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A clinical trial was conducted to assess the feasibility of enrolling patients with Stage II or III hormone receptor positive (HR+)/HER2-negative breast cancer to pre-operative dual PD-L1/CTLA-4 checkpoint inhibition administered prior to neoadjuvant chemotherapy (NACT). Eight eligible patients were treated with upfront durvalumab and tremelimumab for two cycles. Patients then received NACT prior to breast surgery. Seven patients had baseline and interval breast ultrasounds after combination immunotherapy and the responses were mixed: 3/7 patients experienced a ≥30% decrease in tumor volume, 3/7 a ≥30% increase, and 1 patient had stable disease. At the time of breast surgery, 1/8 patients had a pathologic complete response (pCR). The trial was stopped early after 3 of 8 patients experienced immunotherapy-related toxicity or suspected disease progression that prompted discontinuation or a delay in the administration of NACT. Two patients experienced grade 3 immune-related adverse events (1 with colitis, 1 with endocrinopathy). Analysis of the tumor microenvironment after combination immunotherapy did not show a significant change in immune cell subsets from baseline. There was limited benefit for dual checkpoint blockade administered prior to NACT in our study of 8 patients with HR+/HER2-negative breast cancer.

Surgical treatment for breast cancer has evolved from radical mastectomy to modified radical mastectomy to breast-conserving surgery. As the de-escalation of surgical treatment for breast cancer continues, nonsurgical treatment for early-stage breast cancer with favorable ancillary features (low grade, positivity for hormone receptors) is being explored. Of the nonsurgical treatment options, cryoablation has demonstrated the greatest appeal, proven to be effective, safe, well tolerated, and feasible in an outpatient setting with local anesthetic alone. Results of past and interim results of current trials of cryoablation of stage I low-grade breast cancer with curative intent are promising, with an overall clinical success rate of 98% and recurrence rates consistent with those expected following lumpectomy. Cryoablation is also an alternative palliative treatment for patients who cannot tolerate or who have disease that is refractory to or recurs after standard-of-care breast cancer treatment and may have immunological therapeutic effects, warranting future research. Understanding the indications and optimal technique for breast cancer cryoablation and understanding typical imaging findings after cryoablation are essential to ensure the success of the procedure in carefully selected patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered potential competing interests: the following authors of this manuscript declare relationships with the following companies: Dr. Kenneth Tomokovich is a consultant and on the speakers bureau at IceCure Medical. Dr. Rajani Katta is on the Advisory board at Vichy laboratories (not relevant to content of paper). Dr. Monica Huang receives research funding from Boston Scientific Corporation., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in triple-negative breast cancer (TNBC) is a strong predictor of patient survival. Edema in the peritumoral region (PTR) has been reported to be a negative prognostic factor in TNBC., Purpose: To determine whether quantitative apparent diffusion coefficient (ADC) features from PTRs on reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) predict the response to NAST in TNBC., Study Type: Prospective., Population/subjects: A total of 108 patients with biopsy-proven TNBC who underwent NAST and definitive surgery during 2015-2020., Field Strength/sequence: A 3.0 T/rFOV single-shot diffusion-weighted echo-planar imaging sequence (DWI)., Assessment: Three scans were acquired longitudinally (pretreatment, after two cycles of NAST, and after four cycles of NAST). For each scan, 11 ADC histogram features (minimum, maximum, mean, median, standard deviation, kurtosis, skewness and 10th, 25th, 75th, and 90th percentiles) were extracted from tumors and from PTRs of 5 mm, 10 mm, 15 mm, and 20 mm in thickness with inclusion and exclusion of fat-dominant pixels., Statistical Tests: ADC features were tested for prediction of pCR, both individually using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC), and in combination in multivariable models with k-fold cross-validation. A P value < 0.05 was considered statistically significant., Results: Fifty-one patients (47%) had pCR. Maximum ADC from PTR, measured after two and four cycles of NAST, was significantly higher in pCR patients (2.8 ± 0.69 vs 3.5 ± 0.94 mm 2 /sec). The top-performing feature for prediction of pCR was the maximum ADC from the 5-mm fat-inclusive PTR after cycle 4 of NAST (AUC: 0.74; 95% confidence interval: 0.64, 0.84). Multivariable models of ADC features performed similarly for fat-inclusive and fat-exclusive PTRs, with AUCs ranging from 0.68 to 0.72 for the cycle 2 and cycle 4 scans., Data Conclusion: Quantitative ADC features from PTRs may serve as early predictors of the response to NAST in TNBC., Evidence Level: 1 TECHNICAL EFFICACY: Stage 4., (© 2022 International Society for Magnetic Resonance in Medicine.)

