Breast cancer screening saves lives through early detection. But for women who have dense breast tissue, standard mammograms can miss small tumors that are hidden by normal gland tissue. A new clinical study published in Radiology in September 2025 offers an important advancement for this group.

The study, titled Molecular Breast Imaging and Digital Breast Tomosynthesis for Dense Breast Screening: The Density MATTERS Trial, followed 2,978 women aged 40 to 75 years across five hospitals in the United States. All participants had dense breasts based on the American College of Radiology classification. Each woman underwent two annual screening rounds using 3D mammography, also called digital breast tomosynthesis (DBT), combined with molecular breast imaging (MBI).

What the researchers wanted to find

The goal was to measure how much the addition of MBI improved the cancer detection rate compared to 3D mammography alone. MBI works differently from a mammogram. It uses a small amount of a radioactive tracer called technetium-99m sestamibi, which highlights areas of abnormal cell activity that may represent cancer.

What they found

At the first screening round (year 1), DBT alone detected 15 cancers, equal to a rate of 5 per 1,000 women. When MBI was added, 35 cancers were found, a rate of 11.8 per 1,000. That means the addition of MBI detected 20 more cancers, an incremental cancer detection rate of 6.7 per 1,000. The number of invasive cancers found rose from 9 with DBT alone to 23 with DBT plus MBI, increasing the invasive cancer detection rate from 3.0 to 7.7 per 1,000 women.

In the second screening round (year 2), 2,590 of the original women returned for another exam. The DBT alone group again found 15 cancers (5.8 per 1,000). When combined with MBI, 24 cancers were detected (9.3 per 1,000), for an incremental detection rate of 3.5 per 1,000 women.

Overall, the researchers reported that adding MBI more than doubled the number of invasive cancers detected at both screening rounds. Most cancers detected only by MBI were small and early stage. Among the 29 women whose cancers were seen only through MBI, 21 (72 percent) had invasive tumors, 26 (90 percent) were node-negative, and the median tumor size was 0.9 centimeters. Only six (20 percent) were advanced cancers.

Safety and side effects

Out of 5,568 total combined screenings, only 10 mild side effects were recorded. These included brief lightheadedness, mild pain, or a mild rash from the injection. There were no serious adverse events reported.

Recall and biopsy rates

The first year of screening led to 534 call-backs (17.9 percent) when MBI was added, compared with 255 call-backs (8.6 percent) for 3D mammography alone. In the second year, this rate decreased to 13.8 percent with the combined method and 8.9 percent with mammography alone. The recall rate dropped by about half after radiologists became more familiar with interpreting MBI images.

The biopsy rate also rose modestly with MBI, from 2.5 percent to 5.5 percent in the first year, and from 2.3 percent to 4.1 percent in the second year. However, the positive predictive value of these biopsies remained similar to mammography alone, meaning the accuracy of the findings was consistent.

What this means to women

Dense breast tissue is common and is found in nearly half of all women. It not only hides tumors on mammograms but is also associated with a slightly higher risk of developing breast cancer. The study’s authors noted that traditional screening can miss more than half of invasive cancers in women with dense breasts.

By adding molecular breast imaging, doctors can detect cancers that are often invisible on mammography. Most of these are early and treatable. The authors concluded that MBI increases invasive cancer detection by more than 2.5 times and only modestly increases follow-up testing.

They also emphasized that MBI is relatively accessible compared to MRI, with a lower cost and shorter scan time, and it may be a good supplemental screening option for women who cannot undergo MRI or contrast-based tests.

In simple terms

For women with dense breasts, combining molecular breast imaging with standard 3D mammography means better chances of finding cancer early. The study shows that this approach can uncover hidden tumors before they grow or spread, providing another step forward in saving lives through early detection.

Source:
Hruska CB, Hunt KN, Larson NB, Miller PA, Ellis RL, Shermis RB, Rauch GM, Conners AL, Spilde JG, Semaan DT, et al. Molecular Breast Imaging and Digital Breast Tomosynthesis for Dense Breast Screening: The Density MATTERS Trial.  Radiology. 2025;316(3):e243953.