Petrina Causer

Prospective Study of Breast Cancer Incidence in Women With a BRCA1 or BRCA2 Mutation Under Surveillance With and Without Magnetic Resonance Imaging

PURPOSE The sensitivity of magnetic resonance imaging (MRI) for breast cancer screening exceeds that of mammography. If MRI screening reduces mortality in women with a BRCA1 or BRCA2 mutation, it is expected that the incidence of advanced-stage breast cancers should be reduced in women undergoing MRI screening compared with those undergoing conventional screening. PATIENTS AND METHODS We followed 1,275 women with a BRCA1 or BRCA2 mutation for a mean of 3.2 years. In total, 445 women were enrolled in an MRI screening trial in Toronto, Ontario, Canada, and 830 were in the comparison group. The cumulative incidences of ductal carcinoma in situ (DCIS), early-stage, and late-stage breast cancers were estimated at 6 years in the cohorts. RESULTS There were 41 cases of breast cancer in the MRI-screened cohort (9.2%) and 76 cases in the comparison group (9.2%). The cumulative incidence of DCIS or stage I breast cancer at 6 years was 13.8% (95% CI, 9.1% to 18.5%) in the MRI-screened cohort and 7.2% (95% CI, 4.5% to 9.9%) in the comparison group (P = .01). The cumulative incidence of stages II to IV breast cancers was 1.9% (95% CI, 0.2% to 3.7%) in the MRI-screened cohort and 6.6% (95% CI, 3.8% to 9.3%) in the comparison group (P = .02). The adjusted hazard ratio for the development of stages II to IV breast cancer associated with MRI screening was 0.30 (95% CI, 0.12 to 0.72; P = .008). CONCLUSION Annual surveillance with MRI is associated with a significant reduction in the incidence of advanced-stage breast cancer in BRCA1 and BRCA2 carriers.

BRCA1 mutation and young age predict fast breast cancer growth in the Dutch, United Kingdom, and Canadian magnetic resonance imaging screening trials

Purpose: Magnetic resonance imaging (MRI) screening enables early detection of breast cancers in women with an inherited predisposition. Interval cancers occurred in women with a BRCA1 mutation, possibly due to fast tumor growth. We investigated the effect of a BRCA1 or BRCA2 mutation and age on the growth rate of breast cancers, as this may influence the optimal screening frequency. Experimental Design: We reviewed the invasive cancers from the United Kingdom, Dutch, and Canadian MRI screening trials for women at hereditary risk, measuring tumor size at diagnosis and on preceding MRI and/or mammography. We could assess tumor volume doubling time (DT) in 100 cancers. Results: Tumor DT was estimated for 43 women with a BRCA1 mutation, 16 women with a BRCA2 mutation, and 41 women at high risk without an identified mutation. Growth rate slowed continuously with increasing age (P = 0.004). Growth was twice as fast in BRCA1 (P = 0.003) or BRCA2 (P = 0.03) patients as in high-risk patients of the same age. The mean DT for women with BRCA1/2 mutations diagnosed at ages ≤40, 41 to 50, and >50 years was 28, 68, and 81 days, respectively, and 83, 121, and 173 days, respectively, in the high-risk group. Pathologic tumor size decreased with increasing age (P = 0.001). Median size was 15 mm for patients ages ≤40 years compared with 9 mm in older patients (P = 0.003); tumors were largest in young women with BRCA1 mutations. Conclusion: Tumors grow quickly in women with BRCA1 mutations and in young women. Age and risk group should be taken into account in screening protocols.

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.