Rationale and Objectives: Synthesized mammography with digital breast tomosynthesis (SM+DBT) and full-field digital mammography with DBT were prospectively evaluated for recall rate (RR), cancer detection rate (CDR), positive predictive value 1 (PPV1), lesion recall differences, and disagreements in recall for additional imaging., Materials and Methods: From December 15, 2015 to January 15, 2017, after informed consent was obtained for this Health Insurance Portability and Accountability Act compliant study, each enrolled patient's SM+DBT and FFDM+DBT were interpreted sequentially by one of eight radiologists. RR, CDR, PPV1, and imaging findings (asymmetry, focal asymmetry, mass, architectural distortion, and calcifications) recalled were reviewed., Results: For SM+DBT and FFDM+DBT in 1022 patients, RR was 7.3% and 7.9% (SM+DBT vs. FFDM+DBT: diff= -0.6%; 90% CI= -1.4%, 0.1%); CDR was 6.8 and 7.8 per 1000 (SM+DBT vs. FFDM+DBT: diff= -1.0, 95% CI= -5.5, 2.8, p = 0.317); PPV1 was 9.3% and 9.9% (relative positive predictive value for SM+DBT vs. FFDM+DBT: 0.95, 95% CI: 0.73-1.22, p = 0.669). FFDM+DBT detected eight cancers; SM+DBT detected seven (missed 1 cancer with calcifications). SM+DBT and FFDM+DBT disagreed on patient recall for additional imaging in 19 patients, with majority (68%, 13/19 patients) in the recall of patients for calcifications. For calcifications, SM+DBT recalled six patients that FFDM+DBT did not recall, and FFDM+DBT recalled seven patients that SM+DBT did not recall, even though the total number of calcifications finding recalled was similar overall for both SM+DBT and FFDM+DBT., Conclusion: Disagreement in recall of patients for calcifications may impact cancer detection by SM+DBT, warranting further investigation., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: Increased levels of stromal tumor-infiltrating lymphocytes (sTILs) have recently been considered a favorable independent prognostic and predictive biomarker in triple-negative breast cancer (TNBC). The purpose of this study was to determine the relationship between BI-RADS (Breast Imaging Reporting and Data System) ultrasound lexicon descriptors and sTILs in TNBC., Materials and Methods: Patients with stage I-III TNBC were evaluated within a single-institution neoadjuvant clinical trial. Two fellowship-trained breast radiologists used the BI-RADS ultrasound lexicon to assess pretreatment tumor shape, margin, echo pattern, orientation, posterior features, and vascularity. sTILs were defined as low <20 or high ≥20 on the pretreatment biopsy. Fisher's exact tests were used to assess the association between lexicon descriptors and sTIL levels., Results: The 284 patients (mean age 52 years, range 24-79 years) were comprised of 68% (193/284) with low-sTIL tumors and 32% (91/284) with high-sTIL tumors. TNBC tumors with high sTILs were more likely to have the following features: (1) oval/round shape than irregular shape (p = 0.003), (2) circumscribed or microlobulated margins than spiculated, indistinct, or angular margins (p = 0.0005); (3) complex cystic and solid pattern than heterogeneous pattern (p = 0.006); and (4) posterior enhancement than shadowing (p = 0.002). There was no significant association between sTILs and descriptors for orientation and vascularity (p = 0.06 and p = 0.49, respectively)., Conclusion: BI-RADS ultrasound descriptors of the pretreatment appearance of a TNBC tumor can be useful in discriminating between tumors with low and high sTIL levels. Therefore, there is a potential use of ultrasound tumor characteristics to complement sTILs when used as stratification factors in treatment algorithms for TNBC., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the acceptability and impact of 3D-printed breast models (3D-BMs) on treatment-related decisional conflict (DC) of breast cancer patients., Methods: Patients with breast cancer were accrued in a prospective institutional review board-approved trial. All patients underwent contrast-enhanced breast magnetic resonance imaging (MRI). A personalized 3D-BM was derived from MRI. DC was evaluated pre- and post-3D-BM review. 3D-BM acceptability was assessed post-3D-BM review., Results: DC surveys before and after 3D-BM review and 3D-BM acceptability surveys were completed by 25 patients. 3D-BM were generated in two patients with bilateral breast cancer. The mean patient age was 48.8 years (28-72). The tumor stage was Tis (7), 1 (8), 2 (8), and 3 (4). The nodal staging was 0 (19), 1 (7), and 3 (1). Tumors were unifocal (15), multifocal (8), or multicentric (4). Patients underwent mastectomy (13) and segmental mastectomy (14) with (20) or without (7) oncoplastic intervention. Neoadjuvant therapy was given to seven patients. Patients rated the acceptability of the 3D-BM as good/excellent in understanding their condition (24/24), understanding disease size (25/25), 3D-BM detail (22/25), understanding their surgical options (24/25), encouraging to ask questions (23/25), 3D-BM size (24/25), and impartial to surgical options (17/24). There was a significant reduction in the overall DC post-3D-BM review, indicating patients became more assured of their treatment choice (p = 0.002). Reduction post-3D-BM review was also observed in the uncertainty (p = 0.012), feeling informed about options (p = 0.005), clarity about values (p = 0.032), and effective (p = 0.002) Decisional Conflict Scale subscales., Conclusions: 3D-BMs are an acceptable tool to decrease DC in breast cancer patients., (© 2021 Wiley Periodicals LLC.)

