Susan P. Weinstein

How experience and training influence mammography expertise

RATIONALE AND OBJECTIVES The authors evaluated the influence of perceptual and cognitive skills in mammography detection and interpretation by testing three groups representing different levels of mammography expertise in terms of experience, training, and talent with a mammography screening-diagnostic task. MATERIALS AND METHODS One hundred fifty mammograms, composed of unilateral cranial-caudal and mediolateral oblique views, were displayed in pairs on a digital workstation to 19 radiology residents, three experienced mammographers, and nine mammography technologists. One-third of the mammograms showed malignant lesions; two-thirds were malignancy-free. Observers interacted with the display to indicate whether each image contained no malignant lesions or suspicious lesions indicating malignancy. Decision time was measured as the lesions were localized, classified, and rated for decision confidence. RESULTS Compared with performance of experts, alternative free response operating characteristic performance for residents was significantly lower and equivalent to that of technologists. Analysis of overall performance showed that, as level of expertise decreased, false-positive results exerted a greater effect on overall decision accuracy over the time course of image perception. This defines the decision speed-accuracy relationship that characterizes mammography expertise. CONCLUSION Differences in resident performance resulted primarily from lack of perceptual-learning experience during mammography training, which limited object recognition skills and made it difficult to determine differences between malignant lesions, benign lesions, and normal image perturbations. A proposed solution is systematic mentor-guided training that links image perception to feedback about the reasons underlying decision making.

A Review of Breast Ultrasound

Frequent advances in transducer design, electronics, computers, and signal processing have improved the quality of ultrasound images to the extent that sonography is now a major mode of imaging for the clinical diagnosis of breast cancer. Breast ultrasound is routinely used for differentiating cysts and solid nodules with high specificity. In combination with mammography, ultrasound is used to characterize solid masses as benign or malignant. There is growing interest in using Doppler ultrasound and contrast agents for measuring tumor blood flow and for imaging tumor vascularity. Ease of use and real-time imaging capability make breast ultrasound a method of choice for guiding breast biopsies and other interventional procedures. Breast ultrasound is used in many forms. B-mode is the most common form of imaging for the breast, although compound imaging and harmonic imaging are being increasingly applied to better visualize breast lesions and to reduce image artifacts. These developments, together with the formulation of a standardized lexicon of solid mass features, have improved the diagnostic performance of breast ultrasound. Several approaches that are currently being investigated to further improve performance include: (1) computer-aided-diagnosis; (2) the assessment of tumor vascularity and tumor blood flow with Doppler ultrasound and contrast agents; and (3) tissue elasticity imaging. In the future, ultrasound will play a greater role in differentiating benign from malignant masses and in the diagnosis of breast cancer.

HER-2/neu Overexpression as a Predictor for the Transition from In situ to Invasive Breast Cancer

The clinical implications of HER-2/neu (HER2) expression in ductal carcinoma in situ (DCIS) lesions have yet to be clearly elucidated; this despite the more frequent expression of HER2 in high-grade DCIS lesions compared with invasive cancers. We hypothesized that HER2 overexpression in DCIS is associated with more rapid progression to invasive disease. Immunohistochemical staining for estrogen receptor, progesterone receptor, and HER2 was done on DCIS specimens. Univariate analysis and a multivariate logistic regression were done to determine whether estrogen receptor, progesterone receptor, or HER2 status, comedo necrosis, nuclear grade, lesion size, or patient age predicted the presence of associated invasive disease in patients with DCIS. Invasive foci were found in association with HER2 overexpressing DCIS at a higher frequency than with DCIS that did not overexpress HER2. Although high nuclear grade, large lesion size, and HER2 overexpression were all associated with the presence of invasive disease on univariate analysis, HER2 was the only significant predictor for the presence of invasive disease after multivariate adjustment (odds ratio, 6.4; P = 0.01). These data indicate that HER2 overexpression in DCIS lesions predicts the presence of invasive foci in patients with DCIS and suggest that targeting of HER2 in an early disease setting may forestall or prevent disease progression. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1386–9)

HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ.

HER‐2/neu overexpression plays a critical role in breast cancer development, and its expression in ductal carcinoma in situ (DCIS) is associated with development of invasive breast cancer. A vaccine targeting HER‐2/neu expression in DCIS may initiate immunity against invasive cancer.

