Radiation Dose Reduction in Digital Mammography by Deep-Learning Algorithm Image Reconstruction: A Preliminary Study

Purpose@#To develop a denoising convolutional neural network-based image processing technique and investigate its efficacy in diagnosing breast cancer using low-dose mammography imaging. @*Materials and Methods@#A total of 6 breast radiologists were included in this prospective study. All radiologists independently evaluated low-dose images for lesion detection and rated them for diagnostic quality using a qualitative scale. After application of the denoising network, the same radiologists evaluated lesion detectability and image quality. For clinical application, a consensus on lesion type and localization on preoperative mammographic examinations of breast cancer patients was reached after discussion. Thereafter, coded low-dose, reconstructed full-dose, and full-dose images were presented and assessed in a random order. @*Results@#Lesions on 40% reconstructed full-dose images were better perceived when compared with low-dose images of mastectomy specimens as a reference. In clinical application, as compared to 40% reconstructed images, higher values were given on full-dose images for resolution (p < 0.001); diagnostic quality for calcifications (p < 0.001); and for masses, asymmetry, or architectural distortion (p = 0.037). The 40% reconstructed images showed comparable values to 100% full-dose images for overall quality (p = 0.547), lesion visibility (p = 0.120), and contrast (p = 0.083), without significant differences. @*Conclusion@#Effective denoising and image reconstruction processing techniques can enable breast cancer diagnosis with substantial radiation dose reduction.

Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Receiving Neoadjuvant Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab / 한국유방암학회지

Purpose@#The tumor-infiltrating lymphocytes (TILs) expression in breast cancer is a positive prognostic marker for certain breast cancer subtypes. We evaluated the efficacy of dual antihuman epidermal growth factor receptor 2 (HER2) blockade in HER2-positive breast cancer and hypothesized that high TILs tumors are associated with better outcomes. @*Methods@#A total of 176 patients who were treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) between December 2015 and December 2018 were reviewed. They were grouped based on a cut-off value of the stromal TILs grade (≤ 20% TILs, > 20% TILs). @*Results@#In total, 107 patients (60.8%) achieved pathological complete response (pCR).Hormone receptor (HR)-negativity (p = 0.001) and a high TILs grade (p = 0.022) were independent predictors of pCR. Among the HR-negative patients, high TILs tumors were significantly associated with pCR (p = 0.035). @*Conclusion@#HR status and the TILs grade are significantly correlated with pCR in dual anti-HER2 neoadjuvant therapy. The evaluation of the TILs at baseline may be beneficial for predicting pCR in HER2-positive breast cancer.

Diffusion-Weighted Magnetic Resonance Imaging for Breast Cancer Screening in High-Risk Women: Design and Imaging Protocol of a Prospective Multicenter Study in Korea / 한국유방암학회지

Purpose@#Interest in unenhanced magnetic resonance imaging (MRI) screening for breast cancer is growing due to concerns about gadolinium deposition in the brain and the high cost of contrast-enhanced MRI. The purpose of this report is to describe the protocol of the Diffusion-Weighted Magnetic Resonance Imaging Screening Trial (DWIST), which is a prospective, multicenter, intraindividual comparative cohort study designed to compare the performance of mammography, ultrasonography, dynamic contrast-enhanced (DCE) MRI, and diffusion-weighted (DW) MRI screening in women at high risk of developing breast cancer. @*Methods@#A total of 890 women with BRCA mutation or family history of breast cancer and lifetime risk ≥ 20% are enrolled. The participants undergo 2 annual breast screenings with digital mammography, ultrasonography, DCE MRI, and DW MRI at 3.0 T. Images are independently interpreted by trained radiologists. The reference standard is a combination of pathology and 12-month follow-up. Each image modality and their combination will be compared in terms of sensitivity, specificity, accuracy, positive predictive value, rate of invasive cancer detection, abnormal interpretation rate, and characteristics of detected cancers. The first participant was enrolled in April 2019. At the time of manuscript submission, 5 academic medical centers in South Korea are actively enrolling eligible women and a total of 235 women have undergone the first round of screening. Completion of enrollment is expected in 2022 and the results of the study are expected to be published in 2026.Discussion: DWIST is the first prospective multicenter study to compare the performance of DW MRI and conventional imaging modalities for breast cancer screening in high-risk women. DWIST is currently in the patient enrollment phase.