Purpose: To determine if tumor necrosis by pretreatment breast MRI and its quantitative imaging characteristics are associated with response to NAST in TNBC., Methods: This retrospective study included 85 TNBC patients (mean age 51.8 ± 13 years) with MRI before NAST and definitive surgery during 2010-2018. Each MRI included T2-weighted, diffusion-weighted (DWI), and dynamic contrast-enhanced (DCE) imaging. For each index carcinoma, total tumor volume including necrosis (TTV), excluding necrosis (TV), and the necrosis-only volume (NV) were segmented on early-phase DCE subtractions and DWI images. NV and %NV were calculated. Percent enhancement on early and late phases of DCE and apparent diffusion coefficient were extracted from TTV, TV, and NV. Association between necrosis with pathological complete response (pCR) was assessed using odds ratio (OR). Multivariable analysis was used to evaluate the prognostic value of necrosis with T stage and nodal status at staging. Mann-Whitney U tests and area under the curve (AUC) were used to assess performance of imaging metrics for discriminating pCR vs non-pCR., Results: Of 39 patients (46%) with necrosis, 17 had pCR and 22 did not. Necrosis was not associated with pCR (OR, 0.995; 95% confidence interval [CI] 0.4-2.3) and was not an independent prognostic factor when combined with T stage and nodal status at staging (P = 0.46). None of the imaging metrics differed significantly between pCR and non-pCR in patients with necrosis (AUC < 0.6 and P > 0.40)., Conclusion: No significant association was found between necrosis by pretreatment MRI or the quantitative imaging characteristics of tumor necrosis and response to NAST in TNBC.

Background: Breast cancer is a multifactorial disease that affects women worldwide. Its progression is likely to be executed by oxidative stress wherein elevated levels of reactive oxygen and nitrogen species drive several breast cancer pathologies. Spider venom contains various pharmacological peptides which exhibit selective activity to abnormal expression of ion channels on cancer cell surface which can confer potent anti-cancer activities against this disease., Methods: Venom was extracted from a Philippine tarantula by electrostimulation and fractionated by reverse phase-high performance liquid chromatography (RP-HPLC). Venom fractions were collected and used for in vitro analyses such as cellular toxicity, morphological assessment, and oxidative stress levels., Results: The fractionation of crude spider venom generated several peaks which were predominantly detected spectrophotometrically and colorimetrically as peptides. Treatment of MCF-7 cell line of selected spider venom peptides induced production of several endogenous radicals such as hydroxyl radicals (•OH), nitric oxide radicals (•NO), superoxide anion radicals (•O2-) and lipid peroxides via malondialdehyde (MDA) reaction, which is comparable with the scavenging effects afforded by 400 µg/mL vitamin E and L-cysteine (p<0.05). Concomitantly, the free radicals produced decrease the mitochondrial membrane potential and metabolic activity as detected by rhodamine 123 and tetrazolium dye respectively (p>0.05). This is manifested by cytotoxicity in MCF-7 cells as seen by increase in membrane blebbing, cellular detachment, caspase activity and nuclear fragmentation., Conclusion: These data suggest that the Philippine tarantula venom contains peptide constituents exhibiting pro-oxidative and nitrosative-dependent cytotoxic activities against MCF-7 cells and can indicate mechanistic insights to further explore its potential application as prooxidants in cancer therapy., .

