic image with MRI results without operator dependence.

Solitary esophageal metastasis of breast cancer with 15 years' latency: a case report and review of the literature.

A 68‐year‐old woman with a history of breast and colon cancer at the ages of 48 and 65 years, respectively, who presented with dysphagia is described. An upper gastrointestinal series and endoscopic examination revealed a circumferential stricture without ulceration in the middle‐third area of the esophagus. Computed tomography demonstrated a submucosal tumor in the esophageal wall. A biopsy specimen obtained from the mucosa overlying the tumor revealed poorly differentiated adenocarcinoma, suggesting metastasis from the previous breast cancer. Subtotal esophagectomy with reconstruction was performed. Macroscopically, a submucosal tumor measuring 2.0×1.7 cm was observed in the resected esophagus. Microscopic examination revealed poorly differentiated adenocarcinoma, which was quite similar histologically to the breast cancer resected 15 years previously. Enzyme Immunoassay and Immunohistochemical analyses of the resected tumor revealed positivity for both estrogen and progesterone receptor, confirming the diagnosis of a metastatic cancer from the previous breast tumor.

Reproducible Surveillance Breast Ultrasound Using an Image Fusion Technique in a Short-Interval Follow-up for BI-RADS 3 Lesions: A Pilot Study

The aim of our study was to verify the utility of surveillance ultrasound (US) using real-time virtual sonography (RVS)--to coordinate present US images with past US images reconstructed from previously acquired US volume data using an image fusion technique--for short-interval follow-up of Breast Imaging-Reporting and Data System (BI-RADS) category 3 mass lesions. We enrolled 20 women (23 lesions) with more than 24 mo of follow-up after classification as BI-RADS category 3 during initial US. US surveillance was scheduled at 6, 12 and 24 mo. Measurement of the target lesion diameter was performed after the probe was adjusted to include the maximum diameter of a past US image at each visit. RVS was technically successful in 100% of patients. All target lesions were detected, including two iso-echoic lesions. The mean target lesion diameters at baseline and at 6, 12 and 24 mo were 8.2 ± 4.2, 8.4 ± 4.5, 8.1 ± 4.5 and 8.3 ± 5.0 mm, respectively (p = 0.785). Our results suggest that RVS is a reproducible, operator-independent technique for comparison of US images of BI-RADS category 3 mass lesions obtained at different time points.

A Case of Estrogen Receptor Positive Secretory Carcinoma in a 9-Year-old Girl With ETV6–NTRK3 Fusion Gene

The patient was a 9-year-old premenarcheal pediatric female, whose chief complaint was a well-circumscribed palpable right breast mass without nipple discharge. Although the patient had noticed the lump 2 years prior to hospital admission, its size (1.5 × 1.3 cm) had been stable. There was no family history or previous history of malignancies. Physical examination showed a well-delimited, elastic-firm and movable tumor just beneath the nipple and areolar complex. Regional lymph nodes were not palpable. Ultrasonography and breast computed tomography revealed a subareolar oval-shaped tumor exhibiting homogeneous echogenicity with clear margins. Distant metastases could not be detected using whole-body computed tomographic scans. A fine-needle aspiration cytology specimen showed atypical cells with prominent nucleoli and abundant intracellular secretory material, suggesting the possibility of secretory carcinoma. Histopathological analysis of the core needle biopsy specimen revealed that the tumor was a secretory carcinoma. The patient underwent total mastectomy with sentinel lymph node biopsy. Metastases were not observed in the removed lymph nodes. Estrogen receptor was weakly positive and progesterone receptor was negative. Human epidermal growth factor receptor 2 expression was also negative. In addition, the ETV6 (exon 5) and NTRK3 (exon 13) fusion gene was detected using the reverse transcription-polymerase chain reaction method. This gene is considered specific for secretory carcinoma. Immunohistochemistry revealed weak basal differentiation [cytokeratin 5/6(CK5/6)(+), vimentin(+) and epidermal growth factor receptor(+)]. The patient has received no adjuvant therapy and is currently disease free at 12 months after surgery.

Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions

In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status, occasionally changes. This change, in addition to the Ki67 index were evaluated at sites of recurrence and the correlation between changes in tumor phenotype and survival were assessed in breast cancer patients. Comparisons in pathological parameters between primary and metastatic lesions were drawn between ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The association between changes in tumor phenotype and patient survival was assessed. The hormone receptor status changed from positive, in the primary lesions, to negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients, respectively. Conversion from negative to positive status was confirmed in 27.2% (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from negative (primary lesion) to positive (metastatic lesion) occurred in seven patients (10%). The mean Ki67 index of primary lesions with positive hormone receptor status was significantly lower than at sites of recurrence with any hormone receptor status, from 10.9±9.8 standard deviation (SD) to 22.9±18.6 (P=0.031) and 12.2±10.5 SD to 27.4±20.9 (P=0.023), for ER and PR, respectively. The mean overall survival of patients with ER status conversion from positive to negative was 7.4±1.2 standard error (SE) years, and 14.8±1.4 SE years for patients who retained positive ER status (P=0.005, log-rank), with a hazard ratio of 3.44 (95% confidence interval, 1.36-8.33). This difference in survival based upon change in ER status was similarly observed in patients with PR status conversion in the same direction. Thus, ER and PR status conversion at the time of recurrence strongly impact survival, particularly if the change is from positive (primary lesion) to negative (metastatic lesion). Monitoring the biological behavior of breast cancer may benefit a patient by allowing for a novel personalized treatment strategy.

The role of real-time virtual sonography in the management of enhancing breast lesions on contrast-enhanced MRI.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #4001 [Purpose] The aim of this study was to evaluate the role of real-time virtual sonography (RVS) in the management of enhancing breast lesions visualized with contrast-enhanced MRI. [Materials] Between April 2006 and May 2008, 92 women underwent breast MRI at our hospital. Of these 92 patients, 55 underwent MRI for staging of known breast cancer, and the remaining 37 underwent MRI for problem solving, including abnormal findings at physical examination or on conventional images. All patients were examined using mammography, sonography, MRI and RVS. The RVS system is capable of superimposing a sonography image with the MRI image of the same section in real time using a position tracking system with a magnetic sensor. Breast MR images were obtained on a 1.5-T imager using a flexible body surface coil, with the patient in the supine position. [Results] Overall sensitivity for detecting primary breast cancer was 74% (43/58) for mammography, 93% (54/58) for sonography, 97% (56/58) for MRI, and 97% (56/58) for RVS. Incidental enhancing / suspicious lesions (IELs) which were not predicted by the previous conventional imaging techniques were found in 55% of the patients (51/92),. Of these, 59% (24/41) of IELs could be identified only on repeated sonography, but 85% (35/41) of them were identified easily using the RVS system (p<0.05). The RVS system was able to project enhanced MRI information onto a body surface correctly while checking sonography form images without the use of large-scale equipment. Histologically, 10% (4/41) of the IELs were invasive ductal carcinoma. [Conclusions] The present results suggest that the RVS system offers excellent accuracy for identification of enhancing breast lesions. RVS can accurately select the cases in which MR guided biopsies are required. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4001.

Pre-Operative Planning Using Real-Time Virtual Sonography, an MRI/Ultrasound Image Fusion Technique, for Breast-Conserving Surgery in Patients with Non-Mass Enhancement on Breast MRI: A Preliminary Study

The purpose of this retrospective study was to evaluate the effect of pre-operative planning using real-time virtual sonography (RVS), a magnetic resonance imaging (MRI)/ultrasound (US) image fusion technique on breast-conserving surgery (BCS) in patients with non-mass enhancement (NME) on breast MRI. Between 2011 and 2015, we enrolled 12 consecutive patients who had lesions with NME that exceeded the US hypo-echoic area, in which it was particularly difficult to evaluate the tumor margin. During pre-operative planning before breast-conserving surgery, RVS was used to delineate the enhancing area on the breast surface after additional supine breast MRI was performed. We analyzed both the surgical margin positivity rate and the re-operation rate. All NME lesions corresponded to the index cancer. In all patients, the diameter of the NME lesion was greater than that of the hypo-echoic lesion. The median diameters of the NME and hypo-echoic lesions were 24 mm (range: 12-39 mm) and 8.0 mm (range: 4.9-18 mm), respectively (p = 0.0002). After RVS-derived skin marking was performed on the surface of the affected breast, lumpectomy and quadrantectomy were conducted in 7 and 5 patients, respectively. The surgical margins were negative in 10 (83%) patients. Two patients with positive margins were found to have ductal carcinoma in situ in 1 duct each, 2.4 and 3.2 mm from the resection margin, respectively. None of the patients required additional resection. Although further prospective studies are required, the findings of our preliminary study suggest that it is very well possible that the use of RVS-derived skin marking during pre-operative planning for BCS in patients with NME would have resulted in surgical outcomes similar to or better than those obtained without the use of such marking.

