Alexis V. Nees

Sentinel Lymph Node Biopsy Performed After Neoadjuvant Chemotherapy is Accurate in Patients with Documented Node-Positive Breast Cancer at Presentation

BackgroundThe optimal strategy for incorporating lymphatic mapping and sentinel lymph node biopsy into the management of breast cancer patients receiving neoadjuvant chemotherapy remains controversial. Previous studies of sentinel node biopsy performed following neoadjuvant chemotherapy have largely reported on patients whose prechemotherapy, pathologic axillary nodal status was unknown. We report findings using a novel comprehensive approach to axillary management of node-positive-patients receiving neoadjuvant chemotherapy.MethodsWe evaluated 54 consecutive breast cancer patients with biopsy-proven axillary nodal metastases at the time of diagnosis that underwent lymphatic mapping with nodal biopsy as well as concomitant axillary lymph node dissection after receiving neoadjuvant chemotherapy. All cases were treated at a single comprehensive cancer center between 2001 and 2005.ResultsThe sentinel node identification rate after delivery of neoadjuvant chemotherapy was 98%. Thirty-six patients (66%) had residual axillary metastases (including eight patients that had undergone resection of metastatic sentinel nodes at the time of diagnosis), and in 12 cases (31%) the residual metastatic disease was limited to the sentinel lymph node. The final, post-neoadjuvant chemotherapy sentinel node was falsely negative in three cases (8.6%). The negative final sentinel node accurately identified patients with no residual axillary disease in 17 cases (32%).ConclusionsSentinel lymph node biopsy performed after the delivery of neoadjuvant chemotherapy in patients with documented nodal disease at presentation accurately identified cases that may have been downstaged to node-negative status and can spare this subset of patients (32%) from experiencing the morbidity of an axillary dissection.

Comprehensive Axillary Evaluation in Neoadjuvant Chemotherapy Patients With Ultrasonography and Sentinel Lymph Node Biopsy

BackgroundThere is ongoing debate regarding the optimal sequence of sentinel lymph node (SLN) biopsy and neoadjuvant chemotherapy (CTX) for breast cancer. We report the accuracy of comprehensive pre–neoadjuvant CTX and post–neoadjuvant CTX axillary staging via ultrasound imaging, fine-needle aspiration (FNA) biopsy, and SLN biopsy.MethodsFrom 2001 to 2004, 91 neoadjuvant CTX patients at the University of Michigan Comprehensive Cancer Center underwent axillary staging by ultrasonography, ultrasound-guided FNA biopsy, SLN biopsy, or a combination of these.ResultsAxillary staging was pathologically negative by pre–neoadjuvant CTX SLN biopsy in 53 cases (58%); these patients had no further axillary surgery. In 38 cases (42%), axillary metastases were confirmed at presentation by either ultrasound-guided FNA or SLN biopsy. These 38 patients underwent completion axillary lymph node dissection (ALND) after delivery of neoadjuvant CTX. Follow-up lymphatic mapping was attempted in 33 of these cases, and the SLN was identified in 32 (identification rate, 97%). One third of these cases were completely node negative on ALND. Residual metastatic disease was identified in 22 cases, and the SLN was falsely negative in 1 (4.5%).ConclusionsPatients receiving neoadjuvant CTX can have accurate axillary nodal staging by ultrasound-guided FNA or SLN biopsy. In cases of documented axillary metastasis at presentation, repeat axillary staging with SLN biopsy can document the post–neoadjuvant CTX nodal status. This strategy optimizes pre–neoadjuvant CTX and post–neoadjuvant CTX staging information by distinguishing the patients who are node negative at presentation from those who have been downstaged to node negativity and offers the potential for avoiding unnecessary ALNDs in both of these patient subsets.

Computerized characterization of breast masses on three-dimensional ultrasound volumes.