Objective: To determine the relationship between negative margin width and locoregional recurrence (LRR) in a contemporary cohort of ductal carcinoma in situ (DCIS) patients., Background: Recent national consensus guidelines recommend an optimal margin width of 2 mm or greater for the management of DCIS; however, controversy regarding re-excision remains when managing negative margins <2 mm., Methods: One thousand four hundred ninety-one patients with DCIS who underwent breast-conserving surgery from 1996 to 2010 were identified from a prospectively managed cancer center database and analyzed using univariate and multivariate Cox proportional hazard models to determine the relationship between negative margin width and LRR with or without adjuvant radiation therapy (RT)., Results: A univariate analysis revealed that age <40 years (n = 89; P = 0.02), no RT (n = 298; P = 0.01), and negative margin width <2 mm (n = 120; P = 0.005) were associated with LRR. The association between margin width and LRR differed by adjuvant RT status (interaction P = 0.02). There was no statistical significant difference in LRR between patients with <2 mm and ≥2 mm negative margins who underwent RT (10-yr LRR rate, 4.8% vs 3.3%, respectively; hazard ratio, 0.8; 95% CI, 0.2-3.2; P = 0.72). For patients who did not undergo RT, those with margins <2 mm were significantly more likely to develop a LRR than were those with margins ≥2 mm (10-yr LRR rate, 30.9% vs 5.4%, respectively; hazard ratio, 5.5; 95% CI, 1.8-16.8, P = 0.003)., Conclusions: Routine additional surgery may not be justified for patients with negative margins <2 mm who undergo RT but should be performed in patients who forego RT.

Purpose: To investigate clinicopathologic breast cancer characteristics associated with the identification of synchronous bilateral breast cancer (SBBC) on dynamic contrast-enhanced breast magnetic resonance imaging., Methods: We performed a retrospective review of 311 consecutive patients newly diagnosed with breast cancer who underwent diagnostic mammography, ultrasonography, and dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) at our institution. Tumor histology, grade, biomarker status (estrogen receptor, progesterone receptor, and HER2), TNM staging, and unifocal or multifocal/multicentric status were compared between the index tumors in the unilateral disease and the SBBC groups, as well as between the index tumors in the unilateral disease group and the synchronous contralateral tumors (SCT) in the SBBC group, using the Fisher exact test., Results: A total of 326 cancers in 311 patients were reviewed. Fifteen (4.8%) patients were diagnosed with SBBC. The index tumors in patients with SBBC were more frequently lower T stage (p = 0.007), lower grade (p = 0.04), and multifocal/multicentric (p = 0.004) compared with the index tumors in the unilateral group. Biomarkers, N status, and M status did not significantly differ between the index tumors in both groups., Conclusions: SBBC was more likely to be identified in women with lower T stage, lower tumor grade and multifocal/multicentric tumors. Multimodality imaging including DCE-MRI is essential in detection and diagnosis of SBBC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: This study was designed to present the secondary imaging endpoints of the trial for evaluating mammogram (MMG), ultrasound (US) and image guided biopsy (IGBx) assessment of pathologic complete response (pCR) in breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC)., Methods: Patients with T1-3, N0-3, M0 triple-negative or HER2-positive BC who received NAC were enrolled in an Institutional Review Board-approved prospective, clinical trial. Patients underwent US and MMG at baseline and after NAC. Images were evaluated for residual abnormality and to determine modality for IGBx [US-guided (USG) or stereotactic guided (SG)]. Fine-needle aspiration and 9-G, vacuum-assisted core biopsy (VACBx) of tumor bed was performed after NAC and was compared with histopathology at surgery., Results: Forty patients were enrolled. Median age was 50.5 (range 26-76) years; median baseline tumor size was 2.4 cm (range 0.8-6.3) and 1 cm (range 0-5.5) after NAC. Nineteen patients had pCR: 6 (32%) had residual Ca 2+ presurgery, 5 (26%) residual mass, 1 (5%) mass with calcifications, and 7 (37%) no residual imaging abnormality. Sensitivity, specificity, and accuracy of US, MMG, and IGBx for pCR were 47/95/73%, 53/90/73%, and 100/95/98%, respectively. Twenty-five (63%) patients had SGBx and 15 (37%) had US-guided biopsy (USGBx). Median number of cores was higher with SGBx (12, range 6-14) than with USGBx (8, range 4-12), p < 0.002. Positive predictive value for pCR was significantly higher for SG VACBx than for USG VACBx (100 vs. 60%, p < 0.05)., Conclusions: SG VACBx is the preferred IGBx modality for identifying patients with pCR for trials testing the safety of eliminating surgery.

