Ellen B. Mendelson

Combined Screening With Ultrasound and Mammography vs Mammography Alone in Women at Elevated Risk of Breast Cancer

CONTEXT Screening ultrasound may depict small, node-negative breast cancers not seen on mammography. OBJECTIVE To compare the diagnostic yield, defined as the proportion of women with positive screen test results and positive reference standard, and performance of screening with ultrasound plus mammography vs mammography alone in women at elevated risk of breast cancer. DESIGN, SETTING, AND PARTICIPANTS From April 2004 to February 2006, 2809 women, with at least heterogeneously dense breast tissue in at least 1 quadrant, were recruited from 21 sites to undergo mammographic and physician-performed ultrasonographic examinations in randomized order by a radiologist masked to the other examination results. Reference standard was defined as a combination of pathology and 12-month follow-up and was available for 2637 (96.8%) of the 2725 eligible participants. MAIN OUTCOME MEASURES Diagnostic yield, sensitivity, specificity, and diagnostic accuracy (assessed by the area under the receiver operating characteristic curve) of combined mammography plus ultrasound vs mammography alone and the positive predictive value of biopsy recommendations for mammography plus ultrasound vs mammography alone. RESULTS Forty participants (41 breasts) were diagnosed with cancer: 8 suspicious on both ultrasound and mammography, 12 on ultrasound alone, 12 on mammography alone, and 8 participants (9 breasts) on neither. The diagnostic yield for mammography was 7.6 per 1000 women screened (20 of 2637) and increased to 11.8 per 1000 (31 of 2637) for combined mammography plus ultrasound; the supplemental yield was 4.2 per 1000 women screened (95% confidence interval [CI], 1.1-7.2 per 1000; P = .003 that supplemental yield is 0). The diagnostic accuracy for mammography was 0.78 (95% CI, 0.67-0.87) and increased to 0.91 (95% CI, 0.84-0.96) for mammography plus ultrasound (P = .003 that difference is 0). Of 12 supplemental cancers detected by ultrasound alone, 11 (92%) were invasive with a median size of 10 mm (range, 5-40 mm; mean [SE], 12.6 [3.0] mm) and 8 of the 9 lesions (89%) reported had negative nodes. The positive predictive value of biopsy recommendation after full diagnostic workup was 19 of 84 for mammography (22.6%; 95% CI, 14.2%-33%), 21 of 235 for ultrasound (8.9%, 95% CI, 5.6%-13.3%), and 31 of 276 for combined mammography plus ultrasound (11.2%; 95% CI. 7.8%-15.6%). CONCLUSIONS Adding a single screening ultrasound to mammography will yield an additional 1.1 to 7.2 cancers per 1000 high-risk women, but it will also substantially increase the number of false positives. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00072501.

Detection of Breast Cancer with Addition of Annual Screening Ultrasound or a Single Screening MRI to Mammography in Women with Elevated Breast Cancer Risk

