Mary C. Mahoney

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.

ACR Appropriateness Criteria Breast Cancer Screening

Mammography is the recommended method for breast cancer screening of women in the general population. However, mammography alone does not perform as well as mammography plus supplemental screening in high-risk women. Therefore, supplemental screening with MRI or ultrasound is recommended in selected high-risk populations. Screening breast MRI is recommended in women at high risk for breast cancer on the basis of family history or genetic predisposition. Ultrasound is an option for those high-risk women who cannot undergo MRI. Recent literature also supports the use of breast MRI in some women of intermediate risk, and ultrasound may be an option for intermediate-risk women with dense breasts. There is insufficient evidence to support the use of other imaging modalities, such as thermography, breast-specific gamma imaging, positron emission mammography, and optical imaging, for breast cancer screening. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

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.

Granular Cell Tumor of the Breast: A Series of 17 Cases and Review of the Literature

Abstract:  Seventeen cases of granular cell tumor (GCT) of the breast are reviewed. The demographics and clinical features are reviewed and the radiologic and pathologic features as well as the immunohistochemistry are discussed. To our knowledge, our series of 17 breast GCT cases represent the largest series published to date. 

Positive Predictive Value of BI-RADS MR Imaging

PURPOSE To evaluate the positive predictive values (PPVs) of Breast Imaging and Reporting Data Systems (BI-RADS) assessment categories for breast magnetic resonance (MR) imaging and to identify the BI-RADS MR imaging lesion features most predictive of cancer. MATERIALS AND METHODS This institutional review board-approved HIPAA-compliant prospective multicenter study was performed with written informed consent. Breast MR imaging studies of the contralateral breast in women with a recent diagnosis of breast cancer were prospectively evaluated. Contralateral breast MR imaging BI-RADS assessment categories, morphologic descriptors for foci, masses, non-masslike enhancement (NMLE), and kinetic features were assessed for predictive values for malignancy. PPV of each imaging characteristic of interest was estimated, and logistic regression analysis was used to examine the predictive ability of combinations of characteristics. RESULTS Of 969 participants, 71.3% had a BI-RADS category 1 or 2 assessment; 10.9%, a BI-RADS category 3 assessment; 10.0%, a BI-RADS category 4 or 5 assessment; and 7.7%, a BI-RADS category 0 assessment on the basis of initial MR images. Thirty-one cancers were detected with MR imaging. Overall PPV for BI-RADS category 4 and 5 lesions was 0.278, with 17 cancers in patients with a BI-RADS category 4 lesion (PPV, 0.205) and 10 cancers in patients with a BI-RADS category 5 lesion (PPV, 0.714). Of the cancers, one was a focus, 17 were masses, and 13 were NMLEs. For masses, irregular shape, irregular margins, spiculated margins, and marked internal enhancement were most predictive of malignancy. For NMLEs, ductal, clumped, and reticular or dendritic enhancement were the features most frequently seen with malignancy. Kinetic enhancement features were less predictive of malignancy than were morphologic features. CONCLUSION Standardized terminology of the BI-RADS lexicon enables quantification of the likelihood of malignancy for MR imaging-detected lesions through careful evaluation of lesion features. In particular, BI-RADS assessment categories and morphologic descriptors for masses and NMLE were useful in estimating the probability of cancer.

Lobular Neoplasia at 11-Gauge Vacuum-Assisted Stereotactic Biopsy: Correlation with Surgical Excisional Biopsy and Mammographic Follow-Up