Background Intrinsic molecular profiling of breast cancer provides clinically relevant information that helps tailor therapy directed to the specific tumor subtype. We hypothesized that dynamic contrast-enhanced MRI (DCE-MRI) derived quantitative kinetic parameters (CD-QKPs) may help predict molecular tumor profiles non-invasively. Purpose To determine the association between DCE-MRI (CD-QKPs) and breast cancer clinicopathological prognostic factors. Material and Methods Clinicopathological factors in consecutive women with biopsy-confirmed invasive breast cancer who underwent breast DCE-MRI were retrospectively reviewed. Analysis of variance was used to examine associations between prognostic factors and CD-QKPs. Fisher's exact test was used to investigate the relationship between kinetic curve type and prognostic factors. Results A total of 198 women with invasive breast cancer were included. High-grade and HER2+ tumors were more likely to have a washout type curve while luminal A tumors were less likely. High-grade was significantly associated with increased peak enhancement (PE; P = 0.01), enhancement maximum slope (MS; P = 0.03), and mean enhancement ( ME, P = 0.03), while high clinical lymph node stage (cN3) was significantly associated with increased MS and time to peak (tP; P = 0.01). HER2+ tumors were associated with a higher PE ( P = 0.03) and ME ( P = 0.06) than HER2- counterparts, and ER-/HER2+ tumors showed higher PE and ME values than ER+/HER2- tumors ( P = 0.06). Conclusion DCE-MRI time-intensity CD-QKPs are associated with high tumor grade, advanced nodal stage, and HER2+ status, indicating their utility as imaging biomarkers.

MR imaging is now routinely performed for breast cancer screening and staging. For suspicious MR imaging-detected lesions that are mammographically and sonographically occult, MR imaging-guided breast interventions, including biopsy, clip placement, and preoperative needle localization, have been developed to permit accurate tissue diagnosis and aid in surgical planning. These procedures are safe, accurate, and effective when performed according to key principles, including proper patient selection, use of appropriate technique, adequate preprocedure preparation and postprocedure patient care, and postprocedure imaging-pathology correlation. Imaging-pathology correlation after MR imaging-guided biopsy is essential to confirm accurate sampling and guide development of a comprehensive management plan., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To determine the accuracy of fine-needle aspiration (FNA) and vacuum-assisted core biopsy (VACB) in assessing the presence of residual cancer in the breast after neoadjuvant systemic therapy (NST)., Summary Background Data: Pathologic complete response (pCR) rates after NST have improved dramatically, suggesting that surgery might be avoided in some patients. Safe avoidance of surgery would require accurate confirmation of no residual invasive/in situ carcinoma., Methods: Forty patients with T1-3N0-3 triple-negative or HER2-positive cancer receiving NST were enrolled in this single-center prospective trial. Patients underwent ultrasound-guided or mammography-guided FNA and VACB of the initial breast tumor region before surgery. Findings were compared with findings on pathologic evaluation of surgical specimens to determine the performance of biopsy in predicting residual breast disease after NST., Results: Median initial clinical tumor size was 3.3 cm (range, 1.2-7.0 cm); 16 patients (40%) had biopsy-proven nodal metastases. After NST, median clinical tumor size was 1.1 cm (range, 0-4.2 cm). Nineteen patients (47.5%) had a breast pCR and were concordant with pathologic nodal status in 97.5%. Combined FNA/VACB demonstrated an accuracy of 98% (95% CI, 87%-100%), false-negative rate of 5% (95% CI, 0%-24%), and negative predictive value of 95% (95% CI, 75%-100%) in predicting residual breast cancer. VACB alone was more accurate than FNA alone (P = 0.011)., Conclusions: After NST, image-guided FNA/VACB can accurately identify patients with a breast pCR. Based on these results, a prospective clinical trial has commenced in which breast surgery is omitted in patients with a breast pCR after NST according to image-guided biopsy.

