But translating the findings into European screening pathways will require consideration of population differences, radiation exposure and healthcare structures.
Dense breast tissue remains a challenge for breast cancer screening. While digital breast tomosynthesis (DBT) can improve lesion visualization compared with conventional mammography, cancers can still be obscured by overlapping fibroglandular tissue. At the AAPM Annual Meeting in Vancouver, researchers discussed how molecular breast imaging (MBI) could provide complementary functional information – and potentially extend its role beyond cancer detection.
MBI uses technetium-99m sestamibi and dedicated gamma cameras to visualize radiotracer uptake rather than relying primarily on anatomical differences. This can reveal areas of increased activity even when a lesion is difficult to distinguish within dense tissue on mammography or DBT.
Density MATTERS Adds Prospective Evidence
Carrie B. Hruska, PhD, from the Department of Radiology at Mayo Clinic, presented results from the Density MATTERS trial, designed to address important shortcomings in the earlier evidence for MBI. Previous studies had largely been single-center, often retrospective, and had generally compared MBI with 2D mammography rather than DBT.
The trial enrolled 2,978 participants aged 40–75 with dense breasts at five US sites. Participants underwent both DBT and supplemental MBI over two annual screening rounds, with the examinations interpreted independently.
In the first round, DBT detected five cancers per 1,000 women screened. Adding MBI increased the overall cancer detection rate to 11.8 per 1,000. For invasive cancers specifically, detection increased from 3.0 to 7.7 per 1,000.
Importantly, the effect persisted in the second screening round, when previously occult cancers discovered during initial screening would no longer inflate detection numbers. Overall cancer detection was 5.8 per 1,000 with DBT and 9.3 with DBT plus MBI; invasive cancer detection increased from 1.5 to 3.9 per 1,000.
Across both rounds, 59 women were diagnosed with breast cancer, with 29 cancers detected only by MBI. More than 70% of these incremental cancers were invasive, with a median size of 0.9 cm, and 90% were node-negative.
For Hruska, an important contribution of Density MATTERS was that it supplied the previously missing “multicenter perspective, multi-year evidence” for MBI screening.
Additional Detection Comes with Trade-offs
MBI did not detect every cancer. The trial demonstrated limitations in visualizing lesions close to the chest wall and axilla, while small lesions may also be missed. Supplemental imaging also increased recalls. In the first screening round, MBI added a further 9% recall rate to the approximately 9% associated with DBT. The additional rate fell to 5% in year two as prior MBI examinations became available for comparison.
These considerations are particularly relevant when assessing how the US findings might translate to Europe. The Density MATTERS population was predominantly white and largely at average breast cancer risk. Screening eligibility, intervals and use of DBT also vary between European countries, as do access to MRI, ultrasound and nuclear medicine services. The balance between additional cancers detected and additional recalls therefore cannot simply be assumed to be identical across healthcare systems.
Radiation exposure, infrastructure and cost-effectiveness would likewise need to be considered before MBI could be incorporated more widely into organized population screening. The trial nevertheless provides evidence relevant beyond the US: functional imaging can identify clinically significant cancers that remain occult on anatomical imaging in dense breasts.
Applications for MBI Beyond Screening
MBI may eventually have applications beyond detection. Benjamin P. Lopez, PhD, from the Department of Imaging Physics at MD Anderson Cancer Center, discussed its potential for monitoring response to neoadjuvant therapy.
Existing studies suggest MBI may have lower sensitivity but higher specificity than breast MRI for detecting residual disease. Research is also investigating whether quantitative changes in tracer uptake early during therapy could help predict pathological response.
In one 69-patient study, MBI was performed before treatment, after two therapy cycles and following completion. Changes in a quantitative SUV-MBI measure after two cycles were associated with pathological complete response or low residual cancer burden.
The evidence remains preliminary. Quantitative response criteria are not yet standardized, study populations have been small, and imaging cannot currently replace pathological assessment.
For European breast imaging, MBI therefore presents two different questions: whether stronger screening evidence can justify a place alongside established modalities for selected women with dense breasts, and whether functional measurements could eventually provide information about treatment response that anatomical imaging alone cannot.