Multimodality Screening of High-Risk Women: A Prospective Cohort Study

PURPOSE Mammography has been established as the primary imaging screening method for breast cancer; however, the sensitivity of mammography is limited, especially in women with dense breast tissue. Given the limitations of mammography, interest has developed in alternative screening techniques. This interest has led to numerous studies reporting mammographically occult breast cancers detected on magnetic resonance imaging (MRI) or ultrasound. In addition, digital mammography was shown to be more sensitive than film mammography in selected populations. Our goal was to prospectively compare cancer detection of digital mammography (DM), whole-breast ultrasound (WBUS), and contrast-enhanced MRI in a high-risk screening population previously screened negative by film screen mammogram (FSM). METHODS During a 2-year period, 609 asymptomatic high-risk women with nonactionable FSM examinations presented for a prospective multimodality screening consisting of DM, WBUS, and MRI. The FSM examinations were reinterpreted by study radiologists. Patients had benign or no suspicious findings on clinical examination. The cancer yield by modality was evaluated. RESULTS Twenty cancers were diagnosed in 18 patients (nine ductal carcinomas in situ and 11 invasive breast cancers). The overall cancer yield on a per-patient basis was 3.0% (18 of 609 patients). The cancer yield by modality was 1.0% for FSM (six of 597 women), 1.2% for DM (seven of 569 women), 0.53% for WBUS (three of 567 women), and 2.1% for MRI (12 of 571 women). Of the 20 cancers detected, some were only detected on one imaging modality (FSM, n = 1; DM, n = 3; WBUS, n = 1; and MRI, n = 8). CONCLUSION The addition of MRI to mammography in the high-risk group has the greatest potential to detect additional mammographically occult cancers. The incremental cancer yield of WBUS and DM is much less.

FDG PET positive lymph nodes are highly predictive of metastasis in breast cancer

AimTo determine whether or not fluorodeoxyglucose positron emission tomography (FDG PET) imaging when positive could obviate the necessity for sentinel lymph node biopsy and for complete axillary node dissection in patients with breast cancer. MethodsA total of 80 female patients with a histological diagnosis of breast cancer and clinically negative axillary nodes underwent an FDG PET and sentinel lymph node biopsy (SLNB) or total axillary dissection for staging of axilla. Both SLNB and axillary dissection were performed in 72 patients, while eight patients had total axillary dissection without SLN biopsy. ResultsOf the 80 patients, 36 had lymph node metastasis on histopathology. SLNB was positive for metastasis in 35 (97%) of 36 patients (29 macrometastasis and seven micrometastasis). In the patient with false negative SLNB, the lymph node was completely replaced by the tumour. The FDG PET was true positive in 16 of 36 patients (sensitivity, 44%). There were two false positive studies with FDG PET, resulting in a specificity of 95%. The positive predictive value and accuracy of FDG PET for the detection of axillary lymph node metastasis were 89% and 72%, respectively. Univariate analysis revealed that higher grade of tumour, increased size and number of axillary lymph nodes were significantly associated with positive FDG PET results for axillary staging. ConclusionFDG PET cannot replace histological staging using SLNB in patients with breast cancer. However, FDG PET has a high specificity and positive predictive value for staging of the axilla in these patients. The patients with higher grade of tumour, larger size and higher number of axillary lymph nodes may be considered for FDG PET scan for axillary staging.

