Mijung Jang

Trastuzumab-Conjugated Liposome-Coated Fluorescent Magnetic Nanoparticles to Target Breast Cancer

Objective To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNP@m-SiO2]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNP@m-SiO2]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer. Materials and Methods The physiochemical characteristics of Lipo[MNP@m-SiO2] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNP@m-SiO2] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin®)-conjugated Lipo[MNP@m-SiO2] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging. Results We obtained uniformly-sized and evenly distributed Lipo[MNP@m-SiO2] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNP@m-SiO2] was observed by in vitro fluorescence and MR imaging. Conclusion Trastuzumab-conjugated Lipo[MNP@m-SiO2] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.

Distinguishing Benign from Malignant Masses at Breast US: Combined US Elastography and Color Doppler US—Influence on Radiologist Accuracy

PURPOSE To investigate the effect of the combined use of ultrasonographic (US) elastography and color Doppler US on the accuracy of radiologists in distinguishing benign from malignant nonpalpable breast masses and in making the decision for biopsy recommendations at B-mode US. MATERIALS AND METHODS This prospective study was conducted with institutional review board approval; written informed consent was obtained. A cohort of 367 biopsy-proved cases in 319 women (age range, 22-78 years; mean age, 48.6 years) with B-mode US, US elastographic, and Doppler US images was included. Five blinded readers independently scored the likelihood of malignancy for four data sets (ie, B-mode US alone, B-mode US and elastography, B-mode US and Doppler US, and B-mode US, US elastography, and Doppler US). The area under the receiver operating characteristic curve (A(z)) values, sensitivities, and specificities of each data set were compared. RESULTS The A(z) of B-mode US, US elastography, and Doppler US (average, 0.844; range, 0.797-0.876) was greater than that of B-mode US alone (average, 0.771; range, 0.738-0.798) for all readers (P = .001 for readers 1, 2, and 3; P < .001 for reader 4; P = .002 for reader 5). When both elastography and Doppler scores were negative, leading to strict downgrading, the specificity increased for all readers from an average of 25.3% (75.4 of 298; range, 6.4%-40.9%) to 34.0% (101.2 of 298; range, 26.5%-48.7%) (P < .001 for readers 1, 2, 4, and 5; P = .016 for reader 3) without a significant change in sensitivity. CONCLUSION Combined use of US elastography and color Doppler US increases both the accuracy in distinguishing benign from malignant masses and the specificity in decision-making for biopsy recommendation at B-mode US.

Differentiation of benign from malignant nonpalpable breast masses: A comparison of computer-assisted quantification and visual assessment of lesion stiffness with the use of sonographic elastography

Background: Elastography has shown potential in differentiating benign from malignant breast tumors, but interobserver variability between experienced and inexperienced readers limits its wide usage. Purpose: To compare the diagnostic performance of computer-assisted quantification and visual assessment of lesion stiffness with the use of sonographic elastography for the differentiation of benign from malignant nonpalpable breast masses. Material and Methods: Sonographic elasticity images of 120 nonpalpable breast masses (70 benign and 50 malignant masses) were obtained in 120 women prior to performing a core biopsy. After subtraction of B-mode images from color elasticity images, the mean strain value of the lesion was computed. Elasticity images were also reviewed and were assigned a score on a five-point scale by two breast radiologists in consensus. Results were evaluated by using receiver operating characteristic (ROC) curve analysis. Results: The mean ± standard deviation values of strain were 221±18 for malignant lesions and 175±21 for benign lesions (P<0.001). For the elasticity score, the mean score was 3.5±0.1 for the malignant masses and 2.0±0.9 for the benign masses (P<0.001). The overall Pearsons correlation coefficient between the strain values and elasticity score was 0.689 (P<0.001). The area under the ROC curve (Az) value was 0.878 for use of the computer-assisted quantification method and 0.850 for visual assessment by the radiologists. The difference was not statistically significant (P=0.198). Conclusion: Computer-assisted quantification and visual assessment of lesion stiffness with the use of sonographic elasticity images had comparable diagnostic performance for the differentiation of nonpalpable breast masses.

