Rubina M. Trimboli

Breast Cancer Detection Using Double Reading of Unenhanced MRI Including T1-Weighted, T2- Weighted STIR, and Diffusion- Weighted Imaging: A Proof of Concept Study

OBJECTIVE The purpose of this study was to investigate the diagnostic performance of unenhanced MRI in detecting breast cancer and to assess the impact of double reading. MATERIALS AND METHODS A total of 116 breasts of 67 women who were 36-89 years old were studied at 1.5 T using an unenhanced protocol including axial T1-weighted gradient-echo, T2-weighted STIR, and echo-planar diffusion-weighted imaging (DWI). Two blinded readers (R1 and R2) independently evaluated unenhanced images using the BIRADS scale. A combination of pathology and negative follow-up served as the reference standard. McNemar and kappa statistics were used. RESULTS Per-breast cancer prevalence was 37 of 116 (32%): 30 of 37 (81%) invasive ductal carcinoma, five of 37 (13%) ductal carcinoma in situ, and two of 37 (6%) invasive lobular carcinoma. Per-breast sensitivity of unenhanced MRI was 29 of 37 (78%) for R1, 28 of 37 (76%) for R2, and 29 of 37 (78%) for double reading. Specificity was 71 of 79 (90%) for both R1 and R2 and 69 of 79 (87%) for double reading. Double reading did not provide a significant increase in sensitivity. Interobserver agreement was almost perfect (Cohen κ = 0.873). CONCLUSION An unenhanced breast MRI protocol composed of T1-weighted gradient echo, T2-weighted STIR, and echo-planar DWI enabled breast cancer detection with sensitivity of 76-78% and specificity of 90% without a gain in sensitivity from double reading.

Contrast enhanced breast MRI: Spatial displacement from prone to supine patient's position. Preliminary results

OBJECTIVE To estimate the spatial displacement of breast lesions and nipples in MR images when the patient is moved from the standard prone to a supine position close to ultrasound (US) or surgical setting. MATERIALS AND METHODS Eleven patients underwent breast MRI in prone position with dynamic 3D T1-weighted sequences using 0.1 mmol/kg gadobenate dimeglumine. Subsequently, the patient was repositioned in supine position and a 3D volumetric interpolated breathhold examination sequence was acquired using a thoracic surface coil. For both positions we measured the following minimal distances: (A) from lesion margin to the coronal plane passing through the anterior surface of the sternum, antero-posterior, on native axial images; (B) from lesion margin to the medial sagittal plane, on native axial images, latero-medial; (C) from lesion margin to the axial plane passing through the tracheal bifurcation, cranio-caudal; (D) from lesion margin to the thoracic wall/pectoral muscle, on native axial images; (E) from lesion margin to the skin, on native axial images; (F) from lesion margin to the base of the nipple, on oblique reconstructions. Measurements from A to D were also obtained for each nipple. The prone-to-supine spatial displacement was calculated as the absolute difference between the measurement obtained in supine position and the same measurement obtained in prone position. Displacements were presented as mean ± standard deviation and median in parenthesis. RESULTS Lesion displacements were (mm): A = 60 ± 38 (55); B = 40 ± 26 (41); C = 41 ± 33 (34); D = 32 ± 31 (27); E = 6 ± 5 (7); and F = 8 ± 6 (7). Nipple displacements were (mm): A = 84 ± 44 (91); B = 54 ± 24 (56); C = 27 ± 15 (24); and D = 48 ± 20 (48). CONCLUSION These preliminary results show that preoperative breast MRI in prone position implies a median lesion displacement of about 3-6 cm along the three orthogonal directions in comparison with supine MRI. Conversely, median lesion-to-skin and lesion-to-nipple displacements were less than 1cm, even though nipple displacements were similar to or larger than those of lesions. The lesion-to-nipple distance may be the most reliable measure to be used for second look breast US. Larger studies are warranted in order to define an optimized breast MRI protocol in the preoperative setting.

Breast MRI Using a High-Relaxivity Contrast Agent: An Overview

OBJECTIVE The purpose of this article is to review the use of gadobenate dimeglumine, a high-relaxivity gadolinium-based contrast material, for breast MRI. CONCLUSION Thanks to its high relaxivity, gadobenate dimeglumine offers valuable advantages in terms of lesion conspicuity, detection rate, and sensitivity for malignant breast lesions. However, a higher enhancement of benign lesions should be taken into account to avoid reduced specificity.

