David Schacht

Importance of a Personal History of Breast Cancer as a Risk Factor for the Development of Subsequent Breast Cancer: Results From Screening Breast MRI

OBJECTIVE The purposes of this study were to assess the importance of a personal history of breast cancer as a risk factor for patients referred for screening breast MRI and to evaluate the importance of this risk factor compared with family history. MATERIALS AND METHODS A retrospective review of screening breast MRI performed from 2004 to 2012 included a total of 702 patients, 465 of whom had undergone annual MRI and 237 of whom had undergone MRI every 6 months as part of a research protocol. RESULTS Of the patients screened, 208 had a personal history of breast cancer, and 345 had a family history as the sole risk factor. An additional 97 patients had both risk factors. The absolute risk for detection of breast cancer at screening MRI among patients with a personal history of cancer was 2.8% (95% CI, 0.6-5.2%). The absolute risk for patients with a strong family history of cancer was 2.0% (95% CI, 0.5-3.5%). The relative risk for detection of breast cancer given a personal history was 1.42 (95% CI, 0.48-4.17) compared with family history. The relative risk when both risk factors were present compared with having only a family history was 3.04 (95% CI, 1.05-8.86). CONCLUSION A personal history of breast cancer is an important risk factor for the development of subsequent breast cancer. Given the results, consideration should be given to MRI screening of patients with a personal history of breast cancer.

Utility of Preoperative Ultrasound for Predicting pN2 or Higher Stage Axillary Lymph Node Involvement in Patients With Newly Diagnosed Breast Cancer

OBJECTIVE The objective of our study was to report the positive predictive value (PPV) of ultrasound of the axilla to predict pN2 or higher disease in breast cancer patients. MATERIALS AND METHODS A retrospective study of 559 patients with newly diagnosed invasive breast cancer from 2005 through 2009 was performed. All patients underwent ipsilateral axillary ultrasound for staging purposes. Ultrasound findings were considered suspicious for metastasis if cortical thickening or nonhilar blood flow to the cortex was present. Suspicious lymph nodes were classified on the basis of their features as high, intermediate, or low suspicion. The standard of truth was confirmed pathologically. RESULTS Either pN2 or pN3 disease was found in 50 of 181 (28%) patients with positive findings on an ultrasound study and 10 of 378 (3%) patients with a negative ultrasound study (p < 0.01). When two or more lymph nodes of high suspicion or a total of three or more lymph nodes of any combination of high suspicion and intermediate suspicion were detected, patients were likely to have pN2 or pN3 disease (PPV, 82%). Either pN2 or pN3 disease was found in two of 122 (2%) patients whose primary cancers were up to 10 mm and 58 of 437 (13%) patients whose primary cancers were larger than 10 mm (p < 0.001). Ultrasound of the patient with tumors larger than 10 mm showing at least two highly suspicious nodes had a PPV of 87% for predicting pN2 or higher disease. CONCLUSION Ultrasound was useful for predicting pN2 or higher axillary disease in breast cancer patients. Preoperative ultrasound assessment for staging of axillary lymph nodes might help avoid underestimation at sentinel lymph node biopsy.

Accuracy of axillary lymph node staging in breast cancer patients: an observer-performance study comparison of MRI and ultrasound.

PURPOSE To compare magnetic resonance imaging (MRI) and ultrasound (US) for axillary lymph node (LN) staging in breast cancer patients in an observer-performance study. MATERIALS AND METHODS An observer-performance study was conducted with five breast radiologists reviewing 50 consecutive patients of newly diagnosed invasive breast cancer with the use of ipsilateral axillary MRI and US. LN status was pathologically proved in all patients. Each observer reviewed the images in two separate sessions: one for MRI and the other for US. Observers were asked to indicate their confidence of the presence of at least one ipsilateral metastatic LN on a quasi-continuous rating scale and whether they recommend percutaneous biopsy preoperatively. Receiver operating characteristic (ROC) analysis and area under the ROC curve were used to characterize diagnostic performance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated from whether observers recommended biopsy. RESULTS There were no statistically significant differences in each observers performance between MRI and US, or in the performance of all observers as a group, in terms of ROC analysis. There were no statistically significant differences in sensitivity, specificity, PPV, or NPV between MRI and US, but there were statistically significant improvements in specificity and PPV from either MRI or US alone to MRI and US combined. CONCLUSIONS Observer performance on MRI and US are comparable for axillary LN staging. When US and MRI are concordant for positive findings, higher specificity and PPV can be obtained.

