Surgeon and Radiologist Evaluation of Electromagnetic Chip Localization for Benign and Malignant Breast Lesions.

BACKGROUND: SmartClipTM is a food and drug administration-approved, electromagnetic chip (EMC) localization system that provides three-dimensional navigation for the excision of soft tissue lesions. The purpose of this study was to analyze the accuracy and feasibility of EMC radiologic and surgical localization for benign and malignant breast lesions. PATIENTS AND METHODS: An institutional review board-approved, single institution, prospective study from October 2020 to September 2022 of 38 women undergoing breast conserving surgery with EMC localization of a single lesion > 5 mm on mammogram (MMG) or ultrasound (US) imaging. Surveys from performing breast radiologists and breast surgeons were collected after image-guided localization and surgical excision. RESULTS: Seventy-six survey responses from nine radiologists and four surgeons were received. The deployment needle and EMC were highly visible in 86.8% and 76.3% of procedures, respectively. There was no difficulty in deployment for 92.1% of procedures. The EMC was in the correct location on postdeployment MMG in 97.4% of cases. Three instances of EMC migration occurred, one 1 cm from target lesion. The targeted mass and EMC were within the surgical specimen in 97.4% of cases. On specimen radiograph, 39.5% of the EMCs were 0-1 mm from the center of the target lesion, 18.4% were within 2-4 mm, and 23.7% were within 5-10 mm. Mean operating room time for all cases was 65 min. One case required US to localize the target due to console malfunction. CONCLUSION: There was successful EMC deployment by radiologists with accurate visualization and successful surgical excision in most cases. The EnVisioTM SmartClipTM system is a reproducible and accurate localization method for benign and malignant breast lesions.

Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial.

Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID: NCT02779855 ). Patients with stage 2-3 TNBC received five intratumoral T-VEC injections with paclitaxel followed by doxorubicin and cyclophosphamide and surgery to assess residual cancer burden index (RCB). The primary end point was RCB0 rate. Secondary end points were RCB0-1 rate, recurrence rate, toxicity and immune correlates. Thirty-seven patients were evaluated. Common T-VEC toxicities were fevers, chills, headache, fatigue and injection site pain. NAC toxicities were as expected. Four thromboembolic events occurred. The primary end point was met with an estimated RCB0 rate = 45.9% and RCB0-1 descriptive rate = 65%. The 2-year disease-free rate is equal to 89% with no recurrences in RCB0-1 patients. Immune activation during treatment correlated with response. T-VEC plus NAC in TNBC may increase RCB0-1 rates. These results support continued investigation of T-VEC plus NAC for TNBC.

MRI Response to Pre-operative Stereotactic Ablative Body Radiotherapy (SABR) in Early Stage ER/PR+ HER2- Breast Cancer correlates with Surgical Pathology Tumor Bed Cellularity.

OBJECTIVE: This study evaluates breast MRI response of ER/PR+ HER2- breast tumors to pre-operative SABR with pathologic response correlation. METHODS: Women enrolled in a phase 2 single institution trial of SABR for ER/PR+ HER2- breast cancer were retrospectively evaluated for radiologic-pathologic correlation of tumor response. These patients underwent baseline breast MRI, SABR (28.5 Gy in 3 fractions), follow-up MRI 5 to 6 weeks post-SABR, and lumpectomy. Tumor size and BI-RADS descriptors on pre and post-SABR breast MRIs were compared to determine correlation with surgical specimen % tumor cellularity (%TC). Reported MRI tumor dimensions were used to calculate percent cubic volume remaining (%VR). Partial MRI response was defined as a BI-RADs descriptor change or %VR ≤ 70%, while partial pathologic response (pPR) was defined as %TC ≤ 70%. RESULTS: Nineteen patients completed the trial, and %TC ranged 10% to 80%. For BI-RADS descriptor analysis, 12 of 19 (63%) showed change in lesion or kinetic enhancement descriptors post-SABR. This was associated with lower %TC (29% vs. 47%, P = .042). BI-RADS descriptor change analysis also demonstrated high PPV (100%) and specificity (100%) for predicting pPR to treatment (sensitivity 71%, accuracy 74%), but low NPV (29%). MRI %VR demonstrated strong linear correlation with %TC (R = 0.70, P < .001, Pearson's Correlation) and high accuracy (89%) for predicting pPR (sensitivity 88%, specificity 100%, PPV 100%, and NPV 50%). CONCLUSION: Evaluating breast cancer response on MRI using %VR after pre-operative SABR treatment can help identify patients benefiting the most from neoadjuvant radiation treatment of their ER/PR+ HER2- tumors, a group in which pCR to neoadjuvant therapy is rare.

