Recent trends in the utilization of molecular breast imaging in the United States.

1.
Introduction
The American Cancer Society (ACS) estimates that in 2025, approximately 316,950 women will be diagnosed with invasive breast cancer, and more than 42,170 women will die from the disease.1 The American College of Radiology (ACR), the ACS, the United States Preventive Services Task Force (USPSTF), and the National Comprehensive Cancer Network (NCCN) all recognize that early detection decreases breast cancer mortality. While mammography is the most widely used method for the early detection of breast cancer and the only modality proven to reduce mortality, its sensitivity in dense breasts and high-risk women is limited.2–4 To overcome the limited sensitivity of mammography, the ACS, ACR, and NCCN all recommend annual supplemental breast cancer screening in high-risk patients and in those with dense breasts but otherwise average risk.4 Magnetic resonance imaging (MRI) is currently the preferred method for supplemental screening, given its high diagnostic accuracy. However, its use is restricted by high costs, limited accessibility,5 as well as multiple contraindications including claustrophobia, renal disease, MR-incompatible implantable devices, and body habitus.6
As one of the alternative supplemental screening modalities for patients meeting criteria but unable to undergo breast MRI acknowledged by the updated ACR Appropriateness Criteria, molecular breast imaging (MBI) demonstrates excellent diagnostic performance. Six large studies, including over 6000 patients after 2011 showed an incremental cancer detection rate from 7.5 to 16.5 per 1000 exams when screening MBI is used as supplemental screening with DBT.7 MBI was shown to have similar sensitivity (84% versus 89%) and specificity (82% versus 81%) compared with MRI for supplemental screening.8,9 MBI may also be used for initial staging of newly diagnosed breast cancer. For example, MBI has been shown to detect additional disease in up to 10.9% of patients and changed surgical management in 11.9–18.3% of patients in a retrospective study.10 One meta-analysis showed that MBI was 86% sensitive and 69% specific in evaluating residual disease, similar to MRI (83–87% sensitive and 54–83% specific); demonstrating that MBI can be used for monitoring neoadjuvant therapy. Finally, MBI can also be employed for diagnostic work-up of suspicious symptoms with a negative mammogram and ultrasound, addressing indeterminate mammographic or ultrasound results, or managing discordant biopsy results.11
Despite the strong performance of MBI in both screening and diagnostic settings, in addition to its feasibility, safety, affordability, and capability for biopsy that has been well-demonstrated in multiple studies, there is limited usage of this technique.12,13 To our knowledge, the utilization of MBI across the U.S. population has not been studied.

2.
Methods
This retrospective claim analysis used data from the Merative MarketScan Commercial Database from January 1, 2017, to December 31, 2022. The Commercial Database contains deidentified medical claims from over 150 million employees, spouses, and dependents less than 65 years of age from employer-sponsored health plans in all 50 states and U. S. territories. This database includes a variety of fee-for-service, preferred provider organizations, and capitated health plans. The MarketScan Database consists of all medical claims with billing codes based on the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), and Current Procedural Terminology (CPT) codes. The Institutional Review Board considered this study exempt because the MarketScan Database is a limited data set with de-identified health information. The inclusion criteria included women aged 25–64 years with continuous enrollment in a participating health plan for at least three months from January 1, 2017, through December 31, 2022. Data from September 1, 2016, through December 31, 2016, was used to establish that participants in early 2017 met these inclusion criteria. The 3-month enrollment period was included to increase data stability and reduce confounding variables, enabling isolation of the true underlying frequency of imaging. To avoid underestimating utilization in women with concurrent Medicare insurance coverage, the age limit was capped at 64 years. MBI utilization was captured from the outpatient services file using CPT or Healthcare Common Procedure Coding System (HCPC) codes for MBI, 78800, 78801 (radiopharmaceutical localization of tumor or distribution of radiopharmaceutical agent[s]; limited area), and S8080 (Scintimammography) (Fig. 1). Each patient was assigned to a region based on residence when the MBI was performed to explore regional differences in utilization.
2.1.
Data analysis
Results are reported in person-years of observation (PYO). This measurement considers the number of people in the study and each person’s observation time based on continuous health insurance enrollment. This is necessary to adjust for participants changing insurance enrollment status throughout the study period. The PYO rate reflects the number of MBI studies performed per 1000 PYO. Temporal trends were analyzed using generalized linear models with reported P-values representing the effect of the year. All data programming and statistical analyses were performed in SAS version 9.4 (SAS, Cary, NC).