CONTEXT Annual ultrasound screening may detect small, node-negative breast cancers that are not seen on mammography. Magnetic resonance imaging (MRI) may reveal additional breast cancers missed by both mammography and ultrasound screening. OBJECTIVE To determine supplemental cancer detection yield of ultrasound and MRI in women at elevated risk for breast cancer. DESIGN, SETTING, AND PARTICIPANTS From April 2004-February 2006, 2809 women at 21 sites with elevated cancer risk and dense breasts consented to 3 annual independent screens with mammography and ultrasound in randomized order. After 3 rounds of both screenings, 612 of 703 women who chose to undergo an MRI had complete data. The reference standard was defined as a combination of pathology (biopsy results that showed in situ or infiltrating ductal carcinoma or infiltrating lobular carcinoma in the breast or axillary lymph nodes) and 12-month follow-up. MAIN OUTCOME MEASURES Cancer detection rate (yield), sensitivity, specificity, positive predictive value (PPV3) of biopsies performed and interval cancer rate. RESULTS A total of 2662 women underwent 7473 mammogram and ultrasound screenings, 110 of whom had 111 breast cancer events: 33 detected by mammography only, 32 by ultrasound only, 26 by both, and 9 by MRI after mammography plus ultrasound; 11 were not detected by any imaging screen. Among 4814 incidence screens in the second and third years combined, 75 women were diagnosed with cancer. Supplemental incidence-screening ultrasound identified 3.7 cancers per 1000 screens (95% CI, 2.1-5.8; P < .001). Sensitivity for mammography plus ultrasound was 0.76 (95% CI, 0.65-0.85); specificity, 0.84 (95% CI, 0.83-0.85); and PPV3, 0.16 (95% CI, 0.12-0.21). For mammography alone, sensitivity was 0.52 (95% CI, 0.40-0.64); specificity, 0.91 (95% CI, 0.90-0.92); and PPV3, 0.38 (95% CI, 0.28-0.49; P < .001 all comparisons). Of the MRI participants, 16 women (2.6%) had breast cancer diagnosed. The supplemental yield of MRI was 14.7 per 1000 (95% CI, 3.5-25.9; P = .004). Sensitivity for MRI and mammography plus ultrasound was 1.00 (95% CI, 0.79-1.00); specificity, 0.65 (95% CI, 0.61-0.69); and PPV3, 0.19 (95% CI, 0.11-0.29). For mammography and ultrasound, sensitivity was 0.44 (95% CI, 0.20-0.70, P = .004); specificity 0.84 (95% CI, 0.81-0.87; P < .001); and PPV3, 0.18 (95% CI, 0.08 to 0.34; P = .98). The number of screens needed to detect 1 cancer was 127 (95% CI, 99-167) for mammography; 234 (95% CI, 173-345) for supplemental ultrasound; and 68 (95% CI, 39-286) for MRI after negative mammography and ultrasound results. CONCLUSION The addition of screening ultrasound or MRI to mammography in women at increased risk of breast cancer resulted in not only a higher cancer detection yield but also an increase in false-positive findings. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00072501.

Breast Cancer Screening With Imaging: Recommendations From the Society of Breast Imaging and the ACR on the Use of Mammography, Breast MRI, Breast Ultrasound, and Other Technologies for the Detection of Clinically Occult Breast Cancer

Screening for breast cancer with mammography has been shown to decrease mortality from breast cancer, and mammography is the mainstay of screening for clinically occult disease. Mammography, however, has well-recognized limitations, and recently, other imaging including ultrasound and magnetic resonance imaging have been used as adjunctive screening tools, mainly for women who may be at increased risk for the development of breast cancer. The Society of Breast Imaging and the Breast Imaging Commission of the ACR are issuing these recommendations to provide guidance to patients and clinicians on the use of imaging to screen for breast cancer. Wherever possible, the recommendations are based on available evidence. Where evidence is lacking, the recommendations are based on consensus opinions of the fellows and executive committee of the Society of Breast Imaging and the members of the Breast Imaging Commission of the ACR.

Shear-wave Elastography Improves the Specificity of Breast US: The BE1 Multinational Study of 939 Masses

PURPOSE To determine whether adding shear-wave (SW) elastographic features could improve accuracy of ultrasonographic (US) assessment of breast masses. MATERIALS AND METHODS From September 2008 to September 2010, 958 women consented to repeat standard breast US supplemented by quantitative SW elastographic examination in this prospective multicenter institutional review board-approved, HIPAA-compliant protocol. B-mode Breast Imaging Reporting and Data System (BI-RADS) features and assessments were recorded. SW elastographic evaluation (mean, maximum, and minimum elasticity of stiffest portion of mass and surrounding tissue; lesion-to-fat elasticity ratio; ratio of SW elastographic-to-B-mode lesion diameter or area; SW elastographic lesion shape and homogeneity) was performed. Qualitative color SW elastographic stiffness was assessed independently. Nine hundred thirty-nine masses were analyzable; 102 BI-RADS category 2 masses were assumed to be benign; reference standard was available for 837 category 3 or higher lesions. Considering BI-RADS category 4a or higher as test positive for malignancy, effect of SW elastographic features on area under the receiver operating characteristic curve (AUC), sensitivity, and specificity after reclassifying category 3 and 4a masses was determined. RESULTS Median participant age was 50 years; 289 of 939 (30.8%) masses were malignant (median mass size, 12 mm). B-mode BI-RADS AUC was 0.950; eight of 303 (2.6%) BI-RADS category 3 masses, 18 of 193 (9.3%) category 4a lesions, 41 of 97 (42%) category 4b lesions, 42 of 57 (74%) category 4c lesions, and 180 of 187 (96.3%) category 5 lesions were malignant. By using visual color stiffness to selectively upgrade category 3 and lack of stiffness to downgrade category 4a masses, specificity improved from 61.1% (397 of 650) to 78.5% (510 of 650) (P<.001); AUC increased to 0.962 (P=.005). Oval shape on SW elastographic images and quantitative maximum elasticity of 80 kPa (5.2 m/sec) or less improved specificity (69.4% [451 of 650] and 77.4% [503 of 650], P<.001 for both), without significant improvement in sensitivity or AUC. CONCLUSION Adding SW elastographic features to BI-RADS feature analysis improved specificity of breast US mass assessment without loss of sensitivity.