MR Imaging for Selection of Patients for Partial Breast Irradiation: A Systematic Review and Meta-Analysis

PURPOSE To systematically review articles that estimated the ineligibility for partial breast irradiation (PBI) after magnetic resonance (MR) imaging. MATERIALS AND METHODS No ethics committee approval was needed. A systematic search was performed by using MEDLINE and EMBASE. The rate of patients eligible at standard assessment (ie, clinical examination, mammography, and/or ultrasonography) but ineligible after MR imaging was a study outcome. Odds ratios (ORs) were calculated to identify predictors. Quality was appraised by using the Strengthening Reporting of Observational Studies in Epidemiology checklist. RESULTS Of 93 retrieved articles, six were included (total, 3136 patients). For PBI eligibility, all studies applied National Surgical Adjuvant Breast and Bowel Project B-39 criteria. Ineligibility at standard assessment varied from 21% to 80%; MR imaging prompted ineligibility for PBI in 6%-25% of patients who were initially deemed eligible or in 2%-20% if calculated on the overall number of patients initially screened. Meta-regression showed a negative correlation between ineligibility at standard assessment and ineligibility after MR imaging (P < .001). The pooled percentage of patients eligible at standard assessment but ineligible after MR imaging was 11% (95% confidence interval [CI]: 6%, 19%). Predictors for ineligibility after MR imaging were cancers stage pT2 or greater versus less than stage pT2 (OR, 8.8 [95% CI: 4.7, 16.7]; P < .001), invasive lobular histopathologic results versus invasive ductal pathologic results (OR, 3.0 [95% CI: 1.6, 6.6]; P = .007), pre- versus postmenopausal status (OR, 1.9 [95% CI: 1.3, 2.6]; P < .001), invasive cancer versus ductal carcinoma in situ (OR, 1.6 [95% CI: 1.0, 2.4]; P = .031). Study quality ranged from 17 to 20 (maximum quality, 22). The risk of publication bias was moderate. CONCLUSION One of nine women (11%), who on the sole basis of standard assessment were candidates to undergo PBI, was found to be ineligible after undergoing MR imaging. Breast MR imaging should be used to select patients for PBI.

Impact on the recall rate of digital breast tomosynthesis as an adjunct to digital mammography in the screening setting. A double reading experience and review of the literature

OBJECTIVES To estimate the impact on recall rate (RR) of digital breast tomosynthesis (DBT) associated with digital mammography (DM+DBT), compared to DM alone, evaluate the impact of double reading (DR) and review the literature. METHODS Ethics committees approved this multicenter study. Patients gave informed consent. Women recalled from population-based screening reading were included. Reference standard was histology and/or ≥ 1 year follow up. Negative multiple assessment was considered for patients lost at follow up. Two blinded readers (R1, R2) evaluated first DM and subsequently DM+DBT. RR, sensitivity, specificity, accuracy, positive and negative predictive values (PPV, NPV), were calculated for R1, R2, and DR. Cohen κ and χ(2) were used for R1-R2 agreement and RR related to breast density. RESULTS We included 280 cases (41 malignancies, 66 benign lesions, and 173 negative examinations). The RR reduction was 43% (R1), 58% (R2), 43% (DR). Sensitivity, specificity, accuracy, PPV and NPV were: 93%, 67%, 71%, 33%, 98% for R1; 88%, 73%, 75%, 36%, 97% for R2; 98%, 55%, 61%, 27%, 99% for DR. The agreement was higher for DM+DBT (κ=0.459 versus κ=0.234). Reduction in RR was independent from breast density (p=0.992). CONCLUSION DBT was confirmed to reduce RR, as shown by 13 of 15 previous studies (reported reduction 6-82%, median 31%). This reduction is confirmed when using DR. DBT allows an increased inter-reader agreement.

