Breast Density Should Play a Greater Role in MRI Screening Guidelines

Guidelines for breast cancer screening with MRI were first proposed in 2007, only a few years after its clinical introduction. Those initial guidelines, which were generated by a committee sponsored by the American Cancer Society (ACS), have served as the template for similar recommendations by several organizations, with a singular goal regarding patient candidacy for MRI screening, a qualifying threshold based on risk stratification. Higher risk in those patients recommended for MRI screening translates to higher cancer detection rates, which in turn impacts cost-effectiveness. But there is another variable that should be as important as risk stratification in selecting patients for MRI screening: the probability that screening mammography will fail to detect developing cancer. That failure rate is a function of breast density, included in the MRI screening guidelines as a traditional risk factor but neglected when one considers its role as the primary cause of false-negative mammograms. The two implications of dense mammograms are essentially independent: (1) refining risk stratification and (2) predicting the "miss rate" of mammography. In the 2007 guidelines, indications for annual screening MRI, in addition to mammography, were based on patients having a calculated probability of "greater than 20-25% lifetime risk" for developing breast cancer. Other categorical risks, such as BRCA positivity, are listed in the ACS guidelines, but in effect, the threshold for adding MRI to the screening regimen has been a 20% lifetime risk for the development of breast cancer. While risk stratification in the original MRI screening guidelines had a number of inconsistencies, the focus herein is the questionable placement of high-density patients into the category described as "no policy for or against MRI, more research needed," a category where lifetime risks were grouped as 15-19%. Thus, mammographic density was relegated to its role as a traditional risk factor, while its potentially more significant impact, predicting the "miss rate" of mammography, had no role in patient selection for screening MRI. The 2007 ACS guideline committee was limited by the lack of available data, and since there was no evidence for mortality reduction at the time, the decision was made to follow the patient selection criteria that had been used in the six international MRI screening trials, even though there was little consistency among those trials. Since then, the number of screening MRI trials has more than doubled, and new trials are being designed and implemented with a focus on both features of density: risk and cancer camouflage. Enough evidence has accumulated during the 16 years subsequent to the original ACS high-risk screening guidelines to consider a complete revision that accounts for both numerical risk levels and density levels, much like what was used in the ACRIN 6666 trial. In establishing a new set of guidelines, our first question should be: What is the "miss rate" of mammography in this patient? If the chance of a false-negative mammogram is as high as we see with Level D density, then the decision to include MRI becomes straightforward. The traditional risk assessment would then be used to help determine the optimal interval between MRI screens while maintaining cost-effective cancer detection rates.