Contrast-Enhanced Mammography for Women with Palpable Breast Abnormalities.

RATIONALE AND OBJECTIVES: To examine the role of contrast-enhanced mammography (CEM) in the work-up of palpable breast abnormalities. MATERIALS AND METHODS: In this single-center combination prospective-retrospective study, women with palpable breast abnormalities underwent CEM evaluation prospectively, comprising the acquisition of low energy (LE) images and recombined images (RI) which depict enhancement, followed by targeted ultrasound (US). Two independent readers retrospectively reviewed the imaging and assigned BI-RADS assessment based on LE alone, LE plus US, RI with LE plus US (CEM plus US), and RI alone. Pathology results or 1-year follow-up imaging served as the reference standard. RESULTS: 237 women with 262 palpable abnormalities were included (mean age, 51 years). Of the 262 palpable abnormalities, 116/262 (44%) had no imaging correlate and 242/262 (92%) were benign. RI alone had better specificity compared to LE plus US (Reader 1, 94% versus 89% (p = 0.009); Reader 2, 93% versus 88% (p = 0.03)), better positive predictive value (Reader 1, 52% versus 42% (p = 0.04); Reader 2, 53% versus 42% (p = 0.04)), and better accuracy (Reader 1, 93% versus 89% (p = 0.05); Reader 2, 93% versus 90% (p = 0.06)). CEM plus US was not significantly different in performance metrics versus LE plus US. CONCLUSION: RI had better specificity compared to LE in combination with US. There was no difference in performance between CEM plus US and LE plus US, likely reflecting the weight US carries in radiologist decision-making. However, the results indicate that the absence of enhancement on RI in the setting of palpable lesions may help avoid benign biopsies.

Contrast-enhanced mammography: past, present, and future.

Contrast-enhanced mammography (CEM) combines conventional mammography with iodinated contrast material to improve cancer detection. CEM has comparable performance to breast MRI without the added cost or time of conventional MRI protocols. Thus, this technique may be useful for indications previously reserved for MRI, such as problem-solving, determining disease extent in patients with newly diagnosed cancer, monitoring response to neoadjuvant therapy, evaluating the posttreatment breast for residual or recurrent disease, and potentially screening in women at intermediate- or high-risk for breast cancer. This article will provide a comprehensive overview on the past, present, and future of CEM, including its evolving role in the diagnostic and screening settings.

Performance of Dual-Energy Contrast-enhanced Digital Mammography for Screening Women at Increased Risk of Breast Cancer.

BackgroundContrast agent-enhanced digital mammography (CEDM) has been shown to be more sensitive and specific than two-dimensional full-field digital mammography in the diagnostic setting. Few studies have reported on its performance in the screening setting.PurposeTo evaluate the performance of CEDM for breast cancer screening.Materials and MethodsThis retrospective study included women who underwent dual-energy CEDM for breast cancer screening from December 2012 through April 2016. Medical records were reviewed for age, risk factors, short-interval follow-up and biopsies recommended, and cancers detected. Sensitivity, specificity, positive predictive value of abnormal findings at screening (PPV1), positive predictive value of biopsy performed (PPV3), and negative predictive value were determined.ResultsIn the study period 904 baseline CEDMs were performed. Mean age was 51.8 years ± 9.4 (standard deviation). Of 904 patients, 700 (77.4%) had dense breasts, 247 (27.3%) had a family history of breast cancer in a first-degree relative age 50 years or younger, and 363 (40.2%) a personal history of breast cancer. The final Breast Imaging Reporting and Data System score was 1 or 2 in 832 of 904 (92.0%) patients, score of 3 in 25 of 904 (2.8%) patients, and score of 4 or 5 in 47 of 904 (5.2%) patients. By using CEDM, 15 cancers were diagnosed in 14 of 904 women (cancer detection rate, 15.5 of 1000). PPV3 was 29.4% (15 of 51). At least 1-year follow up was available in 858 women. There were two interval cancers. Sensitivity was 50.0% (eight of 16; 95% confidence interval [CI]: 24.7%, 75.3%) on the low-energy images compared with 87.5% (14 of 16; 95% CI: 61.7%, 98.4%) for the entire study (low-energy and iodine images; P = .03). Specificity was 93.7% (789 of 842; 95% CI: 91.8%, 95.2%); PPV1 was 20.9% (14 of 67; 95% CI: 11.9%, 32.6%), and negative predictive value was 99.7% (789 of 791; 95% CI: 99.09%, 99.97%).ConclusionContrast-enhanced digital mammography is a promising technique for screening women with higher-than-average risk for breast cancer.© RSNA, 2019.

Mammographic screening in male patients at high risk for breast cancer: is it worth it?