Effect of mutation of two critical glutamic acid residues on the activity and stability of human carboxypeptidase M and characterization of its signal for glycosylphosphatidylinositol anchoring

Human carboxypeptidase (CP) M was expressed in baculovirus-infected insect cells in a glycosylphosphatidylinositol-anchored form, whereas a truncated form, lacking the putative signal sequence for glycosylphosphatidylinositol anchoring, was secreted at high levels into the medium. Both forms had lower molecular masses (50 kDa) than native placental CPM (62 kDa), indicating minimal glycosylation. The predicted glycosylphosphatidylinositol-anchor attachment site was investigated by mutation of Ser(406) to Ala, Thr or Pro and expression in HEK-293 and COS-7 cells. The wild-type and S406A and S406T mutants were expressed on the plasma membrane in glycosylphosphatidylinositol-anchored form, but the S406P mutant was not and was retained in a perinuclear location. The roles of Glu(260) and Glu(264) in CPM were investigated by site-directed mutagenesis. Mutation of Glu(260) to Gln had minimal effects on kinetic parameters, but decreased heat stability, whereas mutation to Ala reduced the k(cat)/ K(m) by 104-fold and further decreased stability. In contrast, mutation of Glu(264) to Gln resulted in a 10000-fold decrease in activity, but the enzyme still bound to p-aminobenzoylarginine-Sepharose and was resistant to trypsin treatment, indicating that the protein was folded properly. These results show that Glu(264) is the critical catalytic glutamic acid and that Glu(260) probably stabilizes the conformation of the active site.

Kinetic Analysis of Benign and Malignant Breast Lesions With Ultrafast Dynamic Contrast-Enhanced MRI: Comparison With Standard Kinetic Assessment

OBJECTIVE The purposes of this study were to evaluate diagnostic parameters measured with ultrafast MRI acquisition and with standard acquisition and to compare diagnostic utility for differentiating benign from malignant lesions. MATERIALS AND METHODS Ultrafast acquisition is a high-temporal-resolution (7 seconds) imaging technique for obtaining 3D whole-breast images. The dynamic contrast-enhanced 3-T MRI protocol consists of an unenhanced standard and an ultrafast acquisition that includes eight contrast-enhanced ultrafast images and four standard images. Retrospective assessment was performed for 60 patients with 33 malignant and 29 benign lesions. A computer-aided detection system was used to obtain initial enhancement rate and signal enhancement ratio (SER) by means of identification of a voxel showing the highest signal intensity in the first phase of standard imaging. From the same voxel, the enhancement rate at each time point of the ultrafast acquisition and the AUC of the kinetic curve from zero to each time point of ultrafast imaging were obtained. RESULTS There was a statistically significant difference between benign and malignant lesions in enhancement rate and kinetic AUC for ultrafast imaging and also in initial enhancement rate and SER for standard imaging. ROC analysis showed no significant differences between enhancement rate in ultrafast imaging and SER or initial enhancement rate in standard imaging. CONCLUSION Ultrafast imaging is useful for discriminating benign from malignant lesions. The differential utility of ultrafast imaging is comparable to that of standard kinetic assessment in a shorter study time.

Decision Making for Breast Lesions Initially Detected at Contrast-Enhanced Breast MRI

OBJECTIVE The purpose of this study was to assess the clinical significance of breast lesions initially detected at contrast-enhanced breast MRI and to consider how to manage those lesions in accordance with the imaging findings and the indication for MRI. MATERIALS AND METHODS A retrospective study of 4260 consecutive breast MRI examinations was performed to identify MRI-detected enhancing lesions. In 4260 studies, 554 MRI-detected lesions were found in 417 patients, and 134 (24%) of the lesions were malignant. Pathologic confirmation was obtained for 319 (58%) lesions. Results of the subsequent imaging workup, biopsy, surgery, and imaging follow-up were reviewed. RESULTS The median size of the lesions was 89 mm (malignant, 15.45 mm; benign, 7.48 mm). Irregular shape, irregular or spiculated margins, and heterogeneous or rim enhancement were seen significantly more often in malignant mass lesions (p < 0.001). Malignant lesions were more likely to exhibit rapid enhancement (p < 0.001). Benign lesions were more likely to have persistent kinetics (p < 0.001). There was a statistically significant difference (p < 0.001) between malignant (58/87, 67%) and benign lesions (128/287, 45%) with respect to sonographic detection at second-look ultrasound examinations. Malignant lesions were most often detected in patients with metastatic axillary lymph nodes with an unknown primary tumor (8/8, 100%), followed by patients with positive or close margins in recent breast cancer surgery (45/76, 59%), and patients with newly diagnosed breast cancer (44/115, 38%). CONCLUSION Management of MRI-detected lesions should be based on both MRI findings and the patients indication for MRI.