3.
Results
During the 6-year study, 3024 study-eligible women underwent 3648 MBI scans. For comparison, 7,694,641 study-eligible women underwent 16,317,862 mammograms. Study-eligible women undergoing breast MBI ranged in age from 26 to 64 years, with a median of 51 years (Fig. 2). The median duration of health insurance enrollment for women who underwent MBI was 89.5 months (range 6–204 months), and the mean was 98.1 months (SD 60.8).
The median duration of enrollment of the total eligible study population was 21 months (range 3–72 months), and the mean was 27.4 months (SD 21.5 months). From 2017 to 2022, breast MBI utilization decreased by 31%, from 7.9 to 5.6 per 1000 PYO (P < 0.0001). The overall trend in utilization was primarily stable from 2017 to 2021, with a sudden decrease in 2022 from 8.3 to 5.6, a 33% reduction. The lowest utilization rate was 5.6 per 1000 PYO in 2022 (Fig. 3).
When subdivided by age group (Fig. 4), all ages demonstrated decreased MBI utilization over the study period. The youngest age groups, 25–29 and 30–34, declined to zero utilization by the year 2022. Women aged 45–49 had the highest utilization rate at 15.1 per 1000 PYO (P < 0.0001) in 2019.
The lowest performance rate of MBI over the study period was in the 25–29-year-old age group at 0.15 per 1000 PYO, the 30–34-year-old age group at 0.23 per 1000 PYO, and the 35–40-year-old age group at 2.20 per 1000 PYO, which is expected as routine imaging is not typically performed until the age of 40. The 60–64 age group had the overall highest MBI utilization of 12.3 per 1000 PYO over the study period (Fig. 5). Approximately 22% (665/3024) of all MBIs were performed in the 45–49-year-old age range.
To determine the frequency with which women underwent MBI, women with sufficient continuous enrollment to have the opportunity for a subsequent MBI were examined.
Of 3024 study-eligible women with >13 months continuous enrollment, 83% (2522/3024) underwent only one MBI (Table 1). Of the 1646 women with >18 months of health insurance enrollment after the first MBI, 28% (453/1646) had a second MBI during that time. Of the 899 women with >36 months of health insurance enrollment after the first MBI scan, 36% (320/899) had a second MBI scan, and 9% (82/899) received a third MBI scan during that period.
Utilization and utilization trend varied by geographic location, rising from 2.10 to 4.08 (+89%, P = 0.006) in the western U.S during the study period. Similarly, utilization increased from 2.61 to 2.82 (+5%, P = 0.60) per 1000 PYO in the southern U.S. Conversely, In the northeast, utilization declined from 3.12 to 1.11 (−66%, P = 0.001). Downward pattern was also observed in the north-central region, where utilization decreased from 29.84 to 17.39 (−43%, P < 0.0001).

