Long-term results of screening with magnetic resonance imaging in women with BRCA mutations.

BACKGROUND: The addition of breast magnetic resonance imaging (MRI) to screening mammography for women with BRCA mutations significantly increases sensitivity, but there is little data on clinical outcomes. We report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality in our screening study. METHODS: From 1997 to 2009, 496 women aged 25 to 65 years with a known BRCA1/2 mutation, of whom 380 had no previous cancer history, were enrolled in a prospective screening trial that included annual MRI and mammography. RESULTS: In 1847 screening rounds, 57 cancers were identified (53 screen-detected, 1 interval, and 3 incidental at prophylactic mastectomy), of which 37 (65%) were invasive. Sensitivity of MRI vs mammography was 86% vs 19% over the entire study period (P<0.0001), but was 74% vs 35% from 1997 to 2002 (P=0.02) and 94% vs 9% from 2003 to 2009 (P<0.0001), respectively. The relative sensitivities of MRI and mammography did not differ by mutation, age, or invasive vs non-invasive disease. Of the incident cancers, 97% were Stage 0 or 1. Of 28 previously unaffected women diagnosed with invasive cancer, 1 BRCA1 mutation carrier died following relapse of a 3 cm, node-positive breast cancer diagnosed on her first screen at age 48 (annual breast cancer mortality rate=0.5%). Three patients died of other causes. None of the 24 survivors has had a distant recurrence at a median follow-up of 8.4 years since diagnosis. CONCLUSION: Magnetic resonance imaging surveillance of women with BRCA1/2 mutations will detect the majority of breast cancers at a very early stage. The absence of distant recurrences of incident cancers to date is encouraging. However, longer follow-up is needed to confirm the safety of breast surveillance.

Optimal assessment of residual disease after neo-adjuvant therapy for locally advanced and inflammatory breast cancer--clinical examination, mammography, or magnetic resonance imaging?

PURPOSE: Accurate assessment of residual disease after neo-adjuvant chemotherapy (NEC) for women with locally advanced and inflammatory breast cancer (LABC) is critical for planning surgery. The study's purpose was to prospectively determine the optimal method (clinical examination (CE), mammogram (MG), and magnetic resonance imaging (MRI)) for assessing residual disease after NEC for women with LABC. METHODS: Women with LABC who received NEC and surgery were enrolled. Patient demographics, tumor size as measured by CE, MG, and MRI both before and after NEC, and final pathologic size of tumor were collected. Response to NEC was calculated using RECIST criteria. Paired t-tests and the Pearson correlation were used to compare tumor size on CE, MG, MRI, and final pathology. RESULTS: Forty-eight women with 50 LABC were recruited. Mean pre-NEC tumor size was 8.2, 5.1, and 6.2 cm on CE, MG, and MRI. Mean post-NEC tumor size was 2.4, 4.3, 3.9, and 3.6 cm on CE, MG, MRI, and final pathology. The Pearson correlation co-efficient between post-NEC measurements and pathology was 0.63 (CE), 0.15 (MG), and 0.49 (MRI). CONCLUSION: We found that there was limited correlation between the extent of residual disease after NEC for patients with LABC as assessed by CE, MG, and MRI as compared to final pathology.

Can breast MRI computer-aided detection (CAD) improve radiologist accuracy for lesions detected at MRI screening and recommended for biopsy in a high-risk population?

AIM: To evaluate the sensitivity and specificity of magnetic resonance imaging (MRI) computer-aided detection (CAD) for breast MRI screen-detected lesions recommended for biopsy in a high-risk population. MATERIAL AND METHODS: Fifty-six consecutive Breast Imaging Reporting and Data System (BI-RADS) 3-5 lesions with histopathological correlation [nine invasive cancers, 13 ductal carcinoma in situ (DCIS) and 34 benign] were retrospectively evaluated using a breast MRI CAD prototype (CAD-Gaea). CAD evaluation was performed separately and in consensus by two radiologists specializing in breast imaging, blinded to the histopathology. Thresholds of 50, 80, and 100% and delayed enhancement were independently assessed with CAD. Lesions were rated as malignant or benign according to threshold and delayed enhancement only and in combination. Sensitivities, specificities, and negative predictive values (NPV) were determined for CAD assessments versus pathology. Initial MRI BI-RADS interpretation without CAD versus CAD assessments were compared using paired binary diagnostic tests. RESULTS: Threshold levels for lesion enhancement were: 50% to include all malignant (and all benign) lesions; and 100% for all invasive cancer and high-grade DCIS. Combined use of threshold and enhancement patterns for CAD assessment was best (73% sensitivity, 56% specificity and 76% NPV for all cancer). Sensitivities and NPV were better for invasive cancer (100%/100%) than for all malignancies (54%/76%). Radiologists' MRI interpretation was more sensitive than CAD (p=0.05), but less specific (p=0.001) for cancer detection. CONCLUSION: The breast MRI CAD system used could not improve the radiologists' accuracy for distinguishing all malignant from benign lesions, due to the poor sensitivity for DCIS detection.

