Diffusion Tensor Imaging for Characterizing Changes in Triple-Negative Breast Cancer During Neoadjuvant Systemic Therapy.

BACKGROUND: Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST). PURPOSE: To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST. STUDY TYPE: Prospective. POPULATION: Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR). FIELD STRENGTH/SEQUENCE: 3.0 T/reduced field of view single-shot echo-planar DTI sequence. ASSESSMENT: Three MRI scans were acquired longitudinally (pre-treatment, after 2 cycles of NAST, and after 4 cycles of NAST). Eleven histogram features were extracted from DTI parameter maps of tumors, a peritumoral region (PTR), and FGT in the ipsilateral breast. DTI parameters included apparent diffusion coefficients and relative diffusion anisotropies. pCR status was determined at surgery. STATISTICAL TESTS: Longitudinal changes of DTI features were tested for discrimination of pCR using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC). A P value <0.05 was considered statistically significant. RESULTS: 47% of patients (40/86) had pCR. DTI parameters assessed after 2 and 4 cycles of NAST were significantly different between pCR and non-pCR patients when compared between tumors, PTRs, and FGTs. The median surface/average anisotropy of the PTR, measured after 2 and 4 cycles of NAST, increased in pCR patients and decreased in non-pCR patients (AUC: 0.78; 0.027 ± 0.043 vs. -0.017 ± 0.042 mm2 /s). DATA CONCLUSION: Quantitative DTI features from breast tumors and the peritumoral tissue may be useful for predicting the response to NAST in TNBC. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

Challenging Contrast-Enhanced Mammography-Guided Biopsies: Practical Approach Using Real-Time Multimodality Imaging and a Proposed Procedural Algorithm.

Contrast-enhanced mammography (CEM) is an emerging functional breast imaging technique that entails the acquisition of dual-energy digital mammographic images after IV administration of iodine-based contrast material. CEM-guided biopsy technology was introduced in 2019 and approved by the U.S. FDA in 2020. This technology's availability enables direct sampling of suspicious enhancement seen only on or predominantly on recombined CEM images and addresses a major obstacle to the clinical implementation of CEM technology. The literature describing clinical indications and procedural techniques of CEM-guided biopsy is scarce. This article describes our initial experience in performing challenging CEM-guided biopsies and proposes a step-by-step procedural algorithm designed to proactively address anticipated technical difficulties and thereby increase the likelihood of achieving successful targeting.

Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial.

BACKGROUND: Neoadjuvant systemic therapy (NST) for triple-negative breast cancer and HER2-positive breast cancer yields a pathological complete response in approximately 60% of patients. A pathological complete response to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB). We evaluated radiotherapy alone, without breast surgery, in patients with early-stage triple-negative breast cancer or HER2-positive breast cancer treated with NST who had an image-guided VACB-determined pathological complete response. METHODS: This multicentre, single-arm, phase 2 trial was done in seven centres in the USA. Women aged 40 years or older who were not pregnant with unicentric cT1-2N0-1M0 triple-negative breast cancer or HER2-positive breast cancer and a residual breast lesion less than 2 cm on imaging after clinically standard NST were eligible for inclusion. Patients had one biopsy (minimum of 12 cores) obtained by 9G image-guided VACB of the tumour bed. If no invasive or in-situ disease was identified, breast surgery was omitted, and patients underwent standard whole-breast radiotherapy (40 Gy in 15 fractions or 50 Gy in 25 fractions) plus a boost (14 Gy in seven fractions). The primary outcome was the biopsy-confirmed ipsilateral breast tumour recurrence rate determined using the Kaplan-Meier method assessed in the per-protocol population. Safety was assessed in all patients who received VACB. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02945579. FINDINGS: Between March 6, 2017, and Nov 9, 2021, 58 patients consented to participate; however, four (7%) did not meet final inclusion criteria and four (7%) withdrew consent. 50 patients were enrolled and underwent VACB following NST. The median age of the enrolled patients was 62 years (IQR 55-77); 21 (42%) patients had triple-negative breast cancer and 29 (58%) had HER2-positive breast cancer. VACB identified a pathological complete response in 31 patients (62% [95% CI 47·2-75·4). At a median follow-up of 26·4 months (IQR 15·2-39·6), no ipsilateral breast tumour recurrences occurred in these 31 patients. No serious biopsy-related adverse events or treatment-related deaths occurred. INTERPRETATION: Eliminating breast surgery in highly selected patients with an image-guided VACB-determined pathological complete response following NST is feasible with promising early results; however, additional prospective clinical trials evaluating this approach are needed. FUNDING: US National Cancer Institute (National Institutes of Health).