Differences in Natural History between Breast Cancers in BRCA1 and BRCA2 Mutation Carriers and Effects of MRI Screening-MRISC, MARIBS, and Canadian Studies Combined

Background: It is recommended that BRCA1/2 mutation carriers undergo breast cancer screening using MRI because of their very high cancer risk and the high sensitivity of MRI in detecting invasive cancers. Clinical observations suggest important differences in the natural history between breast cancers due to mutations in BRCA1 and BRCA2, potentially requiring different screening guidelines. Methods: Three studies of mutation carriers using annual MRI and mammography were analyzed. Separate natural history models for BRCA1 and BRCA2 were calibrated to the results of these studies and used to predict the impact of various screening protocols on detection characteristics and mortality. Results: BRCA1/2 mutation carriers (N = 1,275) participated in the studies and 124 cancers (99 invasive) were diagnosed. Cancers detected in BRCA2 mutation carriers were smaller [80% ductal carcinoma in situ (DCIS) or ≤10 mm vs. 49% for BRCA1, P < 0.001]. Below the age of 40, one (invasive) cancer of the 25 screen-detected cancers in BRCA1 mutation carriers was detected by mammography alone, compared with seven (three invasive) of 11 screen-detected cancers in BRCA2 (P < 0.0001). In the model, the preclinical period during which cancer is screen-detectable was 1 to 4 years for BRCA1 and 2 to 7 years for BRCA2. The model predicted breast cancer mortality reductions of 42% to 47% for mammography, 48% to 61% for MRI, and 50% to 62% for combined screening. Conclusions: Our studies suggest substantial mortality benefits in using MRI to screen BRCA1/2 mutation carriers aged 25 to 60 years but show important clinical differences in natural history. Impact: BRCA1 and BRCA2 mutation carriers may benefit from different screening protocols, for example, below the age of 40. Cancer Epidemiol Biomarkers Prev; 21(9); 1458–68. ©2012 AACR.

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.

Is mammography adequate for screening women with inherited BRCA mutations and low breast density

Background: Several observational studies have shown that magnetic resonance imaging (MRI) is significantly more sensitive than mammography for screening women over age 25 at high risk for hereditary breast cancer; however, MRI is more costly and less specific than mammography. We sought to determine the extent to which the low sensitivity of mammography is due to greater breast density. Methods: Breast density was evaluated for all patients on a high-risk screening study who were diagnosed with breast cancer between November 1997 and July 2006. Density was measured in two ways: qualitatively using the four categories characterized by the Breast Imaging Reporting and Data System and quantitatively using a computer-aided technique and classified as (a) ≤10%, (b) 11% to 25%, (c) 26% to 50%, and (d) >50% density. Comparison of sensitivity of mammography (and MRI) for each individual density category and after combining the highest two and lowest two density categories was done using Fishers exact test. Results: A total of 46 breast cancers [15 ductal carcinoma in situ (DCIS) and 31 invasive] were diagnosed in 45 women (42 with BRCA mutations). Mean age was 48.3 (range, 32-68) years. Overall, sensitivity of mammography versus MRI was 20% versus 87% for DCIS and 26% versus 90% for invasive cancer. There was a trend towards greater mammographic sensitivity for invasive cancer in women with fattier breasts compared with those with greater breast density (37-43% versus 8-12%; P = 0.1), but this trend was not seen for DCIS. Conclusion: It is necessary to add MRI to mammography for screening women with BRCA mutations even if their breast density is low. (Cancer Epidemiol Biomarkers Prev 2008;17(3):706–11)

Breast Cancers Detected with Imaging Screening in the BRCA Population: Emphasis on MR Imaging with Histopathologic Correlation

The benefit of screening with breast magnetic resonance (MR) imaging for certain patient populations at high risk for breast cancer, most notably patients with a genetic mutation in the BRCA1 or BRCA2 gene, has been established in numerous studies and is now becoming part of routine clinical practice. Despite the lower sensitivity of mammography compared with that of MR imaging, the former remains the standard of care for screening any patient population. In the BRCA1 and BRCA2 populations, the inferior sensitivity and specificity of ultrasonography (US) limit its role as a screening tool, but US remains a vital diagnostic tool because of its ability to provide guidance for biopsy of many suspicious lesions detected with MR imaging. Important features of a screening program with breast MR imaging include the following: optimization of the MR imaging technique, an awareness of the imaging features of invasive and noninvasive breast cancers detected with MR imaging, an understanding of the limitations of the various imaging modalities in both the initial screening and subsequent diagnostic work-up evaluations, and the requirement for MR imaging-guided biopsy.