Breast Cancer Detected on an Incident (Second or Subsequent) Round of Screening MRI: MRI Features of False-Negative Cases

OBJECTIVE The purpose of this article is to evaluate the nature of breast cancers detected in the incident round of screening MRI to determine MRI features of early breast cancer. MATERIALS AND METHODS From 2003 to 2012, there were 16 incident breast cancers in 15 patients on screening MRI, including nine cancers that were retrospectively identifiable on the prior MRI (false-negative [FN] cancers at prior screening examination). We evaluated the BI-RADS features of these incident cancers in previous and current MRI scans. RESULTS Of 16 incident cancers, there were 11 mass lesions (69%), three foci (19%), and two nonmasslike enhancement lesions (13%). Of the nine FN cancers (five foci, two masses, and two nonmasslike enhancement lesions), all showed increases in size on the current examination (median, 80% increase); four lesions showed rapid uptake kinetics on prior examinations, and five lesions showed a change in kinetic pattern from slow to rapid uptake. Among the five foci, one focus was isolated and four foci were in a background of other foci, where two foci could be distinguished for their higher signal intensity. CONCLUSION On screening MRI, any lesion that increases in size, has rapid uptake kinetics or a change in kinetic pattern, or is an isolated focus or focus showing more enhancement than other foci should be viewed with a high degree of suspicion, and a biopsy should be considered.

Diffusion weighted images of metastatic as compared with nonmetastatic axillary lymph nodes in patients with newly diagnosed breast cancer

To investigate the ability of diffusion weighted images (DWI) to differentiate between metastatic and nonmetastatic axillary lymph nodes (LNs) in patients with newly diagnosed breast cancer.

Using quantitative image analysis to classify axillary lymph nodes on breast MRI: A new application for the Z 0011 Era

PURPOSE To assess the performance of computer extracted feature analysis of dynamic contrast enhanced (DCE) magnetic resonance images (MRI) of axillary lymph nodes. To determine which quantitative features best predict nodal metastasis. METHODS This institutional board-approved HIPAA compliant study, in which informed patient consent was waived, collected enhanced T1 images of the axilla from patients with breast cancer. Lesion segmentation and feature analysis were performed on 192 nodes using a laboratory-developed quantitative image analysis (QIA) workstation. The importance of 28 features were assessed. Classification used the features as input to a neural net classifier in a leave-one-case-out cross-validation and evaluated with receiver operating characteristic (ROC) analysis. RESULTS The area under the ROC curve (AUC) values for features in the task of distinguishing between positive and negative nodes ranged from just over 0.50 to 0.70. Five features yielded AUCs greater than 0.65: two morphological and three textural features. In cross-validation, the neural net classifier obtained an AUC of 0.88 (SE 0.03) for the task of distinguishing between positive and negative nodes. CONCLUSION QIA of DCE MRI demonstrated promising performance in discriminating between positive and negative axillary nodes.

Evaluation of Kinetic Entropy of Breast Masses Initially Found on MRI using Whole-lesion Curve Distribution Data: Comparison with the Standard Kinetic Analysis

ObjectivesTo quantify kinetic heterogeneity of breast masses that were initially detected with dynamic contrast-enhanced MRI, using whole-lesion kinetic distribution data obtained from computer-aided evaluation (CAE), and to compare that with standard kinetic curve analysis.MethodsClinical MR images from 2006 to 2011 with breast masses initially detected with MRI were evaluated with CAE. The relative frequencies of six kinetic patterns (medium-persistent, medium-plateau, medium-washout, rapid-persistent, rapid-plateau, rapid-washout) within the entire lesion were used to calculate kinetic entropy (KE), a quantitative measure of enhancement pattern heterogeneity. Initial uptake (IU) and signal enhancement ratio (SER) were obtained from the most-suspicious kinetic curve. Mann-Whitney U test and ROC analysis were conducted for differentiation of malignant and benign masses.ResultsForty benign and 37 malignant masses comprised the case set. IU and SER were not significantly different between malignant and benign masses, whereas KE was significantly greater for malignant than benign masses (p = 0.748, p = 0.083, and p < 0.0001, respectively). Areas under ROC curve for IU, SER, and KE were 0.479, 0.615, and 0.662, respectively.ConclusionQuantification of kinetic heterogeneity of whole-lesion time-curve data with KE has the potential to improve differentiation of malignant from benign breast masses on breast MRI.Key points• Kinetic heterogeneity can be quantified by computer-aided evaluation of breast MRI• Kinetic entropy was greater in malignant masses than benign masses• Kinetic entropy has the potential to improve differentiation of breast masses