Mammography: an update of the EUSOBI recommendations on information for women

This article summarises the information to be offered to women about mammography. After a delineation of the aim of early diagnosis of breast cancer, the difference between screening mammography and diagnostic mammography is explained. The need to bring images and reports from the previous mammogram (and from other recent breast imaging examinations) is highlighted. Mammography technique and procedure are described with particular attention to discomfort and pain experienced by a small number of women who undergo the test. Information is given on the recall during a screening programme and on the request for further work-up after a diagnostic mammography. The logic of the mammography report and of classification systems such as R1-R5 and BI-RADS is illustrated, and brief but clear information is given about the diagnostic performance of the test, with particular reference to interval cancers, i.e., those cancers that are missed at screening mammography. Moreover, the breast cancer risk due to radiation exposure from mammography is compared to the reduction in mortality obtained with the test, and the concept of overdiagnosis is presented with a reliable estimation of its extent. Information about new mammographic technologies (tomosynthesis and contrast-enhanced spectral mammography) is also given. Finally, frequently asked questions are answered.Key Points• Direct digital mammography should be preferred to film-screen or phosphor plates.• Screening (in asymptomatic women) should be distinguished from diagnosis (in symptomatic women).• A breast symptom has to be considered even after a negative mammogram.• Digital breast tomosynthesis increases cancer detection and decreases the recall rate.• Contrast-enhanced spectral mammography can help in cancer detection and lesion characterisation.

Triple negative versus non-triple negative breast cancers in high-risk women: Phenotype features and survival from the HIBCRIT-1 MRI-including screening study

Purpose: To compare phenotype features and survival of triple-negative breast cancers (TNBC) versus non-TNBCs detected during a multimodal annual screening of high-risk women. Experimental Design: Analysis of data from asymptomatic high-risk women diagnosed with invasive breast cancer during the HIBCRIT-1 study with median 9.7-year follow-up. Results: Of 501 enrolled women with BRCA1/2 mutation or strong family history (SFH), 44 were diagnosed with invasive breast cancers: 20 BRCA1 (45%), 9 BRCA2 (21%), 15 SFH (34%). Magnetic resonance imaging (MRI) sensitivity (90%) outperformed that of mammography (43%, P < 0.001) and ultrasonography (61%, P = 0.004). The 44 cases (41 screen-detected; 3 BRCA1-associated interval TNBCs) comprised 14 TNBCs (32%) and 30 non-TNBCs (68%), without significant differences for age at diagnosis, menopausal status, prophylactic oophorectomy, or previous breast cancer. Of 14 TNBC patients, 11 (79%) were BRCA1; of the 20 BRCA1 patients, 11 (55%) had TNBC; and of 15 SFH patients, 14 (93%) had non-TNBCs (P = 0.007). Invasive ductal carcinomas (IDC) were 86% for TNBCs versus 43% for non-TNBCs (P = 0.010), G3 IDCs 71% versus 23% (P = 0.006), size 16 ± 5 mm versus 12 ± 6 mm (P = 0.007). TNBC patients had more frequent ipsilateral mastectomy (79% vs. 43% for non-TNBCs, P = 0.050), contralateral prophylactic mastectomy (43% vs. 10%, P = 0.019), and adjuvant chemotherapy (100% vs. 44%, P < 0.001). The 5-year overall survival was 86% ± 9% for TNBCs versus 93% ± 5% (P = 0.946) for non-TNBCs; 5-year disease-free survival was 77% ± 12% versus 76% ± 8% (P = 0.216). Conclusions: In high-risk women, by combining an MRI-including annual screening with adequate treatment, the usual reported gap in outcome between TNBCs and non-TNBCs could be reduced. Clin Cancer Res; 22(4); 895–904. ©2015 AACR.

Clinical Breast MR Using MRS or DWI: Who Is the Winner?

Magnetic resonance imaging (MRI) of the breast gained a role in clinical practice thanks to the optimal sensitivity of contrast-enhanced (CE) protocols. This approach, first proposed 30 years ago and further developed as bilateral highly spatially resolved dynamic study, is currently considered superior for cancer detection to any other technique. However, other directions than CE imaging have been explored. Apart from morphologic features on unenhanced T2-weighted images, two different non-contrast molecular approaches were mainly run in vivo: proton MR spectroscopy (1H-MRS) and diffusion-weighted imaging (DWI). Both approaches have shown aspects of breast cancer (BC) hidden to CE-MRI: 1H-MRS allowed for evaluating the total choline peak (tCho) as a biomarker of malignancy; DWI showed that restricted diffusivity is correlated with high cellularity and tumor aggressiveness. Secondary evidence on the two approaches is now available from systematic reviews and meta-analyses, mainly considered in this article: pooled sensitivity ranged 71–74% for 1H-MRS and 84–91% for DWI; specificity 78–88% and 75–84%, respectively. Interesting research perspectives are opened for both techniques, including multivoxel MRS and statistical strategies for classification of MR spectra as well as diffusion tensor imaging and intravoxel incoherent motion for DWI. However, when looking at a clinical perspective, while MRS remained a research tool with important limitations, such as relatively long acquisition times, frequent low quality spectra, difficult standardization, and quantification of tCho tissue concentration, DWI has been integrated in the standard clinical protocols of breast MRI and several studies showed its potential value as a stand-alone approach for BC detection.

