Without data on cancer-specific mortality reduction, the decision to employ breast MRI surveillance rests heavily on other parameters, including test performance characteristics, cost, and methods of maximizing benefit vs. risk. Recent prospective studies have provided firmer data indicating that high sensitivity can be achieved with breast MRI without greatly sacrificing specificity. While reduction in cancer-specific mortality is the gold standard for surveillance tools, there is a pressing need to supplement mammography in high-risk women, particularly for
BRCA1 and
BRCA2 mutation carriers who are diagnosed with a high rate of interval tumors, roughly 50% [
45]. Breast MRI results in a lower rate of interval tumors while circumventing the limitations of surveillance for women with dense breasts. However, for whom should breast MRI surveillance be employed and what are acceptable costs?
Medium vs. high field strength MRI
Despite the promise of breast MRI, there are still some issues that must be resolved prior to its use as a standard adjunct method of breast cancer surveillance. There is not yet a standard method in place for such imaging, and no consensus on how to best interpret lesions detected by MRI, and whether or when to biopsy lesions detected by MRI alone [see ref. 31]. Additionally, the high cost of breast MRI is severely limiting. Not only is there a large cost associated with the purchase of a high field strength magnet, but also there are additional costs for housing and maintaining the unit. The use of medium field strength magnets has been criticized for their low signal-to-noise ratio (SNR) per sampling time. However, the use of a medium field strength magnet, such as a 0.5 Tesla, would come at significant cost savings of up to 1/3 that of a higher field strength MRI system. Our study provides preliminary evidence that a medium field strength breast MRI system can be effectively used for high-risk surveillance.
There is evidence that the use of a medium field strength breast MRI system is comparable to a 1.5 T system. In a study published by Kuhl
et al. [
46], MRI was performed on a midfield system without loss of sensitivity as compared to a high field system. The study looked at 42 patients imaged on both a 0.5 T and 1.5 T MRI, finding that the image quality was comparable, and, with certain compensations, the 0.5 T system was more sensitive than the larger 1.5 T MRI. In a second study, Kuhl
et al. [
47] imaged 40 patients with nodular lesions using both 0.5 T and 1.5 T field strength units to determine if the two systems were comparable in selecting benign vs. malignant lesions. Malignant lesions and fibroadenomas demonstrated a similar enhancement uptake pattern on both systems. A rapid wash-out of contrast was seen only in malignant lesions, which appeared 10 times more frequently using the 0.5 T system as compared with 1.5 T MRI.
The appearance of T1-weighted gradient echo images generated from a contrast study depends on the SNR, the contrast-to-noise ratio (CNR) and the contrast agent used. The SNR is a function of the magnetic field strength, magnet shim, flip angle, voxel size, receiver gain, RF coil and image processing parameters. Magnetic field strength directly affects the SNR and the spin relaxation properties of the tissue. The SNR is linear with field strength--everything else being equal, 1.5 T magnets produce images with three times the SNR of images from 0.5 T magnets. In addition, the T1 of a given tissue/sample type is larger at higher field strengths. This implies that at a higher field strength, the spin relaxation of a given tissue/sample may be changed more that the same tissue/sample at a lower strength and thus may increase the difference observed in pre- and post-contrast images.
The CNR is a measure of the average intensity of an object compared to the average intensity of the noise floor for a given object and pulse sequence. The CNR is a function of the relation of the pulse sequence timing parameters (e.g., TE, TR) to the spin relaxation properties (e.g., T1, T2) of the object. Because the contrast agent changes the spin relaxation properties, it changes the CNR of the image. Above a minimum SNR threshold, the ability to detect a lesion using MRI is a function of the change in CNR of pre- and post-contrast images and the voxel size acquired. If the configuration of a 1.5T MRI scanner and a 0.5T MRI scanner is such that both are above the minimum level of SNR, have comparable CNR changes after adding a contrast agent, and have identical voxel sizes and scan durations, the ability to detect lesions is similar.
Our study demonstrates that medium field strength MRI can detect tumors that have been missed by conventional screening mammography. There are, however, certainly limitations to this initial study, including its small size; up to 3 months time differential between screening mammogram and MRI; and lack of longitudinal follow up. No conclusions can be drawn regarding the overall sensitivity or specificity of screening with the 0.5 T MRI.
Screening guidelines for young high-risk women
There has been a dearth of evidence-based screening guidelines for women age < 40 with a family history of breast cancer, a
BRCA1 or
BRCA2 mutation, or other risk factors, largely because of the lack of randomized, controlled trials to inform the development of such guidelines [
48‐
50].
As evidence accumulates regarding the efficacy of bilateral prophylactic mastectomy, data regarding the efficacy of screening is of paramount importance so that women can make informed choices. In a large screening study of 251 mutation carriers, a high rate of interval tumors found on breast self-examination led to the suggestion that more frequent (i.e. semi-annual) mammography should be considered, particularly in younger women [
51]. However, among women age 40–69, the estimated cumulative risk of a false positive result after 10 mammograms is 49% [
52], resulting in additional visits, diagnostic tests, invasive procedures, morbidity, cost, and anxiety. Furthermore, there is evidence that false-positive rates are higher in younger women [
53‐
55]. Ultimately, the sequelae of screening (such as biopsies) can spur the decision to undergo prophylactic surgery, giving one pause about recommending more frequent screening.
The variations in sensitivity and specificity for breast MRI exist for several reasons, including technical factors [
56], interpretation criteria [
28,
30,
38], patient selection, concomitant use of conventional imaging, and the level of pathologic verification of the abnormalities detected. The large disparity in specificities results from a variety of technical factors. For instance, the lowest reported specificity was calculated without the use of morphologic features or quantification of enhancement, and certain high-risk lesions, such as atypical ductal hyperplasia, were considered as false positives [
24].
All high-risk MRI screening studies reported thus far have used high field-strength magnets. Stoutjesdijk
et al. [
57] found that for the indeterminate BIRADS score of 3, the sensitivity of breast MRI was 100% with a specificity of 93% (95% confidence interval = 90%–96%) and a positive predictive value of 43%. Warner
et al. [
58] reported a sensitivity of 100% and noted that all four false negative mammograms had a BIRADS score of 1. In this study, increased breast density appeared to contribute to the poor sensitivity of mammography. An update of this study reporting findings on 236 Canadian women aged 25 to 65 years with
BRCA1 or
BRCA2 mutations found a specificity of 95.4% based on biopsy of BIRADS level 4 and 5 lesions, but did not take into account the effect of breast density, nor the non-biopsy interventions engendered by level 3 lesions [
30]. High-risk women may be particularly susceptible to the emotional turmoil triggered by a diagnostic workup for breast cancer, considering their high-risk family histories.
The largest breast MRI surveillance study reported to date, based on 1909 eligible women including 358 germ-line mutation carriers, found a specificity of 89.8% for workup of level 3, 4, and 5 lesions [
29]. However, this study did not examine possible differences in test performance among women at varying levels of risk, nor was breast density taken into account. While a lower limit of 15% lifetime risk constituted study eligibility, it remains unclear whether this risk level merits high-risk surveillance, particularly in women with average mammographic breast density. Our ongoing studies of surveillance screening with medium field strength MRI have shown that the false-positive rate is three-fold lower than that of mammography [
59].