Background: To determine the cancer yield of stereotactic biopsy of suspicious calcifications identified within 24 months after breast conservation therapy (BCT)., Methods: Retrospective review of stereotactic biopsies performed during 2009-2013 for suspicious calcifications in the ipsilateral breast of patients who completed BCT., Results: 94/2773 (3.4%) had stereotactic biopsies for suspicious calcifications in the ipsilateral breast; 7/94 (7.4%) had DCIS (6) or invasive (1) cancer; 5/7 occurred in the same breast quadrant as the primary. All 7 originally had negative surgical margins (≥2 mm); 6 received whole breast irradiation, and 2 received adjuvant chemotherapy + endocrine therapy. Median time to detection was 11 months (range, 6-20 months). There was a strong association between calcification morphology (particularly pleomorphic) and likelihood of malignancy (p = 0.008)., Conclusions: Stereotactic biopsy of calcifications identified within 24 months post-BCT has a 7% cancer yield. Tissue biopsy should be performed rather than imaging followup alone when breast calcifications have suspicious morphology., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To identify clinicopathologic, technical, and imaging features associated with neoplastic seeding (NS) following image-guided needle breast biopsy., Methods: We performed an institutional review board-approved retrospective review of patients presenting with a new diagnosis of breast cancer or suspicious breast findings requiring biopsy with subsequent diagnosis of NS. The time from biopsy to NS diagnosis was calculated. Histology, grade, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, T category, and N category were recorded. Biopsy guidance method, needle gauge, and number of passes were reviewed in addition to the mammographic and sonographic features of the primary tumors and the NS., Results: Eight cases of NS were identified in 4010 patients. The mean time from biopsy to NS diagnosis was 60.8 days. The most frequent histology was invasive ductal carcinoma (7/8). Six cases were grade 3 (75.0%). Five primary breast cancers were ER, PR, and HER2 negative (62.5%). Seven patients underwent biopsy with ultrasound guidance. Multiple-insertion, non-coaxial ultrasound-guided core-needle biopsy was done in 6 cases. Mammographic presentation of NS was focal asymmetry (3/7 cases), mass (1/7), calcifications only (1/7), or occult (2/7). Sonographic presentation of NS was most often a mass (7/8) with irregular shape (5/7) and without circumscribed margins (6/7) and was occult in 1 case (1/8). NS distribution was subdermal and intradermal., Conclusion: High-grade, triple-negative breast cancers and multiple-insertion, non-coaxial biopsies may be risk factors for NS. NS should be suspected on the basis of the superficial and linear pattern of disease progression in these patients.

Objective: Studies show that health care tailored to patient preferences results in significant improvements in physician performance, patient satisfaction, and health outcomes. Limited information in the literature exists on the factors driving patient preferences for establishing care at specific breast imaging centers. In this study, we identified factors that drive cohort preferences in the selection of a breast imaging center., Materials and Methods: An 18-question survey was deployed in a large metropolitan area to gather information on patient demographics and preferences for breast imaging center location and radiologist training level. Cluster analysis and the K-means method were used to classify patients into groups on the basis of their answers about preference. Clusters were tested for significant differences by location, reason for visit, age, education, marital status, ethnicity, insurance, history of cancer, and income., Results: A total of 1682 survey responses (18% of total patient visits) were obtained. Four distinct cohorts (comprising 876 patients) based on patient care preferences were identified: convenience optimizers (n = 109, 12.4%), ambivalent patients (n = 237, 27.1%), medical center seekers (n = 324, 37.0%), and expertise seekers (n = 206, 23.5%). Each cohort showed distinct preferences for imaging center location and radiologist training. Cohorts were differentiated on the basis of patient education level, ethnicity, and patient cancer history. Across the cohorts, there were no significant differences in age, marital status, insurance, income, and other demographic factors., Conclusion: Patient preferences for breast imaging care and location vary and are correlated with specific demographic characteristics. An understanding of these population characteristics can shape organizational strategies for improving patient-centered care and outcomes.