Quantitative Apparent Diffusion Coefficients From Peritumoral Regions as Early Predictors of Response to Neoadjuvant Systemic Therapy in Triple-Negative Breast Cancer.

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 mm2 /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.

Early ultrasound evaluation identifies excellent responders to neoadjuvant systemic therapy among patients with triple-negative breast cancer.

BACKGROUND: Heterogeneity exists in the response of triple-negative breast cancer (TNBC) to standard anthracycline (AC)/taxane-based neoadjuvant systemic therapy (NAST), with 40% to 50% of patients having a pathologic complete response (pCR) to therapy. Early assessment of the imaging response during NAST may identify a subset of TNBCs that are likely to have a pCR upon completion of treatment. The authors aimed to evaluate the performance of early ultrasound (US) after 2 cycles of neoadjuvant NAST in identifying excellent responders to NAST among patients with TNBC. METHODS: Two hundred fifteen patients with TNBC were enrolled in the ongoing ARTEMIS (A Robust TNBC Evaluation Framework to Improve Survival) clinical trial. The patients were divided into a discovery cohort (n = 107) and a validation cohort (n = 108). A receiver operating characteristic analysis with 95% confidence intervals (CIs) and a multivariate logistic regression analysis were performed to model the probability of a pCR on the basis of the tumor volume reduction (TVR) percentage by US from the baseline to after 2 cycles of AC. RESULTS: Overall, 39.3% of the patients (42 of 107) achieved a pCR. A positive predictive value (PPV) analysis identified a cutoff point of 80% TVR after 2 cycles; the pCR rate was 77% (17 of 22) in patients with a TVR ≥ 80%, and the area under the curve (AUC) was 0.84 (95% CI, 0.77-0.92; P < .0001). In the validation cohort, the pCR rate was 44%. The PPV for pCR with a TVR ≥ 80% after 2 cycles was 76% (95% CI, 55%-91%), and the AUC was 0.79 (95% CI, 0.70-0.87; P < .0001). CONCLUSIONS: The TVR percentage by US evaluation after 2 cycles of NAST may be a cost-effective early imaging biomarker for a pCR to AC/taxane-based NAST.

Tumor necrosis by pretreatment breast MRI: association with neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

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.

Mean Apparent Diffusion Coefficient Is a Sufficient Conventional Diffusion-weighted MRI Metric to Improve Breast MRI Diagnostic Performance: Results from the ECOG-ACRIN Cancer Research Group A6702 Diffusion Imaging Trial.