Classification of dynamic contrast-enhanced magnetic resonance breast lesions by support vector machines.

Early detection of breast cancer is one of the most important factors in determining prognosis for women with malignant tumors. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been shown to be the most sensitive modality for screening high-risk women. Computer-aided diagnosis (CAD) systems have the potential to assist radiologists in the early detection of cancer. A key component of the development of such a CAD system will be the selection of an appropriate classification function responsible for separating malignant and benign lesions. The purpose of this study is to evaluate the effects of variations in temporal feature vectors and kernel functions on the separation of malignant and benign DCE-MRI breast lesions by support vector machines (SVMs). We also propose and demonstrate a classifier visualization and evaluation technique. We show that SVMs provide an effective and flexible framework from which to base CAD techniques for breast MRI, and that the proposed classifier visualization technique has potential as a mechanism for the evaluation of classification solutions.

Adaptive bilateral breast MRI using projection reconstruction time-resolved imaging of contrast kinetics.

PURPOSE: To introduce a bilateral implementation of an adaptive imaging technique in which both dynamic and high resolution breast MR images are acquired simultaneously. MATERIALS AND METHODS: Adaptive three-dimensional bilateral breast imaging in the sagittal plane was achieved by combining two elements: a projection reconstruction time-resolved imaging of contrast kinetics (PR-TRICKS) k-space trajectory and a slab interleaved sequence that imaged alternate breasts every TR. A pilot study was performed to evaluate image quality and contrast uptake behavior, using eight patients with previously identified benign lesions. RESULTS: Adaptive reconstruction demonstrated breast lesions in all eight women with similar image quality and signal-to-noise ratio (SNR) to Cartesian images with comparable imaging parameters. Contrast enhancement curves covering the entire postinjection time period were obtained from the dynamic images and in one case compared to previous enhancement profiles from a conventional Cartesian trajectory. CONCLUSION: Bilateral dynamic and high spatial resolution images with high SNR can be achieved in a clinically feasible manner, providing both kinetic and morphologic analysis with a single data set. This may obviate the need for multiple MRI examinations for a thorough breast MRI workup.

A hybrid breast biopsy system combining ultrasound and MRI.

System design and initial phantom accuracy results for a novel biopsy system integrating both magnetic resonance (MR) and ultrasound (US) imaging modalities are presented. A phantom experiment was performed to investigate the efficacy of this hybrid guidance biopsy technique in a breast tissue mimicking phantom. A comparison between MR-guided core biopsy verses MR/US-guided core biopsy of phantom targets was realized using a scoring system based on the consistency of the acquired core samples (14 gauge). It was determined that the addition of US to guide needle placement improved the accuracy from an average score of 7.4 out of 10 (MRI guidance alone), to 9.6 (MRI/US guidance) over 21 trials. The average amount of needle tip correction resulting from the additional US information was determined to be 3.7 mm. This correction value is substantial, equal to approximately one radius of the intended targets. Hybrid US/MRI guided biopsy appears to offer a simple means to ensure accurate breast tissue sampling without the need for repeat MRI scans for verification or the need for real-time imaging in open MRI geometries.

Bone marrow transplantation in 33 patients with malignant blood diseases and severe aplastic anaemia.

Allogeneic bone marrow transplantation using HLA-identical sibling donors was performed in 29 patients with malignant blood diseases and in four patients with severe aplastic anaemia. Twenty-five patients received immunosuppressive therapy with cyclosporin A to minimize graft-versus-host disease (GVHD) and eight received methotrexate. Twenty-one of 29 patients (72%) with malignant blood diseases and three of the four patients with severe aplastic anaemia remained alive and disease-free from 0.5 to 16 (median, seven) months after transplantation. Acute GVHD, predominantly of the skin, occurred in 25 of 28 evaluable cyclosporin A recipients (of whom two died), and in all five evaluable methotrexate recipients. Mild chronic GVHD occurred in 10 of 16 evaluable patients. Interstitial pneumonitis occurred in five patients, of whom two died. HLA-identical sibling marrow transplantation is associated with a mortality similar to that of induction chemotherapy for acute leukaemia, and should be considered in adults with acute leukaemia in remission or relapse, chronic myelogenous leukaemia in metamorphosis or blastic transformation, lymphoma unresponsive to conventional therapy, and in severe aplastic anaemia.