The Breast Imaging Reporting and Data System (BI-RADS ® ) is a standardized system of reporting breast pathology as seen on mammogram, ultrasound, and magnetic resonance imaging. It encourages consistency between reports and facilitates clear communication between the radiologist and other physicians by providing a lexicon of descriptors, a reporting structure that relates assessment categories to management recommendations, and a framework for data collection and auditing. This article highlights the changes made to the BI-RADS ® atlas 5th edition by comparison with its predecessor, provide a useful resource for a radiologist attempting to review the recent changes to the new edition, and serve as a quick reference to those who have previously become familiar with the material., (Copyright © 2017 Éditions françaises de radiologie. All rights reserved.)

Objective: The purpose of this article is to describe the feasibility and safety of a multidisciplinary approach to imaging-guided axillary staging that facilitates personalized, less invasive surgical management of the axilla through targeted axillary dissection in patients with biopsy-proven nodal metastasis undergoing neoadjuvant chemotherapy., Conclusion: Axillary nodal status, critical in breast cancer staging, affects prognosis and treatment. As the paradigm shifts toward minimally invasive therapy, a clip marker is placed in the biopsied metastatic node for patients with N1-N2 disease undergoing neoadjuvant chemotherapy to facilitate targeted axillary dissection of the clipped node. This node is typically localized with a radioactive seed at sentinel lymph node dissection to determine whether further axillary surgery is warranted.

Purpose: Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone., Methods: A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND)., Results: Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7)., Conclusion: Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy., (© 2016 by American Society of Clinical Oncology.)

Computer-aided diagnosis (CAD) systems are software programs that use algorithms to find patterns associated with breast cancer on breast magnetic resonance imaging (MRI). The most commonly used CAD systems in the USA are CADstream (CS) (Merge Healthcare Inc., Chicago, IL) and DynaCAD for Breast (DC) (Invivo, Gainesville, FL). Our primary objective in this study was to compare the CS and DC breast MRI CAD systems for diagnostic accuracy and postprocessed image quality. Our secondary objective was to compare the evaluation times of radiologists using each system. Three radiologists evaluated 30 biopsy-proven malignant lesions and 29 benign lesions on CS and DC and rated the lesions' malignancy status using the Breast Imaging Reporting and Data System. Image quality was ranked on a 0-5 scale, and mean reading times were also recorded. CS detected 70 % of the malignant and 32 % of the benign lesions while DC detected 81 % of the malignant lesions and 34 % of the benign lesions. Analysis of the area under the receiver operating characteristic curve revealed that the difference in diagnostic performance was not statistically significant. On image quality scores, CS had significantly higher volume rendering (VR) (p < 0.0001) and motion correction (MC) scores (p < 0.0001). There were no statistically significant differences in the remaining image quality scores. Differences in evaluation times between DC and CS were also not statistically significant. We conclude that both CS and DC perform similarly in aiding detection of breast cancer on MRI. MRI CAD selection will likely be based on other factors, such as user interface and image quality preferences, including MC and VR.

Rationale and Objectives: The purpose of this study was to review the imaging findings associated with lobular carcinoma in situ (LCIS) of the breast with clinical and pathological correlation., Materials and Methods: A database search of patients treated at our institution from 2002 to 2011 identified 26 patients with LCIS associated with an imaging abnormality that had imaging available for review. LCIS was diagnosed by core-needle or excision biopsy. Patients subsequently underwent excisional biopsy, mastectomy, or clinical follow-up. Patients' mammography, ultrasonography (US), and magnetic resonance imaging (MRI) images were reviewed using the American College of Radiology Breast Imaging Reporting and Data System lexicon together with relevant clinical and pathology data., Results: The 26 patients had 31 imaging lesions that yielded a histological diagnosis of LCIS by image-guided core-needle biopsy (n = 29) or excision biopsy (n = 2). Twenty-eight of 31 (90%) lesions yielding LCIS had a mammographic abnormality, 3/20 (15%) lesions had a US abnormality, and 6/7 (86%) had an abnormality on contrast-enhanced MRI. Calcifications were the most common mammographic finding, seen in 25/31 (80%) lesions. All three lesions seen on US were masses; the majority was irregular, hypoechoic, avascular, and had posterior shadowing. Non-mass-like enhancement was seen in five (71%) lesions with an MRI abnormality. Two (7%) patients developed subsequent malignancy at follow-up., Conclusion: LCIS can have associated imaging abnormalities, most commonly grouped amorphous calcifications on mammography, a shadowing, avascular, irregular, hypoechoic mass on US, or heterogeneous non-mass-like enhancement with persistent enhancement kinetics on MRI., (Copyright © 2013 AUR. Published by Elsevier Inc. All rights reserved.)