Effect of the enhancement threshold on the computer-aided detection of breast cancer using MRI

RATIONALE AND OBJECTIVES To evaluate the effect that variations in the enhancement threshold have on the diagnostic accuracy of two computer-aided detection (CAD) systems for magnetic resonance based breast cancer screening. MATERIALS AND METHODS Informed consent was obtained from all patients participating in cancer screening and this study was approved by the participating institutions review board. This retrospective study was nested in a prospective, single-institution, high-risk, breast screening study involving dynamic contrast-enhanced magnetic resonance imaging. Only those screening examinations (n = 223) for which a histopathological diagnosis was available were included. Two CAD methods were performed: the signal enhancement ratio (SER) and support vector machines (SVMs). Statistical analysis was performed by tracking changes in each CAD tests diagnostic accuracy (eg, receiver-operating characteristic [ROC] curve area, maximum possible sensitivity) with changes in the enhancement threshold. RESULTS The enhancement threshold plays a significant role in affecting a CAD tests potential sensitivity, ROC curve area, and number of assumed true and false-positive predictions per cancerous examination. A high threshold can also limit the CAD-based detection of the full size of a lesion. CONCLUSIONS Enhancement thresholds can limit a CAD tests ability to diagnose a lesions full size and as such should not be raised above 60%. The clinically used SER method exhibits a high rate of false positives at low enhancement thresholds and as such the threshold should not be set lower than 50%. The SVM method yielded better results in our study than the SER method at clinically realistic enhancement thresholds.

A Vector Machine Formulation with Application to the Computer-Aided Diagnosis of Breast Cancer from DCE-MRI Screening Examinations

This study investigates the use of a proposed vector machine formulation with application to dynamic contrast-enhanced magnetic resonance imaging examinations in the context of the computer-aided diagnosis of breast cancer. This paper describes a method for generating feature measurements that characterize a lesion’s vascular heterogeneity as well as a supervised learning formulation that represents an improvement over the conventional support vector machine in this application. Spatially varying signal-intensity measures were extracted from the examinations using principal components analysis and the machine learning technique known as the support vector machine (SVM) was used to classify the results. An alternative vector machine formulation was found to improve on the results produced by the established SVM in randomized bootstrap validation trials, yielding a receiver-operating characteristic curve area of 0.82 which represents a statistically significant improvement over the SVM technique in this application.

Semi-Automatic Region-of-Interest Segmentation Based Computer-Aided Diagnosis of Mass Lesions from Dynamic Contrast-Enhanced Magnetic Resonance Imaging Based Breast Cancer Screening

Cancer screening with magnetic resonance imaging (MRI) is currently recommended for very high risk women. The high variability in the diagnostic accuracy of radiologists analyzing screening MRI examinations of the breast is due, at least in part, to the large amounts of data acquired. This has motivated substantial research towards the development of computer-aided diagnosis (CAD) systems for breast MRI which can assist in the diagnostic process by acting as a second reader of the examinations. This retrospective study was performed on 184 benign and 49 malignant lesions detected in a prospective MRI screening study of high risk women at Sunnybrook Health Sciences Centre. A method for performing semi-automatic lesion segmentation based on a supervised learning formulation was compared with the enhancement threshold based segmentation method in the context of a computer-aided diagnostic system. The results demonstrate that the proposed method can assist in providing increased separation between malignant and radiologically suspicious benign lesions. Separation between malignant and benign lesions based on margin measures improved from a receiver operating characteristic (ROC) curve area of 0.63 to 0.73 when the proposed segmentation method was compared with the enhancement threshold, representing a statistically significant improvement. Separation between malignant and benign lesions based on dynamic measures improved from a ROC curve area of 0.75 to 0.79 when the proposed segmentation method was compared to the enhancement threshold, also representing a statistically significant improvement. The proposed method has potential as a component of a computer-aided diagnostic system.