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.

Multimodality Imaging of Benign and Malignant Diseases of the Nipple-Areolar Complex.

The nipple-areolar complex (NAC), a unique anatomic structure of the breast, encompasses the terminal intramammary ducts and skin appendages. Several benign and malignant diseases can arise within the NAC. As several conditions have overlapping symptoms and imaging findings, understanding the distinctive nipple anatomy, as well as the clinical and imaging features of each NAC disease process, is essential. A multimodality imaging approach is optimal in the presence or absence of clinical symptoms. The authors review the ductal anatomy and anomalies, including congenital abnormalities and nipple retraction. They then discuss the causes of nipple discharge and highlight best practices for the imaging workup of pathologic nipple discharge, a common condition that can pose a diagnostic challenge and may be the presenting symptom of breast cancer. The imaging modalities used to evaluate and differentiate benign conditions (eg, dermatologic conditions, epidermal inclusion cyst, mammary ductal ectasia, periductal mastitis, and nonpuerperal abscess), benign tumors (eg, papilloma, nipple adenoma, and syringomatous tumor of the nipple), and malignant conditions (eg, breast cancer and Paget disease of the breast) are reviewed. Breast MRI is the current preferred imaging modality used to evaluate for NAC involvement by breast cancer and select suitable candidates for nipple-sparing mastectomy. Different biopsy techniques (US -guided biopsy and stereotactic biopsy) for sampling NAC masses and calcifications are described. This multimodality imaging approach ensures an accurate diagnosis, enabling optimal clinical management and patient outcomes. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

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.

Triple-Negative Breast Cancer: Histopathologic Features, Genomics, and Treatment.

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive group of tumors that are defined by the absence of estrogen and progesterone receptors and lack of ERBB2 (formerly HER2 or HER2/neu) overexpression. TNBC accounts for 8%-13% of breast cancers. In addition, it accounts for a higher proportion of breast cancers in younger women compared with those in older women, and it disproportionately affects non-Hispanic Black women. TNBC has high metastatic potential, and the risk of recurrence is highest during the 5 years after it is diagnosed. TNBC exhibits benign morphologic imaging features more frequently than do other breast cancer subtypes. Mammography can be suboptimal for early detection of TNBC owing to factors that include the fast growth of this cancer, increased mammographic density in young women, and lack of the typical features of malignancy at imaging. US is superior to mammography for TNBC detection, but benign-appearing features can lead to misdiagnosis. Breast MRI is the most sensitive modality for TNBC detection. Most cases of TNBC are treated with neoadjuvant chemotherapy, followed by surgery and radiation. MRI is the modality of choice for evaluating the response to neoadjuvant chemotherapy. Survival rates for individuals with TNBC are lower than those for persons with hormone receptor-positive and human epidermal growth factor receptor 2-positive cancers. The 5-year survival rates for patients with localized, regional, and distant disease at diagnosis are 91.3%, 65.8%, and 12.0%, respectively. The early success of immunotherapy has raised hope regarding the development of personalized strategies to treat TNBC. Imaging and tumor biomarkers are likely to play a crucial role in the prediction of TNBC treatment response and TNBC patient survival in the future. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Evaluation of a Surgical Navigation System for Localization and Excision of Nonpalpable Lesions in Breast and Axillary Surgery.

Introduction: Elucent Medical has introduced a novel EnVisio™ Surgical Navigation system which uses SmartClips™ that generate a unique electromagnetic signal triangulated in 3 dimensions for real-time navigation. The purpose of this study was to evaluate the efficacy and feasibility of the EnVisio Surgical Navigation system in localizing and excising nonpalpable lesions in breast and axillary surgery. Methods: This pilot study prospectively examined patients undergoing breast and nodal localization using the EnVisio Surgical Navigation system. SmartClips were placed by designated radiologists using ultrasound (US) or mammographic (MMG) guidance. The technical evaluation focused on successful deployment and subsequent excision of all localized lesions including SmartClips and biopsy clips. Results: Eleven patients underwent localization using 27 SmartClips which included bracketed multifocal disease (n = 4) and clipped lymph node (n = 1). The bracketed cases were each localized with 2 SmartClips. Mammography and ultrasound were used (n = 8 and n = 19, respectively) to place the SmartClips. All 27 devices were successfully deployed within 5 mm of the targeted lesion or biopsy clip. All SmartClip devices were identified and retrieved intraoperatively. No patients required a second operation for margin excision. Conclusion: In a limited sample, the EnVisio Surgical Navigation system was a reliable technology for the localization of breast and axillary lesions planned for surgical excision. Further comparative studies are required to evaluate its efficacy in relation to the other existing localization modalities.

Clinical Outcomes Using Magnetic Seeds as a Non-wire, Non-radioactive Alternative for Localization of Non-palpable Breast Lesions.

BACKGROUND: Nonpalpable breast lesions require precise preoperative localization to facilitate negative margins with breast-conserving therapy. The traditional use of wires has several challenges including patient discomfort, wire migration, and coordination of schedules between radiology and the operating room. Radioactive seed localization overcomes some of these challenges, but radiation safety requirements have limited adoption of this technology. The authors examined their institutional experience with Magseed as an alternative technology for localization and compared outcomes with those of wire and radioactive seed localization. METHODS: An institutional review board (IRB)-approved retrospective study was performed to evaluate patients who underwent excisional biopsy or segmental mastectomy after wire-guided localization (WGL), radioactive seed localization (RSL), or Magseed localization (ML). The clinical and pathologic factors of the three groups were assessed with a negative margin rate as the primary outcome measure. RESULTS: Of the 1835 patients in the study, 825 underwent WGL, 449 underwent RSL, and 561 underwent ML. For the patients with either multiple lesions or a large lesion that required bracketing, multiple localization devices were placed in 31% of the WGL patients, 28% of the RSL patients, and 23% of the ML patients (p = 0.006). Negative margins were achieved in 91% of the WGL patients, 89% of the RSL patients, and 89% of the ML patients (p = 0.4). CONCLUSION: Localization of non-palpable breast lesions using Magseed is a safe and effective alternative to WGL and RSL that overcomes radiation safety limitations and increases radiology and surgery scheduling efficiency.