Quantitative Changes in Intratumoral Habitats on MRI Correlate With Pathologic Response in Early-stage ER/PR+ HER2- Breast Cancer Treated With Preoperative Stereotactic Ablative Body Radiotherapy.

Objective: To quantitatively evaluate intratumoral habitats on dynamic contrast-enhanced (DCE) breast MRI to predict pathologic breast cancer response to stereotactic ablative body radiotherapy (SABR). Methods: Participants underwent SABR treatment (28.5 Gy x3), baseline and post-SABR MRI, and breast-conserving surgery for ER/PR+ HER2- breast cancer. MRI analysis was performed on DCE T1-weighted images. MRI voxels were assigned eight habitats based on high (H) or low (L) maximum enhancement and the sequentially numbered dynamic sequence of maximum enhancement (H1-4, L1-4). MRI response was analyzed by percent tumor volume remaining (%VR = volume post-SABR/volume pre-SABR), and percent habitat makeup (%HM of habitat X = habitat X voxels/total voxels in the segmented volume). These were correlated with percent tumor bed cellularity (%TC) for pathologic response. Results: Sixteen patients completed the trial. The %TC ranged 20%-80%. MRI %VR demonstrated strong correlations with %TC (Pearson R = 0.7-0.89). Pre-SABR tumor %HMs differed significantly from whole breasts (P = 0.005 to <0.00001). Post-SABR %HM of tumor habitat H4 demonstrated the largest change, increasing 13% (P = 0.039). Conversely, combined %HM for H1-3 decreased 17% (P = 0.006). This change correlated with %TC (P < 0.00001) and distinguished pathologic partial responders (≤70 %TC) from nonresponders with 94% accuracy, 93% sensitivity, 100% specificity, 100% positive predictive value, and 67% negative predictive value. Conclusion: In patients undergoing preoperative SABR treatment for ER/PR+ HER2- breast cancer, quantitative MRI habitat analysis of %VR and %HM change correlates with pathologic response.

A Phase I Trial of Talimogene Laherparepvec in Combination with Neoadjuvant Chemotherapy for the Treatment of Nonmetastatic Triple-Negative Breast Cancer.

PURPOSE: Talimogene laherparepvec (TVEC) is an oncolytic herpes simplex 1 virus approved for treatment of melanoma. We hypothesized intratumoral TVEC may enhance response to neoadjuvant chemotherapy (NAC). This article reports the results of a trial combining NAC with TVEC for triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Patients with stage II-III TNBC enrolled in a 3+3 phase I trial (NCT02779855) of two TVEC dose levels [DL; DL 1 = 106 plaque-forming units (PFU) × 5 doses; DL 2 = 106 PFUs first dose, then 108 PFUs × 4 doses] on weeks 1, 4, 6, 8, and 10 plus weekly paclitaxel (80 mg/m2) for 12 weeks, followed by doxorubicin/cyclophosphamide (60/600 mg/m2) every 2 weeks for 8 weeks. Postoperative response assessment using residual cancer burden (RCB) was performed. Primary endpoints were safety and MTD. Secondary endpoints were RCB0 rate and immune correlates. Dose-limiting toxicity (DLT) rule was grade 3-5 adverse events due to TVEC during first 5 weeks. RESULTS: Nine patients [DL 1 (n = 3); DL 2 (n = 6)] were enrolled. Six had stage II disease, and 3 had stage III (6 clinically N+). No DLTs occurred, and MTD was DL 2. Most common toxicities with TVEC were fever (n = 8), chills (n = 3), hematomas (n = 3), and injection site pain (n = 3). Thromboembolic events (n = 2) and bradycardia (n = 1) occurred during or after NAC. Five patients (55%) achieved RCB0, 2 had RCB1 (22%), and 2 had RCB2 (22%). CONCLUSIONS: The addition of TVEC to NAC was feasible at the approved dose, with manageable toxicity. The complete response rate was 55%.