Comparison of the Imaging Features of Lobular Carcinoma In Situ and Invasive Lobular Carcinoma of the Breast

Purpose@#To investigate the usefulness of imaging features for differentiating between small lobular carcinoma in situ (LCIS) and invasive lobular carcinoma (ILC). @*Materials and Methods@#It included 52 female with LCISs (median 45 years, range 32–67 years) and 180 female with ILCs (median 49 years, range 36–75 years), with the longest diameter of ≤ 2 cm, who were evaluated between January 2012 and December 2016. All the female underwent mammography and ultrasonography. Twenty female with LCIS and 150 female with ILC underwent MRI. The clinical and imaging features were compared, and multivariate analysis was performed to identify the independent predictors of LCIS. Female with LCIS were also subgrouped by lesion size and compared with the female with ILC. @*Results@#Multivariate analysis showed that younger age (odds ratio [OR] = 1.100), smaller lesion size (OR = 1.103), oval or round shape (OR = 4.098), parallel orientation (OR = 5.464), and isoechotexture (OR = 3.360) were significant independent factors predictive of LCIS. The area under the receiver operating characteristic curve for distinguishing LCIS from ILC was 0.904 (95% confidence interval, 0.857–0.951). Subgroup analysis showed that benign features were more prevalent in female with smaller LCISs (≤ 1 cm) than in those with ILC. @*Conclusion@#Small LCISs tend to demonstrate more benign features than small ILCs. Several imaging features are independently predictive of LCIS.

Imaging Protocol and Criteria for Evaluation of Axillary Lymph Nodes in the NAUTILUS Trial / 한국유방암학회지

Axillary ultrasonography (US) is the most commonly used imaging modality for nodal evaluation in patients with breast cancer. No Axillary Surgical Treatment in Clinically Lymph Node-Negative Patients after Ultrasonography (NAUTILUS) is a prospective, multicenter, randomized controlled trial investigating whether sentinel lymph node biopsy (SLNB) can be safely omitted in patients with clinically and sonographically node-negative T1–2 breast cancer treated with breast-conserving therapy. In this trial, a standardized imaging protocol and criteria were established for the evaluation of axillary lymph nodes. Women lacking palpable lymph nodes underwent axillary US to dismiss suspicious nodal involvement.Patients with a round hypoechoic node with effaced hilum or indistinct margins were excluded. Patients with T1 tumors and a single node with a cortical thickness ≥ 3 mm underwent US-guided biopsy. Finally, patients with negative axillary US findings were included. The NAUTILUS axillary US nodal assessment criteria facilitate the proper selection of candidates who can omit SLNB.

Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Receiving Neoadjuvant Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab / 한국유방암학회지

Purpose@#The tumor-infiltrating lymphocytes (TILs) expression in breast cancer is a positive prognostic marker for certain breast cancer subtypes. We evaluated the efficacy of dual antihuman epidermal growth factor receptor 2 (HER2) blockade in HER2-positive breast cancer and hypothesized that high TILs tumors are associated with better outcomes. @*Methods@#A total of 176 patients who were treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) between December 2015 and December 2018 were reviewed. They were grouped based on a cut-off value of the stromal TILs grade (≤ 20% TILs, > 20% TILs). @*Results@#In total, 107 patients (60.8%) achieved pathological complete response (pCR).Hormone receptor (HR)-negativity (p = 0.001) and a high TILs grade (p = 0.022) were independent predictors of pCR. Among the HR-negative patients, high TILs tumors were significantly associated with pCR (p = 0.035). @*Conclusion@#HR status and the TILs grade are significantly correlated with pCR in dual anti-HER2 neoadjuvant therapy. The evaluation of the TILs at baseline may be beneficial for predicting pCR in HER2-positive breast cancer.