4.
Discussion
Our study demonstrated that the utilization of MBI is persistently low over the 6-year period from 2017 to 2022. This aligns with the literature review results and prevailing perception. While there is no prior study dedicated to examining the real-world utilization statistics of MBI, only four U.S studies conducted after 2016 with fewer than 4000 participants reported contemporary use of MBI.14–16 Patient education/advocacy sources such as DenseBreast-Info.org and komen.org similarly describe MBI as not widely available in the United States.
The main reason for limited use of MBI, especially as a preferred supplemental screening method, is concern over the whole-body radiation dose.9 As Table 2 demonstrates, MBI is associated with the highest whole-body radiation exposure of all breast imaging modalities despite advances in dose-reduction. The estimated effective radiation dose for the whole body (2.1 mSv with 8 mCi Sestamibi) is now well below the average annual natural background level in the U.S. (6.2 mSv).17,18 However, ACR usually considers tests with effective dose <1 mSv to be very low risk and appropriate for screening.
The other barrier to MBI adoption is lack of physical availability. According to the U.S. site directory of facilities performing MBI maintained by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), MBI is only available in 32 centers within 19 states, mostly select academic and high-volume breast centers.19 The increased frequency of MBI use in the North Central Region shown in our study likely reflects the presence of large medical institutions, such as the Mayo Clinic in Rochester, a recognized leader in MBI use. To offer MBI, institutions must provide a dedicated MBI imaging system. In contrast, most other supplemental breast imaging can be implemented using existing infrastructure: breast MRI on standard MRI machines with breast coils, contrast-enhanced mammography with upgrade of the conventional mammographic unit and IV capability, and breast ultrasound, widely available in breast centers. Furthermore, institutions must incorporate a nuclear medicine wet lab for safe preparation and handling radiopharmaceuticals, a licensed technologist to administer Tc-99 m sestamibi, and coordination between the breast section and the nuclear medicine section.
Intrinsic characteristics of MBI, such as relatively long acquisition time (28–40 min) may also reduce its appeal and limit its use.
Finally, the established availability and excellent diagnostic performance of competing supplemental screening imaging modalities including MRI and CEM also restrict the community diffusion of MBI. As a result, few large-scale clinical trials of MBI are currently underway. This in turn leads to a gap of evidence such as absence of incidence-round screening data which hinders broader guideline endorsement and recommendation of MBI.
Nevertheless, there is a large unmet need for supplemental screening and diagnostic breast imaging2 Statistics show that approximately 9–21% of women are high-risk, defined as women with higher than 20% lifetime risk of developing breast cancer.20 Moreover, 43% of the 40 million screening population in the US have dense breast tissue, translating to roughly 17 million individuals eligible for annual supplemental screening.21 In September of 2024, federal dense breast notification legislation was implemented, and the Food and Drug Administration now requires reporting of breast density following mammography.5 While MRI has the best overall diagnostic performance,22 15% of the patients eligible for MRI cannot undergo the study or cannot afford the cost.5 A recent retrospective claims analysis demonstrated that the utilization of breast MRI from 2007 to 2017 among women aged 25–64 years was consistently less than 1% of the study’s eligible population.23 Compared to MRI, MBI has reasonable sensitivity, specificity, lower cost, and fewer contraindications, making it a promising alternative supplemental screening tool.24
Given the aging population of the U.S. and recent federal regulations on dense breast notification, there is an increased need for accessible, safe, and cost-effective supplemental screening and diagnostic imaging options that perform well in high-risk patients and patients with dense breasts. MBI demonstrates high sensitivity, is cost-effective, and has fewer contraindications than MRI.10 However, concerns for increased radiation dose and inaccessibility, especially in the western U.S., have contributed to underutilization of MBI.
Emerging technologies such as abbreviated breast MRI and CEM provide high diagnostic accuracy with few downsides. Studies show sensitivity of CEM up to 91% with a radiation dose much closer to that of DBT, providing an accessible cost-effective alternative for breast cancer screening in high-risk individuals or in those with an allergy to Gadolinium.25 Larger studies are needed to evaluation CEM’s role in screening, such as the ongoing Contrast Enhanced Mammography Imaging Screening Trial (CMIST) which aims to determine whether CEM improves breast cancer detection and reduces false positive exams in women with dense breasts, compared to DBT. Additionally, a CEM-guided biopsy system is now commercially available, streamlining the work-up of CEM-detected suspicious lesions.26 The wide availability of CEM capable units and ease of implementation have the potential to absorb the demand for supplemental imaging in the future.
4.1.
Limitations
The study is limited to the population included in the MarketScan insurance database, which may not fully represent the U.S. population. We excluded Medicare-aged women over the age of 65, which represents approximately 20% of the U.S. population and 50% of breast cancer patients in the U.S..27 The database does not include MBI performed outside of insurance policies, including those who transitioned out of the private health insurance programs included in the database. Additionally, due to the small number of women receiving MBI in the MarketScan Database, it may be difficult to extrapolate trends in utilization. Furthermore, the study period overlapped with the COVID-19 pandemic, which resulted in decreased utilization for many screening exams. The authors could not distinguish between screening and diagnostic MBI scans, as ICD diagnostic codes are used for billing purposes and may not reliably distinguish the clinical indication for an MBI exam. Finally, the MarketScan Database provides user-limited data to protect the identity of patients; therefore, precise location data for where the study was performed cannot be reported.

5.
Conclusion
MBI is an accurate, affordable, and safe option for patients unable to undergo supplemental screening with MRI. With the recent advances of MBI-guided biopsy capability and radiation dose reductions, MBI is an alternative screening method that can be used for supplemental screening. However, challenges such as concern over whole body radiation exposure and limited availability contribute to overall low utilization of MBI in the United States.