Computer-Aided Evaluation of Breast MRI for the Residual Tumor Extent and Response Monitoring in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

Objective To evaluate the accuracy of a computer-aided evaluation program (CAE) of breast MRI for the assessment of residual tumor extent and response monitoring in breast cancer patients receiving neoadjuvant chemotherapy. Materials and Methods Fifty-seven patients with breast cancers who underwent neoadjuvant chemotherapy before surgery and dynamic contrast enhanced MRI before and after chemotherapy were included as part of this study. For the assessment of residual tumor extent after completion of chemotherapy, the mean tumor diameters measured by radiologists and CAE were compared to those on histopathology using a paired student t-test. Moreover, the agreement between unidimensional (1D) measurement by radiologist and histopathological size or 1D measurement by CAE and histopathological size was assessed using the Bland-Altman method. For chemotherapy monitoring, we evaluated tumor response through the change in the 1D diameter by a radiologist and CAE and three-dimensional (3D) volumetric change by CAE based on Response Evaluation Criteria in Solid Tumors (RECIST). Agreement between the 1D response by the radiologist versus the 1D response by CAE as well as by the 3D response by CAE were evaluated using weighted kappa (k) statistics. Results For the assessment of residual tumor extent after chemotherapy, the mean tumor diameter measured by radiologists (2.0 ± 1.7 cm) was significantly smaller than the mean histological diameter (2.6 ± 2.3 cm) (p = 0.01), whereas, no significant difference was found between the CAE measurements (mean = 2.2 ± 2.0 cm) and histological diameter (p = 0.19). The mean difference between the 1D measurement by the radiologist and histopathology was 0.6 cm (95% confidence interval: -3.0, 4.3), whereas the difference between CAE and histopathology was 0.4 cm (95% confidence interval: -3.9, 4.7). For the monitoring of response to chemotherapy, the 1D measurement by the radiologist and CAE showed a fair agreement (k = 0.358), while the 1D measurement by the radiologist and 3D measurement by CAE showed poor agreement (k = 0.106). Conclusion CAE for breast MRI is sufficiently accurate for the assessment of residual tumor extent in breast cancer patients receiving neoadjuvant chemotherapy. However, for the assessment of response to chemotherapy, the assessment by the radiologist and CAE showed a fair to poor agreement.

Feasibility of Sentinel Lymph Node Biopsy in Breast Cancer Patients with Initial Axillary Lymph Node Metastasis after Primary Systemic Therapy

Purpose Primary systemic therapy (PST) downstages up to 40% of initial documented axillary lymph node (ALN) metastases in breast cancer. The current surgical treatment after PST consists of breast tumor resection and axillary lymph node dissection (ALND). This strategy, however, does not eliminate unnecessary ALND in patients with complete remission of axillary metastases. The aim of this study was to examine the accuracy of sentinel lymph node biopsy (SLNB) after PST among patients with documented ALN metastasis at presentation and to identify the rate of pathologic complete-remission (CR) with ALN after PST. Methods We analyzed 66 patients with ALN metastasis that was pathologically proven preoperatively who underwent SLNB and concomitant ALND after PST. Axillary ultrasound (AUS) was used to evaluate the clinical response of initially documented ALN metastasis after PST. Intraoperative lymphatic mapping was performed using blue dye with or without radioisotope. Results After PST, 34.8% of patients had clinical CR of ALN on AUS and 28.8% patients had pathologic CR of ALN. The overall success rate of SLNB after PST was 87.9%, and the sentinel lymph node identification rate in patients with clinical CR was 95.7%. In patients with successful lymphatic mapping, 70.7% of patients had residual axillary metastases. The overall accuracy and false-negative rate were 87.9% and 17.1% in all patients: 95.5% and 10.0% in patients with clinical CR of ALN, and 83.3% and 19.4% in patients with residual axillary disease after PST. Conclusion Our findings suggest that SLNB may be feasible in patients with initial documented ALN metastasis who have clinical CR for metastatic ALN after PST. Further investigation in a prospective setting should be performed to confirm our results.

Differentiating Benign From Malignant Thyroid Nodules Comparison of 2- and 3- Dimensional Sonography

To compare the diagnostic performance of radiologists and to determine interobserver and intraobserver variability with regard to differentiation of benign and malignant thyroid nodules using prospectively obtained 2‐dimensional (2D) and 3‐dimensional (3D) sonograms.

Comparison of Sonography With Sonographically Guided Fine-Needle Aspiration Biopsy and Core-Needle Biopsy for Initial Axillary Staging of Breast Cancer

The purpose of this study was to determine the roles of sonography and sonographically guided fine‐needle aspiration biopsy and core‐needle biopsy for initial axillary staging of breast cancer.