Background The Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Cancer Research Group A6702 multicenter trial helped confirm the potential of diffusion-weighted MRI for improving differential diagnosis of suspicious breast abnormalities and reducing unnecessary biopsies. A prespecified secondary objective was to explore the relative value of different approaches for quantitative assessment of lesions at diffusion-weighted MRI. Purpose To determine whether alternate calculations of apparent diffusion coefficient (ADC) can help further improve diagnostic performance versus mean ADC values alone for analysis of suspicious breast lesions at MRI. Materials and Methods This prospective trial (ClinicalTrials.gov identifier: NCT02022579) enrolled consecutive women (from March 2014 to April 2015) with a Breast Imaging Reporting and Data System category of 3, 4, or 5 at breast MRI. All study participants underwent standardized diffusion-weighted MRI (b = 0, 100, 600, and 800 sec/mm2). Centralized ADC measures were performed, including manually drawn whole-lesion and hotspot regions of interest, histogram metrics, normalized ADC, and variable b-value combinations. Diagnostic performance was estimated by using the area under the receiver operating characteristic curve (AUC). Reduction in biopsy rate (maintaining 100% sensitivity) was estimated according to thresholds for each ADC metric. Results Among 107 enrolled women, 81 lesions with outcomes (28 malignant and 53 benign) in 67 women (median age, 49 years; interquartile range, 41-60 years) were analyzed. Among ADC metrics tested, none improved diagnostic performance versus standard mean ADC (AUC, 0.59-0.79 vs AUC, 0.75; P = .02-.84), and maximum ADC had worse performance (AUC, 0.52; P < .001). The 25th-percentile ADC metric provided the best performance (AUC, 0.79; 95% CI: 0.70, 0.88), and a threshold using median ADC provided the greatest reduction in biopsy rate of 23.9% (95% CI: 14.8, 32.9; 16 of 67 BI-RADS category 4 and 5 lesions). Nonzero minimum b value (100, 600, and 800 sec/mm2) did not improve the AUC (0.74; P = .28), and several combinations of two b values (0 and 600, 100 and 600, 0 and 800, and 100 and 800 sec/mm2; AUC, 0.73-0.76) provided results similar to those seen with calculations of four b values (AUC, 0.75; P = .17-.87). Conclusion Mean apparent diffusion coefficient calculated with a two-b-value acquisition is a simple and sufficient diffusion-weighted MRI metric to augment diagnostic performance of breast MRI compared with more complex approaches to apparent diffusion coefficient measurement. © RSNA, 2020 Online supplemental material is available for this article.

Prospective Registry Trial Assessing the Use of Magnetic Seeds to Locate Clipped Nodes After Neoadjuvant Chemotherapy for Breast Cancer Patients.

BACKGROUND: Targeted axillary dissection (TAD) involves locating and removing both clipped nodes and sentinel nodes for assessment of the axillary response to neoadjuvant chemotherapy (NAC) by clinically node-positive breast cancer patients. Initial reports described radioactive seeds used for localization, which makes the technique difficult to implement in some settings. This trial was performed to determine whether magnetic seeds can be used to locate clipped axillary lymph nodes for removal. METHODS: This prospective registry trial enrolled patients who had biopsy-proven node-positive disease with a clip placed in the node and treatment with NAC. A magnetic seed was placed under ultrasound guidance in the clipped node after NAC. All the patients underwent TAD. RESULTS: Magnetic seeds were placed in 50 patients by 17 breast radiologists. All the patients had successful seed placement at the first attempt (mean time for localization was 6.1 min; range 1-30 min). The final position of the magnetic seed was within the node (n = 44, 88%), in the cortex (n = 3, 6%), less than 3 mm from the node (n = 2, 4%), or by the clip when the node could not be adequately visualized (n = 1, 2%). The magnetic seed was retrieved at surgery from all the patients. In 49 (98%) of the 50 cases, the clip and magnetic seed were retrieved from the same node. Surgeons rated the transcutaneous and intraoperative localization as easy for 43 (86%) of the 50 cases. No device-related adverse events occurred. CONCLUSIONS: Localization and selective removal of clipped nodes can be accomplished safely and effectively using magnetic seeds.

Functional Tumor Volume by Fast Dynamic Contrast-Enhanced MRI for Predicting Neoadjuvant Systemic Therapy Response in Triple-Negative Breast Cancer.