Abstract P4-02-13: Breast ultrasound surveillance with image fusion technique in a short-interval follow-up for BI-RADS category 3 mass lesions

PURPOSE: Breast ultrasound (US) is a diagnostic imaging modality that is now widely used as an adjunct to mammography for evaluation of breast abnormalities. In the Breast Imaging-Reporting and Data System (BI-RADS) lexicon, a solid mass with an oval shape, well-circumscribed margins and parallel orientation is classified as category 3 (BI-RADS category 3 mass lesions) . This mass should have a risk of malignancy of METHOD AND MATERIALS: We enrolled 20 women (23 lesions) with more than 24 months of follow-up after classification as BI-RADS category 3 during initial US. US surveillance was scheduled at 6, 12 and 24 months. Three-dimensional assessment of morphologic features was performed while serially checking past US volume data corresponding to the present US probe position. Measurement of the target lesion diameter was performed after the probe was adjusted to include the maximum diameter of a past US image at each visit. RESULTS: RVS was technically successful in 100% of patients. All target lesions were detected, including two iso-echoic lesions. The mean target lesion diameters at baseline and at 6, 12 and 24 months were 8.2+4.2, 8.4+4.5, 8.1+4.5 and 8.3+5.0 mm, respectively . Statistical analysis using a Friedman test with multiple comparisons revealed no significant difference between the diameters at each time point (p = 0.785). RVS was used to directly compare the US morphologic characteristics and sized of lesions. Furthermore, the RVS data can be reproduced in their entirety for independent review at a later date by using stored US volume data. CONCLUSION:Our results suggest that RVS is reproducible, operator-independent technique for comparison of US images of BI-RADS category 3 mass lesions obtained at different time points. Citation Format: Nakano S, Fujii K, Kousaka J, Mouri Y, Ando T. Breast ultrasound surveillance with image fusion technique in a short-interval follow-up for BI-RADS category 3 mass lesions [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-02-13.

380PCONVERSION OF THE HORMONAL RECEPTORS ON RECURRENT BREAST CANCER PATIENTS

ABSTRACT Aim: When clinicians consider the treatment strategies for the recurrent breast cancer patients, the choice of treament is generally determined with the information of the pathological diagnosis of the primaries. However, the tumor phenotype is sometimes altered when it recurs. In this study, we compared the tumor characteristics among the primaries, metastatic lymph nodes and the recurrences, and assessed the correlation with the survival. Methods: Seventy breast cancer patients whose diagnosis of the primaries and the metastases had been confirmed at Aichi Medical University Hospital were enrolled in this study. The comparative assessment of the lesions was performed on the following factors; the status of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 index. Association with those factors were assessed and the survival was etimated. Results: For ER, 19.8% of patients with the positive status in the primaries changed to the negative in the metastases (ER + /-) and the reverse conversion (from negative to positve; ER-/+) were confimed in 27.2% patients. In the similar fashion, PR + /- was recognized in 39.5% and PR-/+ in 31.2%. As for the metastatic lymph nodes, only 1 case of ER-positive in the primary converted to the negative, but 18.8% of PR-positive and 35.7% of PR-negative were altered to the each opposite receptor status. Ki-67 index increased significantly when the negative conversion occurred in the cases of the positive primaries. The overall survival was worsened significantly on the patients with negative alteration from the positive primaries. The hazard ratio for the survival was 0.29 (95% CI = 0.12-0.73) in the cases of ER + /+ vs. ER + /-, and 0.12 (95%CI = 0.03-0.43) in the cases of PR + /+ vs. PR + /-. Conclusions: The receptor conversion that occur concomitantly with the recurrence of the breast cancer, was observed in about 20 to 40% recurrent cases. On metastasizing, the breast cancer acquired more aggressive nature, especially when its receptor status was altered from positive to negative. The tumor characteristics such as receptor status can be changed so easily that the treatment strategy have to be reconsidered for making an appropriate judgement on the next therapeutic way. Disclosure: All authors have declared no conflicts of interest.