OBJECTIVE The objective of our study was to evaluate the outcome of lobular neoplasia diagnosed at 11-gauge stereotactic vacuum-assisted biopsy (SVAB). MATERIALS AND METHODS Retrospective review of 1,819 lesions sampled with 11-gauge SVAB yielded 27 patients with lobular neoplasia as the most severe pathologic entity diagnosed. Patients with lobular neoplasia associated with atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or infiltrating carcinoma were excluded. Twenty patients underwent surgical excisional biopsy, and seven patients were followed mammographically for a mean of 52 months (range, 14-67 months). Mammographic lesion type, number of specimens obtained per lesion, and specific histologic features related to lobular carcinoma in situ (LCIS) were assessed. Results were compared with histologic findings at surgery or mammographic follow-up. RESULTS Nineteen lesions presented mammographically as microcalcifications, four as masses, three as masses with associated microcalcifications, and one as architectural distortion. A mean of 13 specimens were obtained per lesion. Carcinoma was found at surgical excision in 19% of the lesions (5/27). Lesions were upgraded to DCIS (n = 2), invasive lobular carcinoma (n = 2), and mixed invasive ductal and lobular carcinoma (n = 1). In addition to the diagnosis of lobular neoplasia at SVAB, one patient presented with synchronous infiltrating ductal carcinoma in the contralateral breast, and two patients developed metachronous infiltrating ductal carcinoma in a different quadrant of the ipsilateral breast. Twelve of the 27 lesions included LCIS. These lesions were evaluated pathologically to distinguish the classic (10/12) from the pleomorphic (2/12) form of this entity. Ten of the 12 LCIS cases underwent surgical excisional biopsy with four of the five upgrades occurring in these patients. Only one of these patients was shown to have the pleomorphic type of LCIS. Lesions in seven patients who underwent mammographic follow-up remained stable. CONCLUSION The known association of lobular neoplasia with high-risk and malignant lesions at surgical biopsy requires careful consideration when lobular neoplasia is diagnosed as the most severe histologic entity at SVAB. The diagnosis of lobular neoplasia at 11-gauge SVAB is not reliable in view of the 19% upgrade rate at the time of surgical excisional biopsy in our study. No predictive mammographic features allowed distinction between the patients with lesions that were upgraded at the time of surgery from those whose lesions were not upgraded.

The BI-RADS Breast Magnetic Resonance Imaging Lexicon

The Breast Magnetic Resonance Imaging Lexicon was designed to standardize interpretation and reporting of breast magnetic resonance (MR) imaging findings, ultimately improving communication between radiologists and clinicians and facilitating patient care. The lexicon includes 3 lesion types: mass, focus, and non-masslike enhancement. The mass category is analogous to the mass category in the mammography lexicon. Non-masslike enhancement is comparable with calcifications in the mammography lexicon. Unique to the MR lexicon is description of lesion enhancement. In addition, description of background enhancement allows assessment and communication of the sensitivity of the study. The Breast MR Imaging Lexicon is reviewed and images provided to illustrate these descriptor terminologies.

Use of BI-RADS 3–Probably Benign Category in the American College of Radiology Imaging Network Digital Mammographic Imaging Screening Trial

PURPOSE To determine (a) how often the Breast Imaging Reporting and Data System (BI-RADS) category 3 was used in the American College of Radiology Imaging Network (ACRIN) Digital Mammographic Imaging Screening Trial (DMIST), either at the time of screening mammography or after work-up, (b) how often subjects actually returned for the recommended follow-up examination, and (c) the rate and stages of any malignancies subsequently found in subjects for whom short-term interval follow-up was recommended. MATERIALS AND METHODS This study was approved by the Institutional Review Board at all institutions where subjects were enrolled. All subjects participating in DMIST gave informed consent and the study was HIPAA-compliant. A total of 47,599 DMIST-eligible and evaluable subjects, all of whom consented to undergo both digital and screen-film mammography, were included in this analysis. Cases referred for short-term interval follow-up based on digital, screen-film, or both imaging examinations were determined. Compliance with the recommendations and the final outcome (malignancy diagnosis at biopsy or no malignancy confirmed through follow-up) of each evaluable case were determined. RESULTS A total of 1114 of the 47,599 (2.34%) subjects had tumors assigned a BI-RADS 3 category and were recommended to undergo short-interval follow-up. In this study, 791 of 1114 (71%) of the subjects were compliant with the recommendation and returned for short-interval follow-up. Of the women who did not return for short-interval follow-up, 70% (226 of 323) did return for their next annual mammography. Among all subjects whose tumors were assigned a BI-RADS 3 category either at screening mammography or after additional work-up, nine of 1114 (0.81%) were found to have cancer. Of the nine biopsy-proved cancers, six were invasive cancers and three were ductal carcinoma in situ stage Tis-T1c. The invasive cancers were all less than 2 cm in size. CONCLUSION In DMIST, radiologists used the BI-RADS 3 classification infrequently (2.3% of patients). Tumors assigned a BI-RADS 3 category had a low rate of malignancy. The relatively high rate of noncompliance with short-interval follow-up recommendations (323 of 1114, or 29%) supports prior recommendations that radiologists thoroughly evaluate lesions before placing them in this category.

Initial clinical experience with a new MRI vacuum‐assisted breast biopsy device

To report initial clinical experience with a new previously unreported vacuum‐assisted device (EnCor MR, SenoRx, Aliso Viejo, CA) for magnetic resonance imaging (MRI)‐guided breast biopsy and to compare this device with previously reported technologies.