Supplemental Molecular Breast Imaging Enhances Cancer Detection in Women with Dense Breasts

A new multicenter study published in Radiology, the journal of the Radiological Society of North America (RSNA), finds that combining molecular breast imaging (MBI) with digital breast tomosynthesis (DBT) significantly improves the detection of invasive breast cancers in women with dense breast tissue. While the combination modestly increases recall rates, the boost in early detection may offer vital benefits, particularly in uncovering clinically significant cancers that DBT alone may miss.

"To our knowledge, this is the first multicenter, prospective evaluation of MBI as a supplement to DBT in women with dense breasts," said lead author Carrie B. Hruska, Ph.D., professor of medical physics at Mayo Clinic in Rochester, Minnesota.

Approximately 47% of women screened for breast cancer have dense breast tissue, a factor known to reduce the effectiveness of traditional mammography and DBT—an advanced 3D mammographic technique. DBT improves detection compared to 2D mammography, but limitations remain, especially for dense tissue where cancers may be masked.

MBI, which uses a radiotracer to highlight metabolic activity in breast tissue, is one of several supplemental screening options. Others include breast ultrasound, MRI, and contrast-enhanced mammography. The Density MATTERS Trial(Molecular Breast Imaging and Tomosynthesis to Eliminate the Reservoir) was designed to evaluate MBI’s potential as a complementary tool to DBT.

The prospective study enrolled 2,978 asymptomatic women between ages 40 and 75 with visually confirmed dense breasts, spanning five sites across the U.S. from 2017 to 2022. Participants underwent two annual screening rounds: a baseline (prevalence) screen and a follow-up (incidence) screen one year later. Final follow-up was completed in September 2024.

Participants had a mean age of 56.8 years, and the majority were postmenopausal with category C breast density. Notably, 80% had no family history and 98% had no personal history of breast cancer, making them representative of a general screening population.

Across both rounds, MBI alone detected 30 cancerous lesions in 29 participants that DBT missed. Of these lesions, 22 (71%) were invasive, with a median size of just 0.9 cm. Furthermore, 90% of the cancers detected by MBI were node-negative, while 20% were node-positive, indicating MBI’s ability to catch both early and clinically significant cancers.

“MBI detected an additional 6.7 cancers per 1,000 screenings at Year 1 and an additional 3.5 cancers per 1,000 screenings at Year 2,” Dr. Hruska noted. “Among the incremental cancers detected only by MBI, 70% were found to be invasive.”

In Year 1, DBT alone detected 4 of 7 node-positive cancers (57%), while the combination of DBT and MBI detected all 7. In Year 2, DBT alone detected just 1 of 6 node-positive cases (16%), compared to 4 of 6 (67%) with combined screening. Two node-positive cancers went undetected by either method.

“Someone who's having their routine annual screen every year should not be diagnosed with advanced breast cancer,” Dr. Hruska emphasized. “That's just unacceptable. With a supplemental screening every few years, we hope to find cancers earlier and see the diagnosis of advanced cancer go way down.”

The study’s strength lies in its diverse mix of participants and institutions, including Mayo Clinic, MD Anderson Cancer Center, Henry Ford Health