PURPOSE: To investigate the utility of mammography for breast cancer screening in a population of males at increased risk for breast cancer. METHODS: In this HIPAA-compliant institutional review board-approved single-institution study, mammography records and clinical data of 827 male patients who underwent digital mammography from September 2011-July 2018 were analyzed via the electronic medical record. 664 of these men presented with masses, pain, or nipple discharge and were excluded from this study. The remaining 163 asymptomatic men with familial and/or personal history of breast cancer, or with a known germline mutation in BRCA, underwent screening mammography and were included in this analysis. RESULTS: 163 asymptomatic men (age: mean 63 years, range 24-87 years) underwent 806 screening mammograms. 125/163 (77%) had a personal history of breast cancer and 72/163 (44%) had a family history of breast cancer. 24/163 (15%) were known mutation carriers: 4/24 (17%) BRCA1 and 20/24 (83%) BRCA2. 792/806 (98%) of the screening mammograms were negative (BI-RADS 1 or 2); 10/806 (1.2%) were classified as BI-RADS 3, all of which were eventually downgraded to BI-RADS 2 on follow-up. 4/806 (0.4%) mammograms were abnormal (BI-RADS 4/5): all were malignant. The cancer detection rate in this cohort was 4.9 cancers/1000 examinations. CONCLUSIONS: In our cohort, screening mammography yielded a cancer detection rate of 4.9 cancers/1000 examinations which is like the detection rate of screening mammography in a population of women at average risk, indicating that screening mammography is of value in male patients at high risk for breast cancer.

Calcifications at Digital Breast Tomosynthesis: Imaging Features and Biopsy Techniques.

Full-field digital mammography (FFDM), the standard of care for breast cancer screening, has some limitations. With the advent of digital breast tomosynthesis (DBT), improvements including decreased recall rates and increased cancer detection rates have been observed. The quasi-three-dimensional capability of DBT reduces breast tissue overlap, a significant limitation of FFDM. However, early studies demonstrate that a few cancers detected at FFDM may not be diagnosed at DBT-only screening, and lesions with calcifications as the dominant feature may look less suspicious at DBT or not be visible at all. These findings support the use of combined FFDM and DBT protocols to optimize screening performance. However, this combination would approximately double the patient's radiation exposure. The development of computer algorithms that generate two-dimensional synthesized mammography (SM) views from DBT has improved calcification conspicuity and sensitivity. Therefore, SM may substitute for FFDM in screening protocols, reducing radiation exposure. DBT plus SM demonstrates significantly better performance than that of FFDM alone, although there are reports of missed malignant calcifications. Thus, some centers continue to perform FFDM with DBT. Use of DBT in breast imaging has also necessitated the development of DBT-guided biopsy. DBT-guided biopsy may have a higher success rate than that of stereotactic biopsy, with a shorter procedure time. While DBT brings substantial improvements to breast cancer imaging, it is important to be aware of its strengths and limitations regarding detection of calcifications. This article reviews the imaging appearance of breast calcifications at DBT, discusses calcification biopsy techniques, and provides an overview of the current literature. Online supplemental material is available for this article. ©RSNA, 2019 An earlier incorrect version of this article appeared online. This article was corrected on February 13, 2019.

Differences in degree of lesion enhancement on CEM between ILC and IDC.

OBJECTIVE: To investigate differences in the degree of enhancement on contrast-enhanced mammography (CEM) between patients with invasive lobular (ILC) and infiltrating ductal carcinoma (IDC) not otherwise specified. METHODS AND MATERIALS: Between 2010 and 2017, all patients diagnosed with ILC and who underwent CEM were included for this dual center study. Twenty-two patients with IDC, matched by size, were identified for comparison. Three independent readers, blinded for histopathology results, re-evaluated all CEM exams to determine degree of lesion enhancement according to a previously defined scoring scale ranging from minimal to strong enhancement. Interobserver agreement among the three readers was calculated by quadratic weighted κ coefficient. RESULTS: 44 patients were included: 22 patients with ILC and 22 patients with IDC. There were no significant differences in age, mean tumor size, tumor grade or receptor status between the two subgroups. Degree of lesion enhancement on CEM was more often considered weak in case of ILC compared to IDC according to two out of three readers (31.8% vs 4.5 %, p = 0.045 and 22.7 vs 4.5 %, p = 0.185). All other lesions showed moderate or strong enhancement. Interobserver agreement between the three independent readers was good (κ = 0.72). CONCLUSION: In patients with ILC, degree of lesion enhancement on CEM appears to be more often weak than in infiltrating ductal carcinoma not otherwise specified. Radiologists should be aware that weakly enhancing lesions may in fact be malignant and particularly invasive lobular cancers. ADVANCES IN KNOWLEDGE: Three independent readers evaluated 44 CEM cases with ILC or IDC. Degree of lesion enhancement seems more often weak in case of ILC. Radiologists should be aware of ILC in case of weak CEM enhancement.