Computerized lesion detection on breast ultrasound

We investigated the use of a radial gradient index (RGI) filtering technique to automatically detect lesions on breast ultrasound. After initial RGI filtering, a sensitivity of 87% at 0.76 false-positive detections per image was obtained on a database of 400 patients (757 images). Next, lesion candidates were segmented from the background by maximizing an average radial gradient (ARD) index for regions grown from the detected points. At an overlap of 0.4 with a radiologist lesion outline, 75% of the lesions were correctly detected. Subsequently, round robin analysis was used to assess the quality of the classification of lesion candidates into actual lesions and false-positives by a Bayesian neural network. The round robin analysis yielded an Az value of 0.84, and an overall performance by case of 94% sensitivity at 0.48 false-positives per image. Use of computerized analysis of breast sonograms may ultimately facilitate the use of sonography in breast cancer screening programs.

The ACR BI-RADS® Experience: Learning From History

The Breast Imaging Reporting and Data System (BI-RADS) initiative, instituted by the ACR, was begun in the late 1980s to address a lack of standardization and uniformity in mammography practice reporting. An important component of the BI-RADS initiative is the lexicon, a dictionary of descriptors of specific imaging features. The BI-RADS lexicon has always been data driven, using descriptors that previously had been shown in the literature to be predictive of benign and malignant disease. Once established, the BI-RADS lexicon provided new opportunities for quality assurance, communication, research, and improved patient care. The history of this lexicon illustrates a series of challenges and instructive successes that provide a valuable guide for other groups that aspire to develop similar lexicons in the future.

Reasons Women at Elevated Risk of Breast Cancer Refuse Breast MR Imaging Screening: ACRIN 6666

PURPOSE To determine reasons for nonparticipation in a trial of supplemental screening with magnetic resonance (MR) imaging after mammography and ultrasonography (US). MATERIALS AND METHODS Women(n = 2809) at elevated risk of breast cancer were enrolled in the American College of Radiology Imaging Network 6666 US Screening Protocol at 21 institutions. Fourteen institutions met technical and experience requirements for this institutional review board-approved, HIPAA-compliant substudy of supplemental screening with MR imaging. Those women who had completed 0-, 12-, and 24-month screenings with mammography combined with US were considered for a single contrast material-enhanced MR examination within 8 weeks after completing the 24-month mammography-US screening. A total of 1593 women had complete MR substudy registration data: 378 of them were ineligible for the study, and 1215 had analyzable data. Reasons for nonparticipation were determined. Demographic data were compared between study participants and nonparticipants. RESULTS Of 1215 women with analyzable data, 703 (57.9%), with a mean age of 54.8 years, were enrolled in the MR substudy and 512 (42.1%) declined participation. Women with a 25% or greater lifetime risk of breast cancer were more likely to participate (odds ratio, 1.53; 95% confidence interval: 1.10, 2.12). Of 512 nonparticipants, 130 (25.4%) refused owing to claustrophobia; 93 (18.2%), owing to time constraints; 62 (12.1%), owing to financial concerns; 47 (9.2%), because their physician would not provide a referral and/or did not believe MR imaging was indicated; 40 (7.8%), because they were not interested; 39 (7.6%), because they were medically intolerant to MR imaging; 29 (5.7%), because they did not want to undergo intravenous injection; 27 (5.3%), owing to additional biopsy or other procedures that might be required subsequently; 21 (4.1%), owing to MR imaging scheduling constraints; 11 (2.2%), because of the travel required; seven (1.4%), owing to gadolinium-related risks or allergies; and six (1.2%), for unknown reasons. CONCLUSION Of 1215 women with elevated breast cancer risk who could, according to protocol guidelines, undergo breast MR imaging, only 57.9% agreed to participate.