Objective: This purpose of this study is to describe the imaging findings in patients who presented with a diagnosis of primary breast sarcoma., Materials and Methods: A search was performed of the pathology database at a single institution for patients with a histopathologic diagnosis of primary breast sarcoma or pure sarcomatoid carcinoma and who underwent preoperative mammography, sonography, or MRI. Patients with malignant phyllodes tumors were excluded. The imaging studies were retrospectively reviewed using the American College of Radiology BI-RADS lexicon. We documented clinical presentation, histopathologic characteristics, axillary nodal status, and the presence of distant metastases., Results: Twenty-four women were included in the study; their mean age was 56 years (range, 21-86 years), and the mean tumor size was 6.1 cm (range, 0.9-15 cm). Only one tumor was identified in each patient. The predominant mammographic finding was a noncalcified oval mass with indistinct (9/14 [64%]) margins. Sonography most commonly revealed an oval (19/22 [86%]) solid mass with indistinct margins (17/22 [77%]). The masses were frequently hypoechoic (18/21 [86%]) and hypervascular (17/20 [85%]) and had posterior acoustic enhancement (13/21 [62%]). MRI showed a round or oval T2-hyperintense mass with irregular margins in four of five (80%) patients, and inhomogeneous enhancement was most common (3/4 [75%])., Conclusion: Primary breast sarcoma has imaging features that are not typically seen in infiltrating ductal carcinoma. A large oval hypervascular mass with indistinct margins should raise the suspicion for a primary breast sarcoma and prompt biopsy.

Objective: Early detection of breast cancer is directly related to the radiologist's ability to detect abnormalities visible only on mammograms. Artifacts on mammograms reduce image quality and may present clinical and technical difficulties for the radiologist, mammography technologist, medical physicist, and equipment service personnel., Conclusion: In this article, we will illustrate the appearance of artifacts in full field digital mammography, review the causes of these artifacts, and discuss methods to eliminate artifacts in digital mammography.

Objective: The purpose of this essay is to describe the imaging characteristics of adenomyoepithelial tumors of the breast., Conclusion: Adenomyoepithelial tumors of the breast are rare, and most are benign. The predominant mammographic and ultrasound feature is an irregular mass with suspicious imaging findings. This uncommon condition should be included in the differential diagnosis of noncalcified masses found on mammograms and of solid masses with associated hypervascularity on ultrasound images. Biopsy is necessary for histologic evaluation, and the management is surgical excision.

Rationale and Objectives: American College of Radiology guidelines suggest that digital screening mammographic images should be viewed at the full resolution at which they were acquired. This slows interpretation speed. The aim of this study was to examine the effect of various levels of zooming on the detection and conspicuity of microcalcifications., Materials and Methods: Six radiologists viewed 40 mammographic images five times in different random orders using five different levels of zooming: full resolution (100%) and 30%, 61%, 88%, and 126% of that size. Thirty-three images contained microcalcifications varying in subtlety, all associated with breast cancer. The clusters were circled. Seven images contained no malignant calcifications but also had randomly placed circles. The radiologists graded the presence or absence and visual conspicuity of any calcifications compared to calcifications in a reference image. They also counted the microcalcifications., Results: The radiologists saw the microcalcifications in 94% of the images at 30% size and in either 99% or 100% of the other tested levels of zooming. Conspicuity ratings were worst for the 30% size and fairly similar for the others. Using the 30% size, two radiologists failed to see the microcalcifications on either the craniocaudal or mediolateral oblique view taken from one patient. Interobserver agreement regarding the number of calcifications was lowest for the 30% images and second lowest for the 100% images., Conclusions: Images at 30% size should not be relied on alone for systematic scanning for microcalcifications. The other four levels of magnification all performed well enough to warrant further testing.

Aplidin is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulation of Rac1 by transfection of small interfering RNA (siRNA) duplexes or the use of a specific Rac1 inhibitor decreased Aplidin-induced JNK activation and cytotoxicity. Our results show that Aplidin induces apoptosis by increasing the GSSG/GSH ratio, a necessary step for induction of oxidative stress and sustained JNK activation through Rac1 activation and MKP-1 downregulation.