Calling all calcifications: a retrospective case control study.

INTRODUCTION: The majority of recalls from screening mammography do not result in biopsy recommendation. The purpose of this study was to evaluate if calcifications recalled from screening mammography are more likely to result in biopsy recommendations than other findings. METHODS: IRB-approved electronic medical record search was performed to obtain a random sample of screening mammograms assigned BI-RADS 0 assessment during 2014-2015. Primary reason for recall was classified as mass, asymmetry, focal asymmetry, calcifications, or distortion. Primary outcome was biopsy performed after diagnostic work-up. Secondary outcome was proportion of biopsies performed that were positive for cancer, positive predictive value 3 (PPV3). Logistic regression was used to compare reasons for recall (calcifications vs other findings) with biopsy recommendation proportions. RESULTS: Random database sampling yielded 402 screening examinations with BI-RADS 0 assessments with 449 total findings. Reasons for recall included calcifications (14.0%, 63/449), masses (15.8%, 71/449), asymmetries (50.8%, 228/449), focal asymmetries (14.3%, 64/449) and architectural distortions (5.1%, 23/449). Overall, 21.6% of recalls led to image-guided biopsy (87/402). Recalls for calcifications were more likely to result in biopsy compared with other types of findings (Adjusted OR 8.56, 95% CI 4.58 to 16.0, p < 0.001). No statistically significant differences were found in PPV3 proportions between calcification and non-calcification findings (p = 0.812). CONCLUSION: Recalls for calcifications are much more likely to undergo biopsy compared with other findings. Increased biopsy rates for calcifications should be considered when recalling a patient from mammography screening in the context of practice specific positive predictive values and cancer detection rates.

The Impact of Patient-Initiated Subspecialty Review on Patient Care.

PURPOSE: To determine the effect of subspecialty review of breast imaging on patients without a diagnosis of breast cancer who self-referred for a second opinion. METHODS: Institutional review board-approved retrospective review was performed of 415 breast imaging studies submitted to our cancer center for second-opinion review by 245 patients in 2014, excluding cases without follow-up or change in original BI-RADS 0 assessment. One hundred forty-seven patients with 176 lesions were included. Original and second-opinion interpretations and recommendations were compared with histopathology or follow-up imaging. RESULTS: Ninety-six of 176 (55%) lesions were reported as suspicious in the original interpretation. Second-opinion review was discordant with the original interpretation in 82 of 176 (47%) lesions. Second-opinion review downgraded 24 of 96 (25%) lesions originally reported as suspicious to benign or probably benign, averting biopsy of these lesions. Second-opinion review upgraded 31 of 80 (39%) lesions originally reported as benign or probably benign to suspicious. A total of 87 lesions were biopsied yielding malignancy in 23 (26%) biopsies. Twenty-eight of 87 (32%) biopsies performed were recommended after second-opinion review, with 8 of 28 (29%) of these biopsies yielding cancer. Eight of 23 (35%) cancers detected represented malignancy not initially detected in the original interpretation. CONCLUSION: Second-opinion review is valuable in patients pursuing a breast imaging specialist's opinion, even before they are diagnosed with breast cancer. Second-opinion review disagreed with the original interpretation for 47% of lesions, averted 25% of originally recommended biopsies, and detected cancer in 29% of additional biopsies recommended. Thirty-five percent of cancers diagnosed after second-opinion review were not initially detected in the original interpretation.

Histopathologic characteristics of background parenchymal enhancement (BPE) on breast MRI.

PURPOSE: Breast fibroglandular tissue (FGT), as visualized on a mammogram (mammographic density, MD), is one of the strongest known risk factors for breast cancer. FGT is also visible on breast MRI, and increased background parenchymal enhancement (BPE) in the FGT has been identified as potentially a major breast cancer risk factor. The aim of this exploratory study was to examine the biologic basis of BPE. METHODS: We examined the unaffected contra-lateral breast of 80 breast cancer patients undergoing a prophylactic mastectomy before any treatment other than surgery of their breast cancer. BPE was classified on the BI-RADS scale (minimal/mild/moderate/marked). Slides were stained for microvessel density (MVD), CD34 (another measure of endothelial density), glandular tissue within the FGT and VEGF. Spearman correlations were used to evaluate the associations between BPE and these pathologic variables. RESULTS: In pre-menopausal patients, BPE was highly correlated with MVD, CD34 and glandular concentration within the FGT, and the pathologic variables were themselves highly correlated. The expression of VEGF was effectively confined to terminal duct lobular unit (TDLU) epithelium. The same relationships of the four pathologic variables with BPE were seen in post-menopausal patients, but the relationships were much weaker and not statistically significant. CONCLUSION: The strong correlation of BPE and MVD together with the high correlation of MVD with glandular concentration seen in pre-menopausal patients indicates that increased breast cancer risk associated with BPE in pre-menopausal women is likely to result from its association with increased concentration of glandular tissue in the FGT. The effective confinement of VEGF expression to the TDLUs shows that the signal for MVD growth arises directly from the glandular tissue. Further studies are needed to understand the basis of BPE in post-menopausal women.