BACKGROUND: Dynamic contrast-enhanced (DCE) MRI is useful for diagnosis and assessment of treatment response in breast cancer. Fast DCE MRI offers a higher sampling rate of contrast enhancement curves in comparison to conventional DCE MRI, potentially characterizing tumor perfusion kinetics more accurately for measurement of functional tumor volume (FTV) as a predictor of treatment response. PURPOSE: To investigate FTV by fast DCE MRI as a predictor of neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC). STUDY TYPE: Prospective. POPULATION/SUBJECTS: Sixty patients with biopsy-confirmed TNBC between December 2016 and September 2020. FIELD STRENGTH/SEQUENCE: A 3.0 T/3D fast spoiled gradient echo-based DCE MRI ASSESSMENT: Patients underwent MRI at baseline and after four cycles (C4) of NAST, followed by definitive surgery. DCE subtraction images were analyzed in consensus by two breast radiologists with 5 (A.H.A.) and 2 (H.S.M.) years of experience. Tumor volumes (TV) were measured on early and late subtractions. Tumors were segmented on 1 and 2.5-minute early phases subtractions and FTV was determined using optimized signal enhancement thresholds. Interpolated enhancement curves from segmented voxels were used to determine optimal early phase timing. STATISTICAL TESTS: Tumor volumes were compared between patients who had a pathologic complete response (pCR) and those who did not using the area under the receiver operating curve (AUC) and Mann-Whitney U test. RESULTS: About 26 of 60 patients (43%) had pCR. FTV at 1 minute after injection at C4 provided the best discrimination between pCR and non-pCR, with AUC (95% confidence interval [CI]) = 0.85 (0.74,0.95) (P < 0.05). The 1-minute timing was optimal for FTV measurements at C4 and for the change between C4 and baseline. TV from the early phase at C4 also yielded a good AUC (95%CI) of 0.82 (0.71,0.93) (P < 0.05). DATA CONCLUSION: FTV and TV measured at 1 minute after injection can predict response to NAST in TNBC. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 4.

Imaging-Based Approach to Axillary Lymph Node Staging and Sentinel Lymph Node Biopsy in Patients With Breast Cancer.

OBJECTIVE. This review provides historical and current data to support the role of imaging-based axillary lymph node staging and sentinel lymph node biopsy as the standard of care for axillary management in women with a diagnosis of breast cancer, before and after neoadjuvant systemic therapy. CONCLUSION. The implications of surgical trials (American College of Surgeons Oncology Group [ACOSOG] Z011 and ACOSOG Z1071) on imaging protocols for the axilla are reviewed, in conjunction with the American Joint Committee on Cancer nodal staging guidelines.

Sonographic features of benign and malignant axillary nodes post-neoadjuvant chemotherapy.

The aim was to determine whether sonographic features of metastatic axillary lymph nodes predict pathologic nodal status post-neoadjuvant chemotherapy (NCT) and help to tailor less invasive surgical management of the axilla. Patients with biopsy-proven cN1 primary breast malignancy who received NCT between January 2011 and December 2014 and had performed ultrasound were included in this study. Sonographic features of biopsy-proven clipped metastatic axillary nodes pre- and post-NCT were retrospectively reviewed by two independent readers. Changes in lymph node shape, fatty hilum status, cortical thickness, and cortical echogenicity were compared in patients with and without nodal pathologic complete response (pCR) using univariate and multivariate logistic regression models. Inter-reader variation was analyzed to determine the reproducibility of data. Of the 195 patients included in the study, 75 (45%) showed nodal pCR and 90 (55%) persistent metastatic disease post-NCT. pCR was significantly more likely in lymph nodes with isoechoic or hypoechoic cortical echogenicity post-NCT, (P = .02), conversion to normal cortical thickness (P = .0001), and oval shape (odds ratio = 0.17, P = .004), compared to lymph nodes with anechoic cortical echogenicity, persistent or diffuse cortical thickening, and irregular shape, respectively. The overall accuracy of sonographic nodal features in the prediction of pCR was 65% (95% CI: 58%-72%). The overall accuracy of sonographic features of biopsy-proven metastatic axillary lymph nodes post-NCT is not sufficiently high to predict pCR of axillary nodal status and thereby should not be solely used in guiding less invasive surgical approaches to the axilla.

Feasibility of fine-needle aspiration for assessing responses to chemotherapy in metastatic nodes marked with clips in breast cancer: A prospective registry study.