A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer

Twenty-seven patients with HER-2/neu overexpressing ductal carcinoma in situ of the breast were enrolled in a neoadjuvant immunization trial for safety and immunogenicity of DC1-polarized dendritic cells (DC1) pulsed with 6 HER-2/neu promiscuous major histocompatibility complex class II-binding peptides and 2 additional human leukocyte antigen (HLA)-A2.1 class I-binding peptides. DC1 were generated with interferon-&ggr; and a special clinical-grade bacterial endotoxin (lipopolysaccharide) and administered directly into groin lymph nodes 4 times at weekly intervals before scheduled surgical resection of ductal carcinoma in situ. Patients were monitored for the induction of new or enhanced antipeptide reactivity by interferon-&ggr; ELISPOT and enzyme-linked immunosorbentassays performed on Th cells obtained from peripheral blood or excised sentinel lymph nodes. Responses by cytotoxic T lymphocyte against HLA-A2.1-binding peptides were measured using peptide-pulsed T2 target cells or HER-2/neu-expressing or nonexpressing tumor cell lines. DC1 showed surface phenotype indistinct from “gold standard” inflammatory cocktail-activated DC, but displayed a number of distinguishing functional characteristics including the secretion of soluble factors and enhanced “killer DC” capacity against tumor cells in vitro. Postimmunization, we observed sensitization of Th cells to at least 1 class II peptide in 22 of 25 (88%; 95% exact confidence interval, 68.8%-97.5%) evaluable patients, whereas 11 of 13 (84.6%; 95% exact confidence interval, 64%-99.8%) HLA-A2.1 patients were successfully sensitized to class I peptides. Perhaps most importantly, anti-HER-2/neu peptide responses were observed up to 52-month postimmunization. These data show that even in the presence of early breast cancer such DC1 are potent inducers of durable type I-polarized immunity, suggesting potential clinical value for development of cancer immunotherapy.

Effectiveness of Digital Breast Tomosynthesis Compared With Digital Mammography: Outcomes Analysis From 3 Years of Breast Cancer Screening

IMPORTANCE Breast cancer screening with digital breast tomosynthesis (DBT) combined with digital mammography (DM) decreases false-positive examinations and increases cancer detection compared with screening with DM alone. However, the longitudinal performance of DBT screening is unknown. OBJECTIVES To determine whether the improved outcomes observed after initial implementation of DBT screening are sustainable over time at a population level and to evaluate the effect of more than 1 DBT screening at the individual level. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of screening mammography metrics was performed for all patients presenting for screening mammography in an urban, academic breast center during 4 consecutive years (DM, year 0; DBT, years, 1-3). The study was conducted from September 1, 2010, to September 30, 2014 (excluding September 2011, which was the transition period from DM to DBT), for a total of 44 468 screening events attributable to a total of 23 958 unique women. Differences in screening outcomes between each DBT year and the DM year, as well as between groups of women with only 1, 2, or 3 DBT screenings, were assessed, and the odds of recall adjusted for age, race/ethnicity, breast density, and prior mammograms were estimated. Data analysis was performed between February 16 and October 26, 2015. EXPOSURE Digital mammography screening supplemented with DBT. MAIN OUTCOMES AND MEASURES Recall rates, cancer cases per recalled patients, and biopsy and interval cancer rates were determined. RESULTS Screening outcome metrics were evaluated for a total of 44 468 examinations attributable to 23 958 unique women (mean [SD] age, 56.8 [11.0] years) over a 4-year period: year 0 cohort (DM0), 10 728 women; year 1 cohort (DBT1), 11 007; year 2 cohort (DBT2), 11 157; and year 3 cohort (DBT3), 11 576. Recall rates rose slightly for years 1 to 3 of DBT (88, 90, and 92 per 1000 screened, respectively) but remained significantly reduced compared with the DM0 rate of 104 per 1000 screened. Reported as odds ratios (95% CIs), the findings were DM vs DBT1, 0.83 (0.76-0.91, P < .001); DM vs DBT2, 0.85 (0.78-0.93, P < .001); and DM vs DBT3, 0.87 (0.80-0.95, P = .003). The cancer cases per recalled patients continued to rise from DM0 rate of 4.4% to 6.2% (P = .06), 6.5% (P = .03), and 6.7% (P = .02) for years 1 to 3 of DBT, respectively. Outcomes assessed for the most recent screening for individual women undergoing only 1, 2, or 3 DBT screenings during the study period demonstrated decreasing recall rates of 130, 78, and 59 per 1000 screened, respectively (P < .001). Interval cancer rates, determined using available follow-up data, decreased from 0.7 per 1000 women screened with the use of DM to 0.5 per 1000 screened with the use of DBT1. CONCLUSIONS AND RELEVANCE Digital breast tomosynthesis screening outcomes are sustainable, with significant recall reduction, increasing cancer cases per recalled patients, and a decline in interval cancers.