Specialized Second Opinion Review of Breast MRI Impacts Management and Increases Cancer Detection.

OBJECTIVE: The aim of our study is to determine MRI review discrepancy frequency and the subsequent impact on patient management for patients pursuing breast imaging second opinions. METHODS: A retrospective chart review was conducted on 1,000 consecutive patients with second opinion radiology interpretations performed by subspecialty-trained breast radiologists at a dedicated cancer center July 1 through December 31, 2016. Of these, 205 included review of outside breast MRI. Outside imaging reports were compared with second opinion reports to categorize breast MRI review discrepancies. These included relevant BI-RADS category changes or identification of additional extent of disease >4 cm. The discrepancy frequency, relevant alterations in patient management, and incremental cancer detection were measured. Statistical analyses were performed using Fisher's exact test. RESULTS: Discrepant second opinion breast MRI review was seen in 36 of 205 patients (18%). Additional cancer was detected through image-guided biopsy in 3 of these 36 patients and through excision in 2 (5 of 205, 2%). Additionally, five biopsies yielded high-risk pathologic results without upstage on excision. Findings suspicious for additional extent of disease >4 cm were noted in five patients (2%) treated with mastectomies. Finally, five patients had BI-RADS category downgrades. Ultimately, completion of second opinion MRI review recommendations resulted in altered management in 10% of patients (20 of 205). The absence of prior imaging studies for comparison was associated with increased discrepancy frequency (P = .005). CONCLUSION: Second opinion breast MRI review by subspecialized breast imaging radiologists increases cancer detection and results in clinically relevant changes in patient management.

SAVI SCOUT® localization of breast lesions as a practical alternative to wires: Outcomes and suggestions for trouble-shooting.

OBJECTIVE: The purpose of our study was to determine the frequency of successful SAVI SCOUT® localizations, to identify the factors contributing to unsuccessful procedures, and to provide a problem-solving algorithm to address those factors. SUBJECTS AND METHODS: This retrospective study was performed following IRB approval. We included all consecutive patients with SCOUT® reflector placement performed at a single tertiary-care cancer center. Each case was reviewed and the following data were recorded: patient age, breast density, localization target, imaging modality used for guidance, post procedure mammogram reflector to skin and reflector to target distances, presence of the reflector in the specimen radiograph, excisional biopsy pathology and any procedure complications. RESULTS: In 129 women, 152 SAVI SCOUT® reflectors were placed. Most patients had only 1 reflector placed, but 19 (15%) women had multiple reflectors placed for the purposes of bracketing, multiple excisions in 1 breast, bilateral excisions, or any combination thereof. The most common target was a mass (65%) and the most common modality for guidance was ultrasound (73%). SAVI SCOUT® localization was successful in 97%of reflectors, including 89% of reflectors targeting axillary lymph nodes. The most common failure encountered was the inability to obtain a signal in the radiology suite, due to (1) excessive target depth for the radiology suite handpiece and console, (2) obscuration by a hematoma, or (3) faulty reflector. No post-operative complications occurred. CONCLUSION: The SAVI SCOUT® surgical guidance system is an accurate and reliable method for localization of non-palpable breast lesions, bracketing, and axillary lymph nodes.

2-D and 3-D Ultrasound for Tumor Volume Analysis: A Prospective Study.

