Our prospective multimodality screening study of 609 high-risk patients consisting of FSM, DM, MRI, and WBUS resulted in detection of 20 cancers in 18 patients. The unique blinded, unblinded, and consensus reading paradigm simulated the clinical process of screening followed by diagnosis and thus provides strong insight into modality performance in clinical context. Although at the time of enrollment the patients in our study had no unresolved suspicious findings on clinical breast examination and had a negative or resolved screening mammogram within 6 months of study entry, reinterpretation of the FSM resulted in upgrading findings in three participants and findings not called on the outside study in three participants that ultimately led to a diagnosis of cancer. The modest reproducibility of mammography interpretations is well known.6,7
Although compliance with biopsy recommendations was based on the discretion of the primary care clinician, most patients with final consensus assessments of 4 or higher underwent biopsy. The relatively large number of MRI lesions that seem to not have undergone biopsy are primary related to nonvisualization at the time of the biopsy scan. All of these patients were cancer free at 2 years of follow-up.
Our results confirm findings suggested in other previously published screening studies on high-risk populations.8–18
The sensitivity of MRI was higher than that for mammography; however, this was not statistically significant in part because of the limited power to detect all but huge differences in sensitivity with modest numbers of cancers detected. However, even with our modest numbers of detected cancers, the sensitivity of MRI was significantly better than sonography (P
= .002). The specificity for MRI was somewhat lower than for the other modalities, but this difference was in part mitigated by a reduction in the number of biopsies related to resolution of the finding at the time of the biopsy scan. This supports the value of the biopsy scan as a short-term follow-up assessment.
Our data support the recommendations made by the American Cancer Society for MRI screening of women with greater than 20% to 25% lifetime risk for breast cancer.19
Note that the overall cancer yield of FSM is underestimated in our study because women presented with nonactionable FSM. The FSM yield is reflective of rereading of the FSM. In addition, DM and FSM are expected to correlate, so that the overall DM yield would be higher than that which is estimated from this study if it were used in isolation. Therefore, our study reflects the incremental yield over a baseline FSM examination interpreted by a community radiologist.
On the basis of our results, the role of screening ultrasound is unclear. Although, the WBUS studies were performed by dedicated breast imagers in a university hospital, there was one cancer detected by ultrasound alone. Ultrasound had the lowest sensitivity and biopsy yield. Although American College of Radiology Imaging Network (ACRIN) 6666 clearly showed mammographically occult ultrasound-detected cancers, the positive predictive value was 8.9%.4
In addition, the ACRIN trial did not have the benefit of MRI in the first round of screening. In addition, if screening WBUS studies are performed by radiologists, taking into consideration the time spent by the radiologist performing and interpreting the study, the cost of the ultrasound examination may be higher than for a contrast-enhanced MRI study.
The Digital Mammographic Imaging Screening Trial (DMIST), which compared the sensitivity of FSM with that of DM, found that DM was more sensitive in cancer detection in pre- or perimenopausal women, women with dense or extremely dense breasts, and women less than 50 years old.3
In our group of women with screening-detected cancers, 39% of the women (seven of 18 women) had scattered fibroglandular density, and the remaining 61% (11 of 18 women) had dense breast tissue. Of the 20 individual cancers detected in our study, DM detected seven cancers, and FSM detected six cancers (). These results would be consistent with the DMIST findings; however, the increased cancer yield falls well below the yield provided by MRI. With the rapid growth in the number of centers offering DM, high-risk patients might be best served by having their mammogram performed using a digital system.
At this time, there are no randomized studies demonstrating that MRI improves survival by earlier detection; such a study would be expensive to undertake and would take years to complete if mortality was the end point. The study also would need to enroll a large number of patients to achieve statistical significance. The various screening MRI trials8–18
have consistently showed high sensitivity of MRI in the detection of occult breast cancer. It is also noted that MRI was particularly effective in detecting invasive cancer, detecting cancer in nine of 10 patients with invasive cancer who were imaged with MRI and being the only modality to detect five invasive cancers.
In conclusion, our results, as well as the results of previously reported studies, support the use of MRI as a complement to mammography in high-risk populations. DM does not seem to be an alternative to MRI in this regard but may represent an alternative to FSM in these patients. The role of sonography in this population seems limited to patients with a contraindication to MRI.