MRI Breast Cancer Screening for Those at High Risk

Abstract & Commentary

Synopsis: Screening techniques for the early detection of breast cancer in women at high risk commonly include clinical breast examination and conventional mammography. In the current report from a single institution, the added value of annual magnetic resonance imaging (MRI) and ultrasound were examined. Among 236 women with BRCA1 or BRCA2 gene mutations, twenty-two cancers were detected. Of these, 17 were detected by MRI, 8 by mammography, 7 by ultrasound, and only 2 by clinical breast examination (CBE). The sensitivity was 95% for all 4 modalities combined compared to 45% for mammography and CBE. The data suggest that MRI should be incorporated into the annual screening program for women at high risk for breast cancer.

Source: Warner E, et al. JAMA. 2004;292:1317-1325.

Women who carry the germline BRCA1 or BRCA2 mutations are at high risk for the development of breast cancer (estimated to be approximately 65% by age 70 for those with BRCA1 and 45% for those with BRCA2).1 Thus, increased surveillance in such women may be warranted. Current recommendations are annual mammography and semiannual clinical breast exams, but there is a question whether more intensive screening would be worthwhile.

Warner and colleagues from the Toronto-Sunnybrook Regional Cancer Center examined 236 BRCA1 or BRCA2 mutation carriers aged 25 to 65 years who underwent 1 to 3 annual screening examinations, consisting of MRI, mammography, and ultrasound, as well as clinical breast examination (CBE) every 6 months. The goal was to compare the sensitivity and specificity of these measures (mammography, ultrasound, MRI, and CBE) with the main determination to be a comparison of all 4 screening modalities together vs CBE and mammography.

Each imaging modality was read independently and scored on a 5-point Breast Imaging Reporting and Data System scale. All lesions with a score of 4 or 5 (suspicious or highly suspicious for malignancy) were biopsied. There were 22 cancers detected (16 invasive and 6 DCIS). Of these, 17 (77%) were detected by MRI vs 8 (36%) by mammography, 7 (33%) by ultrasound, and 2 (9.1%) by CBE. The sensitivity and specificity (based on biopsy rates) were 77% and 95.4% for MRI, 36% and 99.8% for mammography, 33% and 96% for ultrasound, and 9.1% and 99.3% for CBE, respectively. All 4 screening modalities combined had a sensitivity of 95% vs 45% for mammography and CBE combined.

Comment by William B. Ershler, MD

There are a number of reasons why mammography might be less effective as a screening tool for women at high risk. Included, would be technical factors that relate to the underlying breast density in younger women, the benign mammographic appearance of some BRCA-associated breast cancers and the rapid growth rate of these frequently high-grade tumors.2 The current study, like others that have recently been published, indicate the greater sensitivity of MRI for detecting cancers in this population. As reviewed in the accompanying editorial by Robson and Offit,3 a number of recently published studies, including a multi-institutional effort performed in the Netherlands4 in which 1909 women at a 15% or more life time breast cancer risk (including 358 with BRCA mutations) have demonstrated the added sensitivity of MRI. Yet, as Robson and Offit point out, it is not yet clear whether the enhanced sensitivity of MRI will translate into a reduction in breast cancer-mortality. This would require a randomized controlled trial of mammography vs MRI screening with mortality as a primary end point to establish that the more expensive technology actually translates into meaningful benefit. This trial, however would be very difficult to accrue sufficient numbers of patients. A surrogate indicator might be the stage at detection of tumor. In the currently published trials, tumor size was smaller and axillary nodes fewer in patients whose frequent in tumors detected by MRI vs. mammography. Accordingly, MRI may detect earlier stage disease and theoretically this should result in better survival.

Like so many important studies, the findings raise a litany of additional questions. Questions remain about the role of complementary screening (MRI, conventional mammography and ultrasound) as in each of the reported series, some tumors were only detected by one of these modalities. The current report and that of the Dutch group4 strongly suggest women with BRCA mutations should be offered MRI screening. However, as pointed out, the added value may depend on the imaging protocols, which have not been standardized, and the interpretive experience of the radiologists. The large number of open questions would argue against routine application of MRI screening for women not known to be at high risk. This recommendation may well change if well constructed clinical trials indicate significant advantage.

References

1. Antoniou A, et al. Am J Human Genet. 2003;72: 1117-1130.

2. Tilanus-Linthorst M, et al. Int J Cancer. 2002;102: 91-95.

3. Robson ME, Offit K. JAMA. 2004;292:1368-1370.

4. Kriege M, et al. N Engl J Med. 2004;351:497-500.

William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, D is Editor of Clinical Oncology Alert.