Ultrasound (US) allows real-time tumor assessment. We evaluated the volumetric limits of 2-D and 3-D US, compared with magnetic resonance imaging (MRI), with a prospective institutional review board-approved clinical evaluation of US-to-MRI volumetric correlation. US images of pre- and post-neoadjuvant breast cancers were obtained. Volume discrepancy was evaluated with the non-parametric Wilcoxon signed-rank test. Expected inter-observer variability <14% was evaluated as relative paired difference (RPD); clinical relevance was gauged with the volumetric standard error of the mean (SEM). For 42 patients, 133 of 170 US examinations were evaluable. For tumors ≤20 cm3, both highly correlated to MRI with RPD within inter-observer variability and Pearson's correlation up to 0.86 (0.80 before and 0.86 after neoadjuvant chemotherapy, respectively). Lesions 20-40 cm3 had US-to-MRI discrepancy within inter-observer variability for 2-D (RPD: 13%), but not 3-D (RPD: 27%) US (SEM: 1.47 cm3 for 2-D, SEM: 2.28 cm3 for 3-D), suggesting clinical utility. Tumors >40 cm3 correlated poorly. Tumor volumes ≤20 cm3 exhibited a good correlation to MRI. Studies of clinical applications are warranted.

Magnetic Resonance Imaging for Axillary Breast Cancer Metastasis in the Neoadjuvant Setting: A Prospective Study.

BACKGROUND: Breast magnetic resonance imaging (MRI) for assessment of regional breast cancer metastasis is controversial owing to the variable specificity. We evaluated breast MRI for axillary metastasis in neoadjuvant chemotherapy patients. MATERIALS AND METHODS: A single-institution, institutional review board-approved prospective trial enrolled female breast cancer patients receiving neoadjuvant chemotherapy from 2008 to 2012 and collected the pre- and post-treatment MRI, pretreatment axillary ultrasound, axillary biopsy, and surgical pathologic findings. The kappa coefficient was used to evaluate the strength of the agreement between the 2 modalities and Fisher's exact test was used to evaluate the association. RESULTS: A total of 43 patients were included. Of these 45 patients, 35 had stage N1-N2 before treatment. Comparing the abnormal results on the pretreatment MRI scans and axillary biopsy examinations, a consistent diagnosis was found for 92%, with a moderate strength of agreement (kappa coefficient, 0.54). The pretreatment MRI findings were significantly associated with the axillary biopsy results (P = .014). The false-positive rate, false-negative rate, sensitivity, and specificity were 50%, 3%, 97%, 50%, respectively. Comparing the post-treatment MRI and surgical pathologic findings revealed a consistent diagnosis rate of, with a slight strength of agreement (kappa, 0.16). The false-positive rate, false-negative rate, sensitivity, and specificity were 38%, 46%, 55%, and 63%, respectively. The post-treatment MRI findings were not associated with the pathologic lymph node results (P = .342). CONCLUSION: Pretreatment breast MRI was more specific for axillary metastasis than was axillary ultrasonography. However, post-treatment breast MRI was not predictive of residual axillary disease and should be used cautiously when altering treatment plans.

Prospective trial of breast MRI versus 2D and 3D ultrasound for evaluation of response to neoadjuvant chemotherapy.

BACKGROUND: Preoperative imaging to assess response to neoadjuvant chemotherapy in breast cancer is routine but no single imaging modality is standard of practice. Our hypothesis is that ultrasound (US) is comparable to magnetic resonance imaging (MRI) in the prediction of residual disease. METHODS: A single-institution, Institutional Review Board-approved prospective trial of primary invasive ductal breast cancer patients receiving neoadjuvant chemotherapy enrolled women from 2008 to 2012. Two-dimensional (2D) and three-dimensional (3D) US, as well as MRI images of pre- and post-neoadjuvant tumors were obtained. Skin involvement or inadequate images were excluded. Residual tumor on imaging was compared with surgical pathology. Differences of tumor volume on imaging and pathology were compared using the non-parametric Wilcoxon signed-rank test. US to MRI agreement was determined by the kappa coefficient. Tumor volumes in estrogen receptor (ER), progesterone receptor (PR), and Her2neu subgroups were compared using the Kruskal-Wallis test. ER/PR staining <5 % was considered negative; Her2neu status was determined by in situ hybridization. RESULTS: Forty-two patients were enrolled in the study; 39 had evaluable post-treatment data. Four patients were Her2neu positive, and 17 (46 %) patients had triple-negative tumors. Among 11 (28 %) patients with pathologic complete response (pCR), US correctly predicted pCR in six (54.5 %) patients compared with eight (72.7 %) patients when MRI was used. This is a substantial agreement between US and MRI in predicting pCR (kappa = 0.62). There was no difference between 2D and 3D US modalities. For the 39 patients, US and MRI had no significant difference in volume estimation of pathology, even stratified by receptor status. CONCLUSION: The estimation of residual breast tumor volume by US and MRI achieves similar results, including prediction of pCR.