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.

The Challenging Image-Guided Preoperative Breast Localization: A Modality-Based Approach.

Breast conservation surgery (BCS) is the standard of care for treating patients with early-stage breast cancer and those with locally advanced breast cancer who achieve an excellent response to neoadjuvant chemotherapy. The radiologist is responsible for accurately localizing nonpalpable lesions to facilitate successful BCS. In this article, we present a practical modality-based guide on approaching challenging pre-operative localizations and incorporate examples of challenging localizations performed under sonographic, mammographic, and MRI guidance, as well as under multiple modalities. Aspects of preprocedure planning, modality selection, patient communication, and procedural and positional techniques are highlighted. Clip and device migration is also considered. Further, an overview is provided of the most widely used wire and nonwire localization devices in the United States. Accurate pre-operative localization of breast lesions is essential to achieve successful surgical outcomes. Certain modality-based techniques can be adopted to successfully complete challenging cases.

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.

Benign Breast Intraductal Papillomas Without Atypia at Core Needle Biopsies: Is Surgical Excision Necessary?

PURPOSE: The aim of this study was to determine the upgrade rate of image-guided core needle biopsy (CNB)-proven benign breast intraductal papillomas (IDPs) without atypia to high-risk benign lesions or malignancy after surgical excision. METHODS: A retrospective database search at a single institution identified 102 adult female patients with benign breast IDPs without atypia diagnosed on imaging-guided CNBs who subsequently had surgical excisions between 2011 and 2016. Patient characteristics, imaging features, biopsy techniques, and the pathology reports from imaging-guided CNBs and subsequent surgical excisions were reviewed. The upgrade rate to malignancies or high-risk benign lesions was determined at the patient level. RESULTS: The upgrade rate to malignancy was 2.9% (3/102), including two cases of ductal carcinoma in situ (DCIS) and one case of microinvasive (< 1 mm) ductal carcinoma arising from DCIS. The upgrade rate to high-risk benign lesions was 7.8% (8/102), with seven cases of atypical ductal hyperplasia and one case of atypical lobular hyperplasia. A personal history of breast cancer and a larger mean lesion size were significantly associated with an upgrade to malignancy (p < 0.05). CONCLUSIONS: The management of benign breast IDPs without atypia detected on imaging-guided CNBs is controversial. Our results suggest risk stratification is important in approaching these patients. Although surgical excision should be considered for all benign breast IDPs without atypia, observation with serial imaging may be appropriate in selected low-risk patients. This approach will save many women from surgeries and decrease the cost of medical care.

Li-Fraumeni Syndrome and Whole-Body MRI Screening: Screening Guidelines, Imaging Features, and Impact on Patient Management.

OBJECTIVE: Li-Fraumeni syndrome (LFS) is a rare autosomal-dominant inherited syndrome containing a germline mutation in the TP53 gene, which predisposes to oncogenesis. Leukemia and tumors of the brain, soft tissues, breasts, adrenal glands, and bone are the most common cancers associated with this syndrome. Patients with LFS are very susceptible to radiation, therefore the use of whole-body MRI is recommended for regular cancer screening. It is important to recognize the common tumors associated with LFS on MRI, and it is also important to be aware of the high rate of false-positive lesions. CONCLUSION: Whole-body MRI is useful for the detection of cancer in patients who come for regular screening; however, it is associated with pitfalls about which the radiologist must remain aware.

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.

Clinical Management of Mucocele-Like Lesions of the Breast with Limited or no Epithelial Atypia on Core Biopsy: Experience from Two Institutions.

PURPOSE: Mucocele-like lesions of the breast identified on core biopsy are rare high-risk lesions associated with variable upgrade rates to carcinoma on excision. We aimed to identify the clinicoradiopathological features that can help optimize management of this lesion. METHODS: We evaluated 50 mucocele-like lesions identified on core biopsies from two institutions, including 36 with no atypia and 14 with limited atypia. Outcome data from excision or clinicoradiological follow-up were reviewed with core biopsy results. RESULTS: Radiological targets were calcifications in 74% of cases, calcifications with associated mass or density in 16%, and mass in 10%. One of the 16 excised lesions without atypia on core biopsy, which was a mass lesion, was upgraded to mucinous carcinoma on excision. Of the 12 excised lesions with limited atypia, none were upgraded on excision. Among the lesions not excised, 20 without atypia had a median follow-up of 61 months, and 2 with limited atypia had follow-up of 97 and 109 months. None of these 22 patients had new development of their lesions on follow-up. The upgrade rate was 2% in our entire cohort, 3% for lesions without atypia, and 0% for lesions with limited atypia. CONCLUSIONS: Clinicoradiological surveillance can be appropriate when a mucocele-like lesion without atypia is identified on core biopsy for a non-mass lesion with pathological-radiological concordance. For mucocele-like lesions with limited atypia, a nonsurgical approach could be considered if the atypia by itself does not warrant excision. The latter recommendation requires careful clinicopathological correlation and support from additional studies.

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.