Perhaps the most exciting applications of breast MRI for the detection of breast cancer involve the screening of high-risk populations. The first attempt at using MRI to detect cancer in a mammographically and clinically normal breast was in the setting of women who present with axillary node disease [28**
]. Several studies have demonstrated that breast MRI can detect the primary cancer in women who present with malignant axillary adenopathy and unknown primary lesion. In a study reported by Orel et al
], MRI detected the primary lesion in 85% of women who presented with positive axillary nodes, and negative mammography and clinical examinations. Similar results were reported by Morris et al
The next reported application of breast MRI in a screening role was screening of the contralateral breast in women with breast cancer. The published results of several small series [30
] suggest a 5-10% cancer yield when screening the contralateral breast at the time of the original presentation. For example, Dunfee et al
] detected nine otherwise occult contralateral cancers with MRI in 92 patients. This is far in excess of the 2-3% incidence of contralateral breast cancer suggested by the National Surgical Adjuvant Breast and Bowel Project B-14 study [32
]. If these early results were confirmed in larger, more rigorous studies, then this would indicate that MRI can detect lesions before they become mammographically or clinically apparent.
There are a number of studies being performed around the world that are investigating the potential utility of breast MRI in high-risk populations. In particular, studies are being performed in the UK, The Netherlands, Germany, Canada, and in the USA. The principal investigators of these studies have been organized into a loose consortium under the umbrella of the International Working Group for Breast MRI. The Working Group Technical Report [34
] contains information on each of these studies. Patient populations vary from study to study, and the final results are not yet available. Although each of these studies is small, they will collectively accrue approximately 6000 women. Efforts are underway to develop a mechanism for collective analysis of data from across these studies. Some centers have reported interim results.
A high-risk screening study including 1500 women has been initiated in the UK, funded through the Medical Research Council and National Health Service [35**
]. Eligible patients are below the age of 50 years and either carry a known breast cancer susceptibility gene or are calculated to have at least a 50% risk of carrying such a gene. The study is being conducted at 19 centers throughout the UK. Women will undergo screening evaluations every year for 4 years that consist of both MRI and mammography. No preliminary results have been reported for the UK study.
A Canadian study is being performed at Sunnybrook and Women's College Health Sciences Center at the University of Toronto [36**
]. That pilot study is aimed at accruing 200 high-risk women. Their high-risk criteria include women who have at least three relatives who had breast cancer at age less than 50 years or ovarian cancer at any age. Women also have no previous radiotherapy for breast cancer. The protocol consists of annual mammography, ultrasound, and MRI. Clinical breast examination is performed twice each year. Preliminary results have been reported on 139 women that have been entered into the study [36**
]. To date six cancers have been detected. All six were detected by MRI. Two each were detected by clinical breast examination and mammography. Ultrasound detected three cancers. A combination of clinical breast examination and mammography would have detected four cancers. The combination of clinical breast examination, mammography, and ultrasound would also have detected four out of the six cancers. Therefore, two of the six cancers were occult to conventional screening techniques. The largest cancer detected in the study was 1.5 cm, while the smallest was 5 mm.
A study being performed by the National Expert and Training Center for Breast Cancer Screening at the University of Nijmegan in The Netherlands [37**
] is considering two populations of women: women who are at personal risk for developing breast cancer on the basis of prior biopsy results; and women in whom familial risk factors for developing breast cancer have been identified. To date, a total of 622 women have been recruited into the screening study, 228 of whom were recruited on the basis of familial risk criteria. To date, a total of 45 cancers have been reported across all individuals enroled in the study.
The National Institutes of Health in the USA is funding a multicenter pilot study that is aimed at screening high-risk women for breast cancer. The study is expected to recruit 400 women who have a 30% lifetime risk of cancer on the basis of the Gail or Clause model, or who have at least a 50% chance of carrying a breast cancer susceptibility gene as assessed using the Couch model. Women undergo screening examinations every year for 2 years that consist of clinical breast examination, mammography, and MRI. This study is currently recruiting, and no data have yet been released.
The most comprehensive report was that of Kuhl et al
]. In that study of 192 patients, of whom 105 had adequate follow up to determine disease-free status, a total of nine cancers were discovered through the use of mammography, mammography + ultrasound, and MRI screening. Three cancers were detected by mammography; mammography + ultrasound detected a total of four cancers. MRI detected all nine cancers; this included five cancers that were occult to mammography + ultrasound. These results, although very preliminary, clearly demonstrate great potential for MRI in increasing the yield of screening high-risk women.