Second-Opinion Review of Breast Imaging at a Cancer Center: Is It Worthwhile?

OBJECTIVE: Second-opinion review of breast imaging studies can be a time-consuming and labor-intensive process. The purpose of this investigation was to determine whether reinterpretation of studies obtained at institutions outside a cancer center influences clinical management, specifically by revealing additional cancer and preventing unnecessary biopsy. MATERIALS AND METHODS: A review was conducted of breast imaging studies of 200 patients who underwent ultrasound and MRI at community facilities and had the images submitted for second opinions at a cancer center between January and April 2014. Each case was evaluated for concordance between the original report and the second-opinion interpretation. Second-opinion review resulting in the recommendation and performance of new biopsies was further subdivided into benign, high-risk, and malignant categories based on the histopathologic results obtained at the cancer center. RESULTS: Second-opinion review of the 200 cases showed a change in interpretation in 55 cases (28%; 95% CI, 21-34%). Overall, 26 recommendations (13%; 95% CI, 9-18%) led to a major change in management. Twenty new biopsies were performed, yielding 10 malignancies (5%; 95% CI, 2-9%) and four high-risk lesions (2%; 95% CI, 1-5%). Surgical management was changed to mastectomy for 6 of 10 patients (60%) with new sites of biopsy-proven malignancy. Eight biopsies were averted (4%; 95% CI, 2-8%) on the basis of benign interpretation of the imaging findings, and no disease was found at 1-year follow-up evaluation. CONCLUSION: Reinterpretation of studies obtained outside a cancer center resulted in a change in interpretation in more than one-fourth of submitted studies. Additional cancer was detected in 5% of patients, and biopsy was averted for 4%. The practice of second-opinion review influences clinical management and adds value to patient care.

Clinical breast examination in a comprehensive breast cancer screening program: contribution and cost.

PURPOSE: To retrospectively evaluate the cost of clinical breast examination (CBE) and its contribution to screening mammography in the detection of breast cancer. MATERIALS AND METHODS: The study received a waiver of authorization from the institutional review board, informed patient consent was not required, and the study was compliant with HIPAA regulations. The records of 60 027 consecutive asymptomatic patients who underwent screening mammography were retrospectively reviewed. CBE was performed on all patients by a nurse practitioner. Patients with positive CBE findings were required to convert from screening to diagnostic evaluation; the number of cancer diagnoses that resulted was determined. The reports, four-view mammograms, or both of patients requiring conversion to diagnostic evaluation were reviewed to determine those patients likely to undergo diagnostic imaging on the basis of screening mammographic findings alone. The cost of CBE was calculated and divided by the number of cancers detected solely with CBE to determine the cost of CBE per additional cancer detected. RESULTS: Four hundred seventy-four (age range, 32-95) of 60 027 asymptomatic patients had positive CBE findings which required conversion to diagnostic evaluation. Forty-six cancers in 44 patients were subsequently diagnosed; 32 would have been detected with mammography alone, whereas 14 were imperceptible at screening mammography. The cost of CBE was $122 598 per cancer detected solely with positive CBE findings. CONCLUSION: CBE performed by nurse practitioners led to the diagnosis of 14 cancers in 13 patients with mammographically occult tumors (0.02% of the screening population and approximately 3% of all cancers diagnosed at the facility during this study). The cost of detecting these additional cancers is estimated to be $122 598 per cancer.

Mammary hibernoma.

We report the case of a 39-year-old asymptomatic woman who presented for screening mammography. Mammography revealed a round, partially circumscribed, partially indistinct, noncalcified 4.5 cm mass in upper outer right breast. This vaguely palpable mass appeared as a well-circumscribed, oval, hyperechoic, parallel, septated mass on sonography. Ultrasound-guided core biopsy led to the diagnosis of hibernoma. Few cases of hibernomas have been reported in the English literature, and their occurrence in the breast is particularly rare [Eur J Surg Oncol 26 (2000) 430; Am J Surg Pathol 25 (2001) 809]. To our knowledge, this is the first case of mammary hibernoma in which the ultrasonographic and mammographic features of this unusual entity are demonstrated.