BACKGROUND: Clips are often placed to mark axillary nodes with biopsy-confirmed metastases in patients with breast cancer. The evaluation of clipped nodes after chemotherapy can identify patients who have eradication of nodal disease. The goal of this study was to determine whether preoperative fine-needle aspiration (FNA) of clipped nodes after neoadjuvant chemotherapy (NAC) could predict the presence of residual disease. METHODS: This prospective registry study enrolled 50 patients with a clip placed to mark nodes with biopsy-confirmed metastases who had completed NAC. Participants underwent FNA of the clipped node before seed-localized lymph node excision. FNA pathology was compared with surgical pathology. RESULTS: There were 36 patients (72%) with residual disease on surgical pathology: 3 (8%) had a nondiagnostic aspirate, carcinoma was seen in 14 (39%), and 19 (53%) had a false-negative result. The sensitivity of FNA was 42.4%, its specificity was 100%, and its negative predictive value was 40.6%. In a univariate analysis, the odds of a true-positive result increased significantly with the mean initial size of the clipped node (odds ratio [OR], 4.3; P = .004) and the size of the metastatic focus after NAC (OR, 1.3; P = 0.003), whereas normalization of nodes after chemotherapy (OR, 0.1) and a lack of response on ultrasound (OR, 0.11) were associated with a false-negative result (P = .01). CONCLUSIONS: FNA of marked nodes after chemotherapy has a high false-negative rate. This highlights the need for surgical staging of the axilla after NAC to assess the response.

Ductal Carcinoma In Situ and Margins <2 mm: Contemporary Outcomes With Breast Conservation.

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.

Patient Selection for Clinical Trials Eliminating Surgery for HER2-Positive Breast Cancer Treated with Neoadjuvant Systemic Therapy.

BACKGROUND: Patients with epidermal growth factor receptor 2-positive (HER2+) breast cancer and pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) may be candidates for nonoperative clinical trials if residual invasive and in situ disease are eradicated. METHODS: This study analyzed 280 patients with clinical T1-2N0-1 HER2+ breast cancer who underwent NST followed by surgical resection to determine key characteristics of patients with pCR in the breast and lymph nodes compared with those with residual disease. RESULTS: Of the 280 patients, 102 (36.4%) had pCR in the breast and lymph nodes after NST, and 50 patients (17.9%) had residual ductal carcinoma in situ (DCIS) in the breast only. For 129 patients (46.1%), DCIS was present on the pretreatment biopsy, and NST failed to eradicate the DCIS component in 64.3%. Patients with residual disease were more likely to have hormone receptor-positive (HR+) tumors than those with negative tumors (73.4% vs. 50.8%; p < 0.0001). Radiologic response (odds ratio [OR], 5.62; p = 0.002) and HR+ status (OR, 2.56; p < 0.0001) were predictive of residual disease. Combined imaging methods after NST had a sensitivity of 97.1% and a negative predictive value of 70.6% for detection of residual disease. Patients with invasive disease and DCIS shown on the pretreatment core biopsy were less likely than those without DCIS to achieve pCR in the breast (31% vs. 43%; p = 0.038). CONCLUSION: The study results delineate and identify unique characteristics associated with HER2+ breast cancers that are important in selecting patients for inclusion in clinical trials assessing nonoperative management after NST, and the low negative predictive value of imaging mandates image-guided biopsy for selection.

Immunotherapy and the role of imaging.

Significant advances in the genetic and molecular characterization of cancer have led to the development of effective immunotherapies. These therapeutics help the host immune system recognize cancer as foreign, promote the immune system, and relieve the inhibition that allows growth and spread of tumors. Experience with various immunotherapies, particularly the immunomodulatory monoclonal antibody ipilimumab, has demonstrated that unique patterns of response may be encountered that cannot be adequately captured by traditional response criteria, such as the World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST), which have been used primarily with cytotoxic chemotherapies. In response to these observations, several novel response criteria have been developed to evaluate patients who receive immunotherapy, including immune-related response criteria (irRC), immune-related RECIST (irRECIST), and immune RECIST (iRECIST). These criteria are typically used in conjunction with RECIST version 1.1 in the clinical trial setting, because approval of new therapeutics by the US Food and Drug Administration relies on the responses derived from RECIST version 1.1. Finally, a wide variety of immune-related adverse events may affect patients who receive immunotherapy, many of which can be identified on imaging studies such as computed tomography, magnetic resonance imaging, and 2-deoxy-2-(fluorine-18)fluoro-D-glucose-positron emission tomography/computed tomography. In this review, the authors present the role of imaging in the evaluation of patients treated with immunotherapy, including the background and application of irRC, irRECIST, and iRECIST; the imaging of immune-related adverse events; and future directions in advanced imaging of immunotherapy. Cancer 2018;124:2906-22. © 2018 American Cancer Society.