ULTRASOUND AS A COMPLEMENT TO MAMMOGRAPHY AND BREAST EXAMINATION TO CHARACTERIZE BREAST MASSES

This study was designed to determine if complementary ultrasound (US) imaging and Doppler could decrease the number of biopsies for benign masses. A total of 761 breast masses were sequentially scored on a level of suspicion (LOS) of 1-5, where 1 represented low, and 5 was a high suspicion of malignancy, for mammography, US, and color flow with pulse Doppler (DUS). After biopsy, the results were analyzed using 2 x 2 contingency tables and ROC analysis, for mammography alone and in combination with US and DUS. The addition of US increased the specificity from 51.4% to 66.4% at a prevalence of 31.3% malignancy. ROC analysis showed that the addition of US significantly improved the performance over mammography alone in women < 55 years old (p = 0.049); > 55 years old (p = 0.029); masses < 1 cm (p = 0.016) and masses > 1 cm (p = 0.016). These results show that the addition of US to mammography alone could substantially reduce the number of breast biopsies for benign disease.

Computerized detection and classification of cancer on breast ultrasound1

RATIONALE AND OBJECTIVES To develop and evaluate a two-stage computerized method that first detects suspicious regions on ultrasound images, and subsequently distinguishes among different lesion types. MATERIALS AND METHODS The first stage of detecting potential lesions was based on expected lesion shape and margin characteristics. After the detection stage, all candidate lesions were classified by a Bayesian neural net based on computer-extracted lesion features. Two separate tasks were performed and evaluated at the classification stage: the first classification task was the distinction between all actual lesions and false-positive detections; the second classification task was the distinction between actual cancer and all other detected lesion candidates (including false-positive detections). The neural nets were trained on a database of 400 cases (757 images), consisting of complex cysts and benign and malignant lesions, and tested on an independent database of 458 cases (1,740 images including 578 normal images). RESULTS In the distinction between all actual lesions and false-positive detections, Az values of 0.94 and 0.91 were obtained with the training and testing data sets, respectively. Sensitivity by patient of 90% at 0.45 false-positive detections per image was achieved for this detection-plus-classification scheme for the testing data set. Distinguishing cancer from all other detections (false-positives plus all benign lesions) proved to be more challenging, and Az values of 0.87 and 0.81 were obtained during training and testing, respectively. Sensitivity by patient of 100% at 0.43 false-positive malignancies per image was achieved in the detection and classification of cancerous lesions for the testing dataset. CONCLUSION The results show promising performance of the computerized lesion detection and classification method, and indicate the potential of such a system for clinical breast ultrasound.

Atypical lobular hyperplasia and classic lobular carcinoma in situ in core biopsy specimens: routine excision is not necessary

Standardized recommendations for the management of lobular neoplasia in core biopsy specimens are not established. The aim of our study was to define morphologic features of lobular neoplasia in core biopsies that predict the finding of ductal carcinoma in situ or invasive carcinoma in the subsequent excisional specimen. We reviewed 333 cases of atypical lobular hyperplasia or lobular carcinoma in situ without ductal carcinoma in situ or invasive carcinoma diagnosed in core biopsies from 1996 to 2006. Subsequent excision was performed in 41% (136/333) of cases, including atypical lobular hyperplasia (n=48), lobular carcinoma in situ (n=39), and lobular neoplasia associated with atypical ductal hyperplasia (n=49). Upgrades were identified in 2% (1/48) of atypical lobular hyperplasia, 23% (9/39) of lobular carcinoma in situ, and 27% (13/49) of lobular neoplasia associated with atypical ductal hyperplasia cases. When further analyzed, the upgraded cases of lobular carcinoma in situ were associated with radiologic–pathologic discordance in 6/9 cases and with nonclassic pathology (two lobular carcinoma in situ with necrosis and one pleomorphic lobular carcinoma in situ) in the remaining three cases. The frequency of upgrade was 11% (3/26) in classic lobular carcinoma in situ, and 46% (6/13) in nonclassic types (pleomorphic or with necrosis). After excluding cases with discordant imaging/pathology, there was a 5% upgrade in our excisional specimens. After excluding cases where the upgrade was associated with nonclassic morphology, the upgrade in our study was 1%. Our results suggest that atypical lobular hyperplasia and classic lobular carcinoma in situ with concordant radiology and pathology can be appropriately managed with clinical follow-up without surgery.