Frequency of Malignancy Seen in Probably Benign Lesions at Contrast-enhanced Breast MR Imaging: Findings from ACRIN 6667

PURPOSE To determine the frequency of malignancy in probably benign lesions seen at magnetic resonance (MR) screening of the contralateral breast in patients with known breast cancer enrolled in American College of Radiology Imaging Network (ACRIN) protocol 6667. MATERIALS AND METHODS ACRIN conducted a prospective multi-institutional MR imaging screening trial of the contralateral breast in women in whom breast cancer had been diagnosed recently. Each participating institution obtained institutional review board approval before patient accrual and was compliant with HIPAA. Informed consent was obtained from the patients. At enrollment, all women had negative clinical breast examination results and negative mammograms of the study breast. At image interpretation, radiologists scored lesions by using the Breast Imaging and Reporting and Data System (BI-RADS) lexicon. Of the 969 women who comprised the final study group, 106 were classified as having a BI-RADS category 3 lesion as their highest scoring lesion at MR imaging. There were 145 BI-RADS category 3 lesions in 106 patients. RESULTS In the 106 patients with at least one BI-RADS category 3 lesion, there were 37 masses (25.5%), 59 areas of nonmass enhancement (40.7%), and 47 foci of enhancement (32.4%). In two (1.4%) of these patients, no findings were reported. Eighty-three (78.3%) of the 106 patients had no evidence of malignancy in the study breast after 2 years of follow-up; the remaining 23 (21.7%) received a tissue diagnosis. Seventeen (16.0%) of the 106 patients elected to undergo biopsy. Biopsy was recommended in the remaining six patients (5.7%) on the basis of follow-up imaging findings. The biopsy results were benign in 18 (78%) of the 23 patients, whereas they showed atypical hyperplasia in two (9%). One (4%) of the 23 patients had ductal carcinoma in situ. Overall, malignancy was diagnosed in one (0.9%) of the 106 patients. CONCLUSION In a multi-institutional study, the frequency of malignancy in MR-detected BI-RADS category 3 lesions was 0.9% (95% confidence interval: 0.02%, 5.14%).

Automated chest wall line detection for whole-breast segmentation in sagittal breast MR images.

PURPOSE Breast magnetic resonance imaging (MRI) plays an important role in the clinical management of breast cancer. Computerized analysis is increasingly used to quantify breast MRI features in applications such as computer-aided lesion detection and fibroglandular tissue estimation for breast cancer risk assessment. Automated segmentation of the whole-breast as an organ from the other parts imaged is an important step in aiding lesion localization and fibroglandular tissue quantification. For this task, identifying the chest wall line (CWL) is most challenging due to image contrast variations, intensity discontinuity, and bias field. METHODS In this work, the authors develop and validate a fully automated image processing algorithm for accurate delineation of the CWL in sagittal breast MRI. The CWL detection is based on an integrated scheme of edge extraction and CWL candidate evaluation. The edge extraction consists of applying edge-enhancing filters and an edge linking algorithm. Increased accuracy is achieved by the synergistic use of multiple image inputs for edge extraction, where multiple CWL candidates are evaluated by the dynamic time warping algorithm coupled with the construction of a CWL reference. Their method is quantitatively validated by a dataset of 60 3D bilateral sagittal breast MRI scans (in total 3360 2D MR slices) that span the full American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density range. Agreement with manual segmentation obtained by an experienced breast imaging radiologist is assessed by both volumetric and boundary-based metrics, including four quantitative measures. RESULTS In terms of breast volume agreement with manual segmentation, the overlay percentage expressed by the Dices similarity coefficient is 95.0% and the difference percentage is 10.1%. More specifically, for the segmentation accuracy of the CWL boundary, the CWL overlay percentage is 92.7% and averaged deviation distance is 2.3 mm. Their method requires ≈ 4.5 min for segmenting each 3D breast MRI scan (56 slices) in comparison to ≈ 35 min required for manual segmentation. Further analysis indicates that the segmentation performance of their method is relatively stable across the different BI-RADS density categories and breast volume, and also robust with respect to a varying range of the major parameters of the algorithm. CONCLUSIONS Their fully automated method achieves high segmentation accuracy in a time-efficient manner. It could support large scale quantitative breast MRI analysis and holds the potential to become integrated into the clinical workflow for breast cancer clinical applications in the future.