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.

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.

Stromal fibrosis of the breast.

OBJECTIVE: The purpose of this retrospective study was to describe the imaging features of stromal fibrosis of the breast and to determine the false-negative rate (number of cancers missed) at percutaneous biopsy. MATERIALS AND METHODS: Between January 1997 and October 1999, 1095 imaging-guided core biopsies were performed. Patients were included in our study if stromal fibrosis was the predominant histologic finding. Cores adjacent to previous excisional biopsies or from calcified lesions were excluded. RESULTS: Stromal fibrosis was diagnosed in 74 (6.8%) of 1095 imaging-guided core needle biopsies in 73 patients. The 10 mammographic lesions were variable in appearance. Most of the sonographic lesions were indeterminate, with 16 (25%) of 64 showing suspicious features. Discordant imaging resulted in three patients having a second core biopsy and nine patients having an excisional biopsy. The two false-negative findings were the result of an infiltrating lobular carcinoma and an infiltrating ductal carcinoma, the latter diagnosis delayed for 6 months. CONCLUSION: The low incidence (2.7%) of missed cancers in our series suggests that patients diagnosed at core biopsy as having stromal fibrosis can be treated conservatively with a short-term follow-up protocol. However, it would be prudent to continue to recommend either a second core biopsy or an excisional biopsy for imaging features that cannot be reliably differentiated from malignancy.

Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer.

PURPOSE: Recommended surveillance for BRCA1 and BRCA2 mutation carriers includes regular mammography and clinical breast examination, although the effectiveness of these screening techniques in mutation carriers has not been established. The purpose of the present study was to compare breast magnetic resonance imaging (MRI) with ultrasound, mammography, and physical examination in women at high risk for hereditary breast cancer. PATIENTS AND METHODS: A total of 196 women, aged 26 to 59 years, with proven BRCA1 or BRCA2 mutations or strong family histories of breast or ovarian cancer underwent mammography, ultrasound, MRI, and clinical breast examination on a single day. A biopsy was performed when any of the four investigations was judged to be suspicious for malignancy. RESULTS: Six invasive breast cancers and one noninvasive breast cancer were detected among the 196 high-risk women. Five of the invasive cancers occurred in mutation carriers, and the sixth occurred in a woman with a previous history of breast cancer. The prevalence of invasive or noninvasive breast cancer in the 96 mutation carriers was 6.2%. All six invasive cancers were detected by MRI, all were 1.0 cm or less in diameter, and all were node-negative. In contrast, only three invasive cancers were detected by ultrasound, two by mammography, and two by physical examination. The addition of MRI to the more commonly available triad of mammography, ultrasound, and breast examination identified two additional invasive breast cancers that would otherwise have been missed. CONCLUSION: Breast MRI may be superior to mammography and ultrasound for the screening of women at high risk for hereditary breast cancer.

Analysis of mammographic density and breast cancer risk from digitized mammograms.

To evaluate the association between mammographic density and breast cancer risk, a simple, observer-assisted technique called interactive thresholding was developed that allows reliable quantitative assessment of mammographic density with use of a computer workstation. Use of this technique helps confirm that mammographic density is one of the strongest risk factors for breast cancer and is present in a large proportion of breast cancer cases. The strong relationship between mammographic density and breast cancer risk suggests that the causes of breast cancer may be better understood by identifying the factors associated with mammographically dense tissue and determining how such tissue changes as these factors vary. Furthermore, because it can be modified, mammographic density may also be a good vehicle for the development and monitoring of potential preventive strategies. Areas of ongoing investigation include evaluating a potential genetic component of mammographic density by comparing density measurements in twins and understanding changes in density relative to age, menopausal status, exogenous hormone use, and exposure to environmental carcinogens. In addition, work is ongoing to establish measurements from imaging modalities other than mammography and to relate these measurements directly to breast cancer risk.

Magnetic resonance imaging in potential postsurgical recurrence of breast cancer: pitfalls and limitations.

OBJECTIVE: To determine the sensitivity and specificity of magnetic resonance imaging (MRI) of the breast for detecting recurrent carcinoma. PATIENTS AND METHODS: Thirteen patients ranging in age from 47 to 77 years who had undergone lumpectomy 5 months to 8 years earlier and who had mammographic findings suggestive of recurrence underwent contrast-enhanced dynamic MRI. Histologic confirmation was obtained in all cases. RESULTS: Of the eight lesions (in seven patients) for which biopsy proved recurrence, MRI correctly identified six; there were two false negative results. Of the six benign lesions, four were correctly identified by MRI. The two false positive results involved fat necrosis and a foreign-body reaction respectively. CONCLUSION: These results confirm previous reports of the poor specificity of MRI of focal breast lesions. The authors therefore recommend caution in the use of breast MRI in the assessment and management of suspected recurrent carcinoma.

Role of equalisation mammography of dense breasts.

Parenchymal patterns characteristic of dense breasts are known to degrade the mammographic detection of small breast cancers and microcalcifications. This arises from large variations in exposure of the film, resulting in reduced image contrast over areas of suboptimal exposure. Based on sensitometric measurements of mammograms from a typical patient population, it is shown that over 60% of a typical mammogram in Wolfe's DY classification was found to be exposed suboptimally, suggesting a significant margin for improving mammography for these patients. In order to address this problem, a prototype mammographic version of scanning equalisation radiography (MSER) has been developed, which delivers a patient-specific spatially non-uniform distribution of breast exposure, adjusted to maintain optimal film exposure and contrast over the entire mammogram. Anthropomorphic phantom MSER images show a marked improvement in subjective image quality relative to conventional mammograms, while exhibiting a similar radiation risk. The detection of small microcalcifications and fibrils over clinically significant breast densities is found to be improved by factors eight and four, respectively. Such a system may be clinically practical through the use of multiple-beam equalisation methods with available X-ray tube technology.