Diffusion-Weighted Magnetic Resonance Imaging for Breast Cancer Screening in High-Risk Women: Design and Imaging Protocol of a Prospective Multicenter Study in Korea / 한국유방암학회지

Purpose@#Interest in unenhanced magnetic resonance imaging (MRI) screening for breast cancer is growing due to concerns about gadolinium deposition in the brain and the high cost of contrast-enhanced MRI. The purpose of this report is to describe the protocol of the Diffusion-Weighted Magnetic Resonance Imaging Screening Trial (DWIST), which is a prospective, multicenter, intraindividual comparative cohort study designed to compare the performance of mammography, ultrasonography, dynamic contrast-enhanced (DCE) MRI, and diffusion-weighted (DW) MRI screening in women at high risk of developing breast cancer. @*Methods@#A total of 890 women with BRCA mutation or family history of breast cancer and lifetime risk ≥ 20% are enrolled. The participants undergo 2 annual breast screenings with digital mammography, ultrasonography, DCE MRI, and DW MRI at 3.0 T. Images are independently interpreted by trained radiologists. The reference standard is a combination of pathology and 12-month follow-up. Each image modality and their combination will be compared in terms of sensitivity, specificity, accuracy, positive predictive value, rate of invasive cancer detection, abnormal interpretation rate, and characteristics of detected cancers. The first participant was enrolled in April 2019. At the time of manuscript submission, 5 academic medical centers in South Korea are actively enrolling eligible women and a total of 235 women have undergone the first round of screening. Completion of enrollment is expected in 2022 and the results of the study are expected to be published in 2026.Discussion: DWIST is the first prospective multicenter study to compare the performance of DW MRI and conventional imaging modalities for breast cancer screening in high-risk women. DWIST is currently in the patient enrollment phase.

Comparison of the Imaging Features of Lobular Carcinoma In Situ and Invasive Lobular Carcinoma of the Breast

Purpose@#To investigate the usefulness of imaging features for differentiating between small lobular carcinoma in situ (LCIS) and invasive lobular carcinoma (ILC). @*Materials and Methods@#It included 52 female with LCISs (median 45 years, range 32–67 years) and 180 female with ILCs (median 49 years, range 36–75 years), with the longest diameter of ≤ 2 cm, who were evaluated between January 2012 and December 2016. All the female underwent mammography and ultrasonography. Twenty female with LCIS and 150 female with ILC underwent MRI. The clinical and imaging features were compared, and multivariate analysis was performed to identify the independent predictors of LCIS. Female with LCIS were also subgrouped by lesion size and compared with the female with ILC. @*Results@#Multivariate analysis showed that younger age (odds ratio [OR] = 1.100), smaller lesion size (OR = 1.103), oval or round shape (OR = 4.098), parallel orientation (OR = 5.464), and isoechotexture (OR = 3.360) were significant independent factors predictive of LCIS. The area under the receiver operating characteristic curve for distinguishing LCIS from ILC was 0.904 (95% confidence interval, 0.857–0.951). Subgroup analysis showed that benign features were more prevalent in female with smaller LCISs (≤ 1 cm) than in those with ILC. @*Conclusion@#Small LCISs tend to demonstrate more benign features than small ILCs. Several imaging features are independently predictive of LCIS.

Automated Breast Ultrasound Screening for Dense Breasts

The Usefulness of Periareolar Zigzag Incision in Breast Conserving-Surgery in Breast Cancer Patients: Experience in a Single Institution