The Management Strategy of Benign Solitary Intraductal Papilloma on Breast Core Biopsy

Background Intraductal papilloma (IDP) is well‐known as one of the common benign breast lesions requiring excision. However, treatment of IDP without atypia is controversial. The aim of our study was to determine the proper management of solitary IDP by core needle biopsy (CNB). Patients and Methods We retrospectively reviewed patients with solitary IDP confirmed by CNB from March 2003 to March 2015. We collected data about final pathology after excision, as well as clinical, histologic, and radiologic findings at initial diagnosis. The final pathology was categorized as benign or malignant. We evaluated the rate of upgrade to malignancy and factors associated with malignancy. Results We identified 405 patients who presented benign solitary IDP by CNB. The mean age was 46.1 years (range, 15‐86 years). In total, 135 patients underwent surgical excision, and 211 underwent vacuum‐assisted excision. Of 346 patients, malignant lesions were found in 8 patients (2.3%): 7 underwent surgical excision, and 1 underwent vacuum‐assisted excision. Only the size of IDP was significantly associated with cancer upgrade (P = .003). Conclusions Our study shows that overall malignancy upgrade rate of benign solitary IDP after excision is very low (2.3%). Even when the size of IDP was less than 1 cm, the upgrade rate to cancer was only 0.9%. Therefore, for patients with small solitary IDP, we recommend close follow‐up with ultrasound instead of excision. Micro‐Abstract We evaluated cancer upgrade rate of intraductal papilloma (IDP) without atypia after excision for 346 patients. Overall upgrade rate was 2.3%. Mass size was the only predictor for cancer. Higher upgrade rate was observed in patients with a larger mass (> 2 cm: 15.8%, 1‐2 cm: 3.0%, and ≤ 1 cm: 0.9%). Our study suggested that small (≤ 1 cm) IDP without atypia could be followed‐up.

MRI-Guided Intervention for Breast Lesions Using the Freehand Technique in a 3.0-T Closed-Bore MRI Scanner: Feasibility and Initial Results

Objective To report the feasibility of magnetic resonance imaging (MRI)-guided intervention for diagnosing suspicious breast lesions detectable by MRI only, using the freehand technique with a 3.0-T closed-bore MRI scanner. Materials and Methods Five women with 5 consecutive MRI-only breast lesions underwent MRI-guided intervention: 3 underwent MRI-guided needle localization and 2, MRI-guided vacuum-assisted biopsy. The interventions were performed in a 3.0-T closed-bore MRI system using a dedicated phased-array breast coil with the patients in the prone position; the freehand technique was used. Technical success and histopathologic outcome were analyzed. Results MRI showed that four lesions were masses (mean size, 11.5 mm; range, 7-18 mm); and 1, a nonmass-like enhancement (maximum diameter, 21 mm). The locations of the lesions with respect to the breast with index cancer were as follows: different quadrant, same breast - 3 cases; same quadrant, same breast - 1 case; and contralateral breast - 1 case. Histopathologic evaluation of the lesions treated with needle localization disclosed perilobular hemangioma, fibrocystic change, and fibroadenomatous change. The lesions treated with vacuum-assisted biopsy demonstrated a radial scar and atypical apocrine hyperplasia. Follow-up MRI after 2-7 months (mean, 4.6 months) confirmed complete lesion removal in all cases. Conclusion MRI-guided intervention for breast lesions using the freehand technique with a 3.0-T closed-bore MRI scanner is feasible and accurate for diagnosing MRI-only lesions.

Does ultrasound-guided directional vacuum-assisted removal help eliminate abnormal nipple discharge in patients with benign intraductal single mass?

Objective To evaluate whether the removal of an intraductal mass using an ultrasound (US)-guided directional vacuum-assisted device can eliminate symptoms in patients presenting with abnormal nipple discharge. Materials and Methods Between March 2004 and October 2006, 36 patients who presented with abnormal nipple discharge, underwent US-guided, 11-gauge vacuum-assisted biopsy for a benign intraductal single mass on US. The ability of the procedure to eliminate nipple discharge was evaluated by physical examination during follow-up US. Lesion characteristics, biopsy variables, and histologic features were analyzed to identify factors affecting symptom resolution. Results Of the 36 lesions, 25 (69%) were intraductal papillomas, 10 (28%) were fibrocystic changes, and one (3%) was a fibroadenoma. The nipple discharge disappeared in 69% (25 of 36) of the women at a mean follow-up time of 25 months (range 12-42 month). There was no difference in the lesion characteristics, biopsy variables, and the histologic features between groups that eliminated the symptom compared those with persistent nipple discharge. Conclusion US-guided directional vacuum-assisted removal of an intraductal mass appears to eliminate nipple discharge in only 69% of patients and thus, it should not be considered as an alternative to surgical excision.