Gadobutrol-Enhanced Magnetic Resonance Imaging of the Breast in the Preoperative Setting: Results of 2 Prospective International Multicenter Phase III Studies.

ObjectivesThe aim of this study was to evaluate the diagnostic efficacy of gadobutrol enhanced preoperative breast magnetic resonance imaging (MRI) in 2 prospective studies. Materials and MethodsApproval of ethics committees and informed consent from patients were obtained. Both Gadobutrol-Enhanced MR Mammography (GEMMA) trials followed a standardized protocol using 1.5 T scanners. After unenhanced scans, patients received 0.1 mmol/kg of gadobutrol for the dynamic study. Six independent blinded readers, 3 for GEMMA1 and 3 for GEMMA2, assessed unenhanced images and, 2 or more weeks apart, contrast-enhanced plus unenhanced breast MRI images (CE-BMRI), using a standard 5-region scheme. Another 6 independent readers (3 for each study) evaluated mammograms alone. Sensitivity was calculated taking into account the identification of regions harboring malignancies (within-patient sensitivity), whereas specificity was based on cancer-free breasts. The first patient from each center was used for site qualification and blinded reader training and excluded from the efficacy analyses. Reference standard was pathology for regions harboring malignancy and a combination of negative pathology, mammography, and ultrasound for cancer-free regions. ResultsOf 906 breast cancer patients enrolled in 13 countries in the 2 studies, 865 received gadobutrol and 787 were evaluated for diagnostic performance (390 in GEMMA1 and 397 in GEMMA2). Within-patient sensitivity, that is, the detection rate of malignant disease extent per patient, ranged from 80% to 89% for CE-BMRI and was significantly superior to unenhanced breast MRI alone (37%–73%) and to mammography alone (68%–73%) for all readers in both trials. Specifity of the CE-BMRI ranged from 83% to 95%. ConclusionIn a very large multicenter preoperative setting, gadobutrol-enhanced breast MRI demonstrated high levels of sensitivity and specificity, consistent with published data on breast MRI.

Preoperative MRI: Did randomized trials conclude the debate?

Breast cancer remains a worldwide big killer also in countries with a long tradition of screening mammography [1]. Multifocal and multicentric nature of breast cancer has been widely demonstrated with a rate of ipsilateral additional cancers on histology up to 60% [2,3]. The annual risk for metachronous contralateral cancer in women with a previous history of breast cancer is 0.4–0.6% [4]. Breast conserving treatment, if compared with mastectomy, does not reduce survival rate even though it implies a higher incidence of ipsilateral recurrence with an annual rate of 0.5–1.0% [5,6]. Moreover, when conserving surgery is used, positive or close margins at final histology require re-excision up to 20–40% of cases. Bilateral contrast-enhanced breast MRI has been demonstrated to outperform mammography and ultrasonography in evaluating index tumor size as well as in detecting additional ipsilateral and contralateral cancers, showing otherwise undetected multifocal/multicentric disease in up to 20% of cases [7] and an incremental detection rate for contralateral cancers of about 4% [8]. In this scenario, preoperative breast MRI has been advocated for improving surgical planning by a reduction in re-excision rate, reducing in-breast cancer recurrences, and providing a screening tool for clinically unaffected contralateral breasts. While MRI has been demonstrated to prompt more extensive surgery in a not negligible proportion of women, its impact on clinical outcomes has not yet been demonstrated. Plana et al. [9] reported a 12.8% correct change (i.e., histologically confirmed) in surgical management versus a 6.3% inappropriate wider surgery (due to false positives MRI findings) while a 3% conversion to bilateral breast surgery (appropriate in 2.6%), confirming previous meta-analyses [7,8]. Thus, we would face a balanced result for the contralateral breast: about 3–4% of MRI-detected contralateral cancers versus 2–3% cumulative rate of expected contralateral cancers in the first 4–5 years. Conversely, we would have a 11–12% of MRI-induced