Magnetic resonance imaging-guided core needle breast biopsies resulting in high-risk histopathologic findings: upstage frequency and lesion characteristics.

UNLABELLED: Analysis of magnetic resonance imaging-guided breast biopsies yielding high-risk histopathologic features at a single institution found an overall upstage rate to malignancy of 14% at surgical excision. All upstaged lesions were associated with atypical ductal hyperplasia. Flat epithelial atypia and atypical lobular hyperplasia alone or with lobular carcinoma in situ were not associated with an upstage to malignancy. INTRODUCTION: The purpose of the present study w as to determine the malignancy upstage rates and imaging features of high-risk histopathologic findings resulting from magnetic resonance imaging (MRI)-guided core needle breast biopsies. These features include atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), flat epithelial atypia (FEA), and lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: A retrospective medical record review was performed on all MRI-guided core needle breast biopsies at a single institution from June 1, 2007 to December 1, 2013 to select biopsies yielding high-risk histopathologic findings. The patient demographics, MRI lesion characteristics, and histopathologic features at biopsy and surgical excision were analyzed. RESULTS: A total of 257 MRI-guided biopsies had been performed, and 50 yielded high-risk histopathologic features (19%). Biopsy site and surgical excision site correlation was confirmed in 29 of 50 cases. Four of 29 lesions (14%) were upstaged: 1 case to invasive ductal carcinoma and 3 cases to ductal carcinoma in situ. ADH alone had an overall upstage rate of 7% (1 of 14), mixed ADH/ALH a rate of 75% (3 of 4), ALH alone or with LCIS a rate of 0% (0 of 7), and FEA a rate of 0% (0 of 4). Only mixed ADH/ALH had a statistically significant upstage rate to malignancy compared with the other high-risk histopathologic subtypes combined. No specific imaging characteristics on MRI were associated with an upstage to malignancy on the statistical analysis. CONCLUSION: MRI-guided breast biopsies yielding high-risk histopathologic features were associated with an overall upstage to malignancy rate of 14% at surgical excision. All upstaged lesions were associated with ADH. FEA and ALH alone or with LCIS were not associated with an upstage to malignancy.

Short-term imaging follow-up of patients with concordant benign breast core needle biopsies: is it really worth it?

PURPOSE: Women with histologically proven concordant benign breast disease are often followed closely after biopsy for a period of two years, and they are considered to be at high-risk for cancer development. Our goal was to evaluate the utility of short-term (six-month) imaging follow-up and determine the incidence of breast cancer development in this population. METHODS: Retrospective review of concordant benign breast pathology was performed in 558 patients who underwent multimodality breast core biopsy. A total of 339 patients (60.7%) with 393 biopsies qualified for the study. The six-, 12-, and 24-month incidence rates of breast cancer development were estimated with 95% confidence intervals (CI), using the exact method binomial proportions. RESULTS: No cancer was detected in 285 of 339 patients (84.1%) returning for the six-month follow-up. No cancer was detected in 271 of 339 patients (79.9%) returning for the 12-month follow-up. Among 207 follow-up exams (61.1%) performed at 24 months, three patients were detected to have cancer in the ipsilateral breast (1.45% [95% CI, 0.30%-4.18%]) and two patients were detected to have cancer in the contralateral breast (0.97% [95% CI, 0.12%-3.45%]). Subsequent patient biopsy rate was 30 of 339 (8.85%, [95% CI, 6.05%-12.39%]). Three ipsilateral biopsies occurred as a sole result of the six-month follow-up of 285 patients (1.05%, [95% CI, 0.22%-3.05%]). CONCLUSION: Short-term imaging follow-up did not contribute to improved breast cancer detection, as all subsequent cancers were detected on annual mammography. Annual diagnostic mammography after benign breast biopsy may be sufficient.