We are developing computer vision techniques for the characterization of breast masses as malignant or benign on radiologic examinations. In this study, we investigated the computerized characterization of breast masses on three-dimensional (3-D) ultrasound (US) volumetric images. We developed 2-D and 3-D active contour models for automated segmentation of the mass volumes. The effect of the initialization method of the active contour on the robustness of the iterative segmentation method was studied by varying the contour used for its initialization. For a given segmentation, texture and morphological features were automatically extracted from the segmented masses and their margins. Stepwise discriminant analysis with the leave-one-out method was used to select effective features for the classification task and to combine these features into a malignancy score. The classification accuracy was evaluated using the area Az under the receiver operating characteristic (ROC) curve, as well as the partial area index Az(0.9), defined as the relative area under the ROC curve above a sensitivity threshold of 0.9. For the purpose of comparison with the computer classifier, four experienced breast radiologists provided malignancy ratings for the 3-D US masses. Our dataset consisted of 3-D US volumes of 102 biopsied masses (46 benign, 56 malignant). The classifiers based on 2-D and 3-D segmentation methods achieved test Az values of 0.87+/-0.03 and 0.92+/-0.03, respectively. The difference in the Az values of the two computer classifiers did not achieve statistical significance. The Az values of the four radiologists ranged between 0.84 and 0.92. The difference between the computers Az value and that of any of the four radiologists did not achieve statistical significance either. However, the computers Az(0.9) value was significantly higher than that of three of the four radiologists. Our results indicate that an automated and effective computer classifier can be designed for differentiating malignant and benign breast masses on 3-D US volumes. The accuracy of the classifier designed in this study was similar to that of experienced breast radiologists.

ROC study of the effect of stereoscopic imaging on assessment of breast lesions

An observer performance study was conducted to evaluate the usefulness of assessing breast lesion characteristics with stereomammography. Stereoscopic image pairs of 158 breast biopsy tissue specimens were acquired with a GE Senographe 2000D full field digital mammography system using a 1.8x magnification geometry. A phantom-shift method equivalent to a stereo shift angle of +/- 3 degrees relative to a central axis perpendicular to the detector was used. For each specimen, two pairs of stereo images were taken at approximately orthogonal orientations. The specimens contained either a mass, microcalcifications, both, or normal tissue. Based on pathological analysis, 39.9% of the specimens were found to contain malignancy. The digital specimen radiographs were displayed on a high resolution MegaScan CRT monitor driven by a DOME stereo display board using in-house developed software. Five MQSA radiologists participated as observers. Each observer read the 316 specimen stereo image pairs in a randomized order. For each case, the observer first read the monoscopic image and entered his/her confidence ratings on the presence of microcalcifications and/or masses, margin status, BI-RADS assessment, and the likelihood of malignancy. The corresponding stereoscopic images were then displayed on the same monitor and were viewed through stereoscopic LCD glasses. The observer was free to change the ratings in every category after stereoscopic reading. The ratings of the observers were analyzed by ROC methodology. For the 5 MQSA radiologists, the average Az value for estimation of the likelihood of malignancy of the lesions improved from 0.70 for monoscopic reading to 0.72 (p=0.04) after stereoscopic reading, and the average Az value for the presence of microcalcifications improved from 0.95 to 0.96 (p=0.02). The Az value for the presence of masses improved from 0.80 to 0.82 after stereoscopic reading, but the difference fell short of statistical significance (p=0.08). The visual assessment of margin clearance was found to have very low correlation with microscopic analysis with or without stereoscopic reading. This study demonstrates the potential of using stereomammography to improve the detection and characterization of mammographic lesions.

Outcome of Men Presenting with Clinical Breast Problems: The Role of Mammography and Ultrasound