Purpose@#Various incision techniques have been used in breast-conserving surgery (BCS) to reduce scar formation, including the frequently used periareolar incision technique. However, its applicability in removing large-size tumors or those distant from the nipple has remained limited. We performed periareolar zigzag (P-Z) incision to address these problems in BCS and to improve cosmetic outcomes. @*Methods@#Patients who underwent P-Z incision in BCS between January 2016 and November 2017 were retrospectively analyzed in terms of clinicopathological features and surgical findings. Factors affecting the positive margin were analyzed. @*Results@#A total of 305 patients were reviewed. The patients presented with a median age of 51 years, mean tumor size 1.9 cm, and mean tumor distance of 3.3 cm from the nipple. Intraoperative frozen biopsy and final pathologic findings showed 43 (14.1%) and 7 (2.3%) tumor-positive margins. There were no major complications associated with the surgery, and no re-operations were required due to bleeding or other reasons. @*Conclusion@#The P-Z incision technique was used to achieve sufficient operative field during BCS, and large tumors or those distant from the nipple could be removed without any complications. This technique is considered an oncologically safe surgical technique resulting in good cosmetic outcomes.

Digital Breast Tomosynthesis Screening

Digital breast tomosynthesis (DBT) has been shown to be a promising imaging technique for breast cancer detection. DBT involves acquisition of a series of images in different planes over a limited angular range, and their subsequent reconstruction into a quasi-three-dimensional breast volume. This reduces the effects of tissue overlap. This review aims to describe the key features of DBT, including technique, results from recent retrospective and prospective clinical studies, and issues with DBT as a screening tool.

Sonographic features that can be used to differentiate between small triple-negative breast cancer and fibroadenoma

PURPOSE: Our study investigated whether any sonographic findings could be useful for differentiating between small triple-negative breast cancer (TNBC) and fibroadenoma. METHODS: This retrospective study was approved by our Institutional Review Board, which waived the requirement for patient consent. From January 2009 to December 2010, the sonographic features of 181 pathologically proven TNBC tumors and 172 fibroadenomas measuring less than or equal to 2 cm in the longest dimension were reviewed and analyzed according to the fifth edition of the Breast Imaging Reporting and Data System (BI-RADS) lexicon. Mean tumor roundness was also measured using in-house software. RESULTS: The median longest lesion dimension was 16 mm (range, 13 to 18 mm) in TNBCs and 13 mm (range, 10 to 16 mm) in fibroadenomas. In comparison to fibroadenomas, small TNBC tumors presented with a higher incidence of irregular shapes (66.9%), noncircumscribed margins (91.7%), hypoechoic echotexture (59.1%), posterior acoustic enhancement (65.2%), and associated features (24.4%). Most TNBCs were classified as BI-RADS category 4 (65.2%) or 5 (28.2%). The mean tumor roundness of small TNBCs was greater than that of fibroadenomas (60%±12% vs. 53%±13%). Multivariate analysis showed that older patient age, irregular shape, nonparallel orientation, posterior acoustic enhancement, associated features, a BI-RADS final assessment category of 4 or 5, and greater tumor roundness were significant independent factors indicative of TNBCs. CONCLUSION: TNBC tumors tend to demonstrate more suspicious sonographic features and greater tumor roundness than fibroadenomas. These features may have the potential to help differentiate between small TNBCs and fibroadenomas.

Predicting Successful Conservative Surgery after Neoadjuvant Chemotherapy in Hormone Receptor-Positive, HER2-Negative Breast Cancer

PURPOSE: This study aimed to determine whether clinicopathological factors are potentially associated with successful breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) and develop a nomogram for predicting successful BCS candidates, focusing on those who are diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors during the pre-NAC period. METHODS: The training cohort included 239 patients with an HR-positive, HER2-negative tumor (≥3 cm), and all of these patients had received NAC. Patients were excluded if they met any of the following criteria: diffuse, suspicious, malignant microcalcification (extent >4 cm); multicentric or multifocal breast cancer; inflammatory breast cancer; distant metastases at the time of diagnosis; excisional biopsy prior to NAC; and bilateral breast cancer. Multivariate logistic regression analysis was conducted to evaluate the possible predictors of BCS eligibility after NAC, and the regression model was used to develop the predicting nomogram. This nomogram was built using the training cohort (n=239) and was later validated with an independent validation cohort (n=123). RESULTS: Small tumor size (p < 0.001) at initial diagnosis, long distance from the nipple (p=0.002), high body mass index (p=0.001), and weak positivity for progesterone receptor (p=0.037) were found to be four independent predictors of an increased probability of BCS after NAC; further, these variables were used as covariates in developing the nomogram. For the training and validation cohorts, the areas under the receiver operating characteristic curve were 0.833 and 0.786, respectively; these values demonstrate the potential predictive power of this nomogram. CONCLUSION: This study established a new nomogram to predict successful BCS in patients with HR-positive, HER2-negative breast cancer. Given that chemotherapy is an option with unreliable outcomes for this subtype, this nomogram may be used to select patients for NAC followed by successful BCS.