Beyond mammography: new frontiers in breast cancer screening.

Breast cancer screening remains a subject of intense and, at times, passionate debate. Mammography has long been the mainstay of breast cancer detection and is the only screening test proven to reduce mortality. Although it remains the gold standard of breast cancer screening, there is increasing awareness of subpopulations of women for whom mammography has reduced sensitivity. Mammography also has undergone increased scrutiny for false positives and excessive biopsies, which increase radiation dose, cost, and patient anxiety. In response to these challenges, new technologies for breast cancer screening have been developed, including low-dose mammography, contrast-enhanced mammography, tomosynthesis, automated whole breast ultrasound, molecular imaging, and magnetic resonance imaging. Here we examine some of the current controversies and promising new technologies that may improve detection of breast cancer both in the general population and in high-risk groups, such as women with dense breasts. We propose that optimal breast cancer screening will ultimately require a personalized approach based on metrics of cancer risk with selective application of specific screening technologies best suited to the individual's age, risk, and breast density.

Differentiating fat necrosis from recurrent malignancy in fat-grafted breasts: an imaging classification system to guide management.

BACKGROUND: In breast reconstruction with autologous fat grafting, concerns persist about the ability to differentiate palpable masses representing fat necrosis from recurrent cancer. The authors' objective was to develop standardized imaging classifications to distinguish benign from malignant lesions after fat grafting. METHODS: A database of 286 breast reconstruction patients undergoing fat grafting from 2006 to 2011 was retrospectively reviewed to identify patients with imaging of clinically palpable masses. All images were reviewed independently by a radiologist blinded to prior results. Lesions were classified, using the American College of Radiology Breast Imaging Reporting and Data System ultrasound lexicon, as follows: A, solid mass, hypoechoic; B, solid mass, isoechoic; C, solid mass, hyperechoic; D, solid mass, complex echogenicity; E, anechoic mass with posterior acoustic enhancement; F, cystic mass with internal echoes; and G, negative. Evolutions in lesions on follow-up ultrasound were recorded. Images were correlated with histopathologic results. RESULTS: On ultrasound, 66 lesions were visualized in 37 patients with palpable masses. Twenty-two lesions (33 percent) were Breast Imaging Reporting and Data System category 4 lesions; biopsies were performed on all of them. Histopathologic results revealed that 85.7 percent (six of seven) with classification D and 100 percent with classifications A, B, C, E, F, and G were fat necrosis. The one malignant lesion (classification D) exhibited vascularity and angular margins on ultrasound and was not in the location of fat injection. Negative predictive value of avascularity and circumscribed margins for malignancy was 100 percent. Follow-up ultrasound of 29 lesions at a median of 6.5 months revealed that no masses increased in size or developed vascularity. CONCLUSION: Ultrasound analysis, with a standardized classification system, is reliable at differentiating benign from malignant lesions after fat grafting in breast reconstruction.

Clinical and imaging surveillance following breast cancer diagnosis.

Breast cancer is the most common malignancy affecting women worldwide. Women have a 1 in 8 lifetime risk of breast cancer. Breast conservation therapy (BCT) is the most common method of definitive treatment. Patients who previously have had to undergo mastectomy may be now eligible for BCT or a multitude of options for reconstruction, either immediate or delayed. Surveillance imaging after a breast cancer diagnosis is important because there is an increased risk of recurrence developing in patients, and early detection has been shown to improve survival. There is currently no consensus on a protocol for imaging the postoperative breast. In patients who have undergone mastectomy, detection of recurrence has mostly been via clinical symptoms and physical exam, often at a later stage. New imaging modalities, such as magnetic resonance imaging (MRI), ultrasound (US), and positron emission mammography (PEM) are changing the way we image the postsurgical breast. MRI, coupled with physical exam and mammography, approaches 100% sensitivity and high specificity for the identification of recurrent disease. We present a review of major academic institutions' imaging protocols and discuss the advantages of including MRI in traditional mammographic and clinical exams.