Abstract:  The purpose of this study was to determine the outcome of men presenting with clinical breast problems for breast imaging and to evaluate the role of mammography and ultrasound in the diagnosis of benign and malignant breast problems. We retrospectively reviewed clinical, radiographic, and pathologic records of 165 consecutive symptomatic men presenting to Breast Imaging over a 4 year period. We assessed the clinical indication for referral, mammographic findings, sonographic findings, histologic results, and clinical outcomes. Patients ranged in age from 22 to 96 years. Breast Imaging Reporting and Data System (BI‐RADS) category 4 and 5 mammograms and solid sonographic masses were considered suspicious for malignancy. Six of 165 men (4%) had primary breast carcinoma, which were mammographically suspicious in all 6 (100%). Five were invasive ductal carcinoma and one was ductal carcinoma in situ (DCIS). Of 164 mammograms, 20 (12%) were suspicious. Six were cancer and 14 were benign. Clinical follow‐up for 2 years or biopsy results were available for 138 of the 165 men (84%). Twelve with benign mammographic findings had benign biopsies. All men with benign mammography not undergoing biopsy were cancer free. Sensitivity for cancer detection (mammography) was 100% and specificity was 90%. Positive predictive value (mammography) was 32% (6 of 19) and the negative predictive value was 100%. Sonography was performed in 68 of the 165 men (41%). Three of three cancers (100%) were solid sonographic masses. There were 9 of 68 false‐positive examinations (13%). Sensitivity and negative predictive value for cancer detection (ultrasound) was 100% and specificity was 74%. The most common clinical indication for referral was mass/thickening (56%). Mammography had excellent sensitivity and specificity for breast cancer detection and should be included as the initial imaging examination of men with clinical breast problems. The negative predictive value of 100% for mammography suggests that mammograms read as normal or negative need no further examination if the clinical findings are not suspicious. A normal ultrasound in these men confirms the negative predictive value of a normal mammogram.

Multi-modality 3D breast imaging with X-Ray tomosynthesis and automated ultrasound

This study evaluated the utility of 3D automated ultrasound in conjunction with 3D digital X-ray tomosynthesis for breast cancer detection and assessment, to better localize and characterize lesions in the breast. Tomosynthesis image volumes and automated ultrasound image volumes were acquired in the same geometry and in the same view for 27 patients. 3 MQSA certified radiologists independently reviewed the image volumes, visually correlating the images from the two modalities with in-house software. More sophisticated software was used on a smaller set of 10 cases, which enabled the radiologist to draw a 3D box around the suspicious lesion in one image set and isolate an anatomically correlated, similarly boxed region in the other modality image set. In the primary study, correlation was found to be moderately useful to the readers. In the additional study, using improved software, the median usefulness rating increased and confidence in localizing and identifying the suspicious mass increased in more than half the cases. As automated scanning and reading software techniques advance, superior results are expected.

Digital Breast Tomosynthesis: Observer Performance of Clustered Microcalcification Detection on Breast Phantom Images Acquired with an Experimental System Using Variable Scan Angles, Angular Increments, and Number of Projection Views

PURPOSE To investigate the dependence of microcalcification cluster detectability on tomographic scan angle, angular increment, and number of projection views acquired at digital breast tomosynthesis ( DBT digital breast tomosynthesis ). MATERIALS AND METHODS A prototype DBT digital breast tomosynthesis system operated in step-and-shoot mode was used to image breast phantoms. Four 5-cm-thick phantoms embedded with 81 simulated microcalcification clusters of three speck sizes (subtle, medium, and obvious) were imaged by using a rhodium target and rhodium filter with 29 kV, 50 mAs, and seven acquisition protocols. Fixed angular increments were used in four protocols (denoted as scan angle, angular increment, and number of projection views, respectively: 16°, 1°, and 17; 24°, 3°, and nine; 30°, 3°, and 11; and 60°, 3°, and 21), and variable increments were used in three (40°, variable, and 13; 40°, variable, and 15; and 60°, variable, and 21). The reconstructed DBT digital breast tomosynthesis images were interpreted by six radiologists who located the microcalcification clusters and rated their conspicuity. RESULTS The mean sensitivity for detection of subtle clusters ranged from 80% (22.5 of 28) to 96% (26.8 of 28) for the seven DBT digital breast tomosynthesis protocols; the highest sensitivity was achieved with the 16°, 1°, and 17 protocol (96%), but the difference was significant only for the 60°, 3°, and 21 protocol (80%, P < .002) and did not reach significance for the other five protocols (P = .01-.15). The mean sensitivity for detection of medium and obvious clusters ranged from 97% (28.2 of 29) to 100% (24 of 24), but the differences fell short of significance (P = .08 to >.99). The conspicuity of subtle and medium clusters with the 16°, 1°, and 17 protocol was rated higher than those with other protocols; the differences were significant for subtle clusters with the 24°, 3°, and nine protocol and for medium clusters with 24°, 3°, and nine; 30°, 3°, and 11; 60°, 3° and 21; and 60°, variable, and 21 protocols (P < .002). CONCLUSION With imaging that did not include x-ray source motion or patient motion during acquisition of the projection views, narrow-angle DBT digital breast tomosynthesis provided higher sensitivity and conspicuity than wide-angle DBT digital breast tomosynthesis for subtle microcalcification clusters.