A Clinical Feasibility Trial for Identification of Exceptional Responders in Whom Breast Cancer Surgery Can Be Eliminated Following Neoadjuvant Systemic Therapy.

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.

Biopsy Feasibility Trial for Breast Cancer Pathologic Complete Response Detection after Neoadjuvant Chemotherapy: Imaging Assessment and Correlation Endpoints.

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 Ca2+ 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.

Exploring the Negative Likelihood Ratio and How It Can Be Used to Minimize False-Positives in Breast Imaging.

OBJECTIVE: This article describes the definition and proposed utilization of negative likelihood ratios (NLRs) as statistical parameters in breast imaging. Examples with calculations are provided using BI-RADS category 4 subcategories. CONCLUSION: By auditing individual performance early and often against American College of Radiology benchmark positive predictive value ranges for the BI-RADS category 4 subcategories, and by fully understanding NLRs and their application in breast imaging, radiologists can minimize false-positive findings and unnecessary biopsies.

American College of Radiology-Compliant Short Protocol Breast MRI for High-Risk Breast Cancer Screening: A Prospective Feasibility Study.

OBJECTIVE: The purpose of this study was to assess the feasibility of a short protocol for screening breast MRI that is noninferior to standard-of-care (SOC) MRI in image quality that complies with American College of Radiology accreditation requirements. SUBJECTS AND METHODS: In a prospective feasibility trial, 23 women at high risk underwent both an initial SOC MRI examination that included axial iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) and T1-weighted volume imaging for breast assessment (VIBRANT) dynamic contrast-enhanced sequences and a separate short breast MRI protocol comprising a fast spin-echo (FSE) triple-echo Dixon T2 sequence for T2-weighted imaging and a 3D dual-echo fast spoiled gradient-echo two-point Dixon sequence for dynamic contrast-enhanced imaging from October 1, 2015, through May 2, 2016. Image quality assessment was performed by three radiologists, who scored the images for fat saturation, artifact severity, and quality of normal anatomic structures. Enhancing lesions were evaluated according to BI-RADS MRI features. Quantitative analysis was performed by measuring the signal intensity of anatomic areas in each patient. RESULTS: The mean acquisition time for short-protocol breast MRI was 9.42 minutes and for SOC MRI was 22.09 minutes (p < 0.0001). The mean table times were 13.92 and 35.87 minutes (p < 0.0001). Compared with the FSE triple-echo Dixon T2 short-protocol breast MRI sequence, the IDEAL SOC MRI sequence had significantly worse motion artifact (p < 0.01) and fat saturation (p = 0.04). The other parameters did not differ significantly. Quantitative analysis showed that the FSE triple-echo Dixon T2 sequence had more effective fat saturation and higher tissue contrast. All five lesions were given the same assessments by the readers, and at BI-RADS lesion morphologic ranking, identical high image quality scores were assigned to both the VIBRANT and 3D dual-echo fast spoiled gradient-echo 2-point Dixon sequences. CONCLUSION: Short-protocol breast MRI comprising a T2-weighted sequence and a fast dynamic sequence with less than 10-minute acquisition time is feasible and has image quality at least equivalent to that of an SOC MRI protocol with a > 20-minute mean acquisition time. Larger studies comparing the cancer detection rate, sensitivity, and specificity of each imaging protocol are needed to determine whether short-protocol breast MRI can replace SOC MRI to screen patients at high breast cancer risk.