Ectopic Male Breast Cancer in the Perineum: A Case Report / 한국유방암학회지

Ectopic breast tissue and male breast cancer are both very rare diseases with only a few reports in the literature. Here, we present the first case of ectopic male breast cancer in the perineum. The patient was a 70-year-old man with a palpable mass in the perineum. A wide local excision and inguinal lymph node dissection revealed invasive breast carcinoma of no special type involving the skin and subcutis, and inguinal lymph node metastases. Immunohistochemical staining showed that the tumor cells were strongly positive for estrogen and progesterone receptors and negative for human epidermal growth factor receptor 2. Moreover, no p53 overexpression was observed. Herein, the clinical and pathologic features, as well as a review of ectopic male breast cancer are discussed.

Simplified computer-aided detection scheme of microcalcification clusters in digital breast tomosynthesis images.

A computer-aided detection (CADe) algorithm for clustered microcalcifications (MCs) in reconstructed digital breast tomosynthesis (DBT) images is suggested. The MC-like objects were enhanced by a Hessian-based 3D calcification response function, and a signal-to-noise ratio (SNR) enhanced image was also generated to screen the MC clustering seed objects. A connected component segmentation method was used to detect the cluster seed objects, which were considered as potential clustering centers of MCs. Bounding cubes for the accepted clustering seed candidate were generated and the overlapping cubes were combined and examined. After the MC clustering and false-positive (FP) reduction step, the average number of FPs was estimated to be 0.87 per DBT volume with a sensitivity of 90.5%.

A Randomized Phase II Trial of Capecitabine Plus Vinorelbine Followed by Docetaxel Versus Adriamycin Plus Cyclophosphamide Followed by Docetaxel as Neoadjuvant Chemotherapy for Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Given the promising activity of capecitabine and vinorelbine in metastatic breast cancer, this randomized phase II trial evaluated the efficacy and safety of this combination as neoadjuvant chemotherapy in breast cancer. MATERIALS AND METHODS: Patients with operable breast cancer (n=75) were randomly assigned to receive either four cycles of adriamycin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks followed by four cycles of docetaxel 75 mg/m2 every 3 weeks (AC-D) or four cycles of capecitabine 2,000 mg/m2 (day 1-14) plus vinorelbine 25 mg/m2 (days 1 and 8) every 3 weeks followed by four cycles of docetaxel 75 mg/m2 (CV-D). The primary endpoint was pathologic complete response (pCR) in the primary breast (ypT0/is). RESULTS: Most patients (84%) had locally advanced (n=41) or inflammatory breast cancer (n=22). pCR rates in the primary breast were 15% (95% confidence interval [CI], 7% to 30%) and 11% (95% CI, 4% to 26%) in the AC-D and CV-D groups, respectively. The overall response rates and 5-year progression-free survival rates in the AC-D and CV-D groups were 62% and 64%, and 51.3% (95% CI, 34.6% to 68.0%) and 30.2% (95% CI, 13.3% to 47.1%), respectively. Although both regimens were well tolerated, CV-D showed less frequent grade 3-4 neutropenia and vomiting than AC-D, whereas manageable diarrhea and hand-foot syndrome were more common in the CV-D group. CONCLUSION: CV-D is a feasible and active non-anthracycline-based neoadjuvant chemotherapy regimen for breast cancer.