Digital Mammography: Are There Advantages in Screening for Breast Cancer?

Digital mammography separates the processes of image acquisition, processing, and display, which allows for the optimization of each process. The result addresses some of the limitations of screen film mammography. This work reviews the advantages of the decoupling of the processes and the clinical trials comparing digital mammography with film-screen mammography in the screening setting. Advanced applications of digital mammography, such as contrast-enhanced digital mammography and tomosynthesis, are also discussed.

A similarity study of content-based image retrieval system for breast cancer using decision tree.

PURPOSE We are developing a decision tree content-based image retrieval (DTCBIR) CADx system to assist radiologists in characterization of breast masses on ultrasound images. METHODS Three DTCBIR configurations, including decision tree with boosting (DTb), decision tree with full leaf features (DTL), and decision tree with selected leaf features (DTLs) were compared. For DTb, features of a query mass were combined first into a merged feature score and then masses with similar scores were retrieved. For DTL and DTLs, similar masses were retrieved based on the Euclidean distance between feature vectors of the query and those of selected references. For each DTCBIR configuration, we investigated the use of full feature set and subset of features selected by the stepwise linear discriminant analysis (LDA) and simplex optimization method, resulting in six retrieval methods and selected five, DTb-lda, DTL-lda, DTb-full, DTL-full, and DTLs-full, for the observer study. Three MQSA radiologists rated similarities between the query mass and computer-retrieved three most similar masses using nine-point similarity scale (9 = very similar). RESULTS For DTb-lda, DTL-lda, DTb-full, DTL-full, and DTLs-full, average A(z) values were 0.90 ± 0.03, 0.85 ± 0.04, 0.87 ± 0.04, 0.79 ± 0.05, and 0.71 ± 0.06, respectively, and average similarity ratings were 5.00, 5.41, 4.96, 5.33, and 5.13, respectively. CONCLUSIONS The DTL-lda is a promising DTCBIR CADx configuration which had simple tree structure, good classification performance, and highest similarity rating.

ROC study: effects of computer-aided diagnosis on radiologists' characterization of malignant and benign breast masses in temporal pairs of mammograms

We conducted an observer performance study using receiver operating characteristic (ROC) methodology to evaluate the effects of computer-aided diagnosis (CAD) on radiologists’ performance for characterization of masses on serial mammograms. The automated CAD system, previously developed in our laboratory, can classify masses as malignant or benign based on interval change information on serial mammograms. In this study, 126 temporal image pairs (73 malignant and 53 benign) from 52 patients containing masses on serial mammograms were used. The corresponding masses on each temporal pair were identified by an experienced radiologist and automatically segmented by the CAD program. Morphological, texture, and spiculation features of the mass on the current and the prior mammograms were extracted. The individual features and the difference between the corresponding current and prior features formed a multidimensional feature space. A subset of the most effective features that contained the current, prior, and interval change information was selected by a stepwise procedure and used as input predictor variables to a linear discriminant classifier in a leave-one-case-out training and testing resampling scheme. The linear discriminant classifier estimated the relative likelihood of malignancy of each mass. The classifier achieved a test Az value of 0.87. For the ROC study, 4 MQSA radiologists and 1 breast imaging fellow assessed the masses on the temporal pairs and provided estimates of the likelihood of malignancy without and with CAD. The average Az value for the likelihood of malignancy estimated by the radiologists was 0.79 without CAD and improved to 0.87 with CAD. The improvement was statistically significant (p=0.0003). This preliminary result indicated that CAD using interval change analysis can significantly improve radiologists’ accuracy in classification of masses and thereby may increase the positive predictive value of mammography.