Second-look ultrasonography for MRI-detected suspicious breast lesions in patients with breast cancer

PURPOSE: The purpose of this study is to evaluate the use of second-look ultrasonography (US) for investigating additional suspicious lesions detected on preoperative staging magnetic resonance imaging (MRI) for breast cancer. METHODS: Between September 2008 and August 2010, 1,970 breast MRIs were performed at our medical institution for the evaluation of breast cancer before surgery. Second-look US was recommended for 135 patients with 149 suspicious lesions, following the MRI interpretation, and 108 patients with 121 lesions were included in this study. The detection rate on second-look US, according to the lesion type, diameter, and histopathological outcome, was analyzed. RESULTS: Of the 121 lesions considered in this study, 97 (80.2%) were diagnosed on MRI as masses and 24 (19.8%) as non-mass-like lesions; 105 lesions (86.8%) were correlated and 16 (13.2%) were not correlated with the findings of second-look US. Of the 105 correlated lesions, 29 (27.6%) were proven to be malignant and 76 (72.4%) were benign. Although a greater number of large malignant lesions were correlated on second-look US than small benign lesions, there was no statistically significant difference according to lesion diameter or type, as seen on MRI or pathology. CONCLUSION: We have concluded that second-look US is a useful diagnostic tool for lesions incidentally detected on breast MRI, as in this study, it could identify 86.8% of the MRI-detected breast lesions.

Current status of automated breast ultrasonography

Breast ultrasonography (US) is currently considered the first-line examination in the detection Epub ahead of print and characterization of breast lesions. However, conventional handheld US (HHUS) has several limitations such as operator dependence and the requirement of a considerable amount of radiologist time for whole-breast US. Automated breast US (ABUS), recently approved by the United States Food and Drug Administration for screening purposes, has several advantages over HHUS, such as higher reproducibility, less operator dependence, and less required physician time for image acquisition. In addition, ABUS provides both a coronal view and a relatively large field of view. Recent studies have reported that ABUS is promising in US screening for women with dense breasts and can potentially replace handheld second-look US in a preoperative setting.

Complex Hemangioma of the Breast: Case Report, with Imaging Findings

Vascular tumors in the breast are rare, and most can be classified as being either angiosarcomas or hemangiomas. Hemangiomas are benign vascular tumors that are usually identified incidentally. Here, we are reporting on a case of a complex hemangioma of the breast, and describing the mammography, ultrasonography, and magnetic resonance imaging findings for this patient.

Reliability of the Percent Density in Digital Mammography with a Semi-Automated Thresholding Method / 한국유방암학회지

PURPOSE: The reliability of the quantitative measurement of breast density with a semi-automated thresholding method (Cumulus(TM)) has mainly been investigated with film mammograms. This study aimed to evaluate the intrarater reproducibility of percent density (PD) by Cumulus(TM) with digital mammograms. METHODS: This study included 1,496 craniocaudal digital mammograms from the unaffected breast of breast cancer patients. One rater reviewed each mammogram and estimated the PD using the Cumulus(TM) method. All images were reassessed by the same rater 1 month later without reference to the previously assigned values. The repeatability of the PD was evaluated by an intraclass correlation coefficient (ICC). All patients were grouped based on their body mass index (BMI), age, family history of breast cancer, breastfeeding history and breast area (calculated with Cumulus(TM)), and subgroup analysis for the ICC of each group was performed. All patients were categorized by their Breast Imaging Reporting and Data System (BI-RADS) density pattern, and the mean and standard deviation of the PD by each BI-RADS categories were compared. RESULTS: The ICC for the PD was 0.94, indicating excellent repeatability. The discrepancy between the paired PD values ranged from 0 to 23.93, with an average of 3.90 (standard deviation=3.39). The subgroup ICCs for the PD ranged from 0.88 to 0.96, indicating excellent reliability in all subgroups regardless of patient variables. The ICCs of the PD for the high-risk (BI-RADS 3 and 4) and low-risk (BI-RADS 1 and 2) groups were 0.90 and 0.88, respectively. CONCLUSION: This study suggests that PD calculated with digital mammograms has an acceptable reliability regardless of patient age, BMI, family history of breast cancer, breastfeeding history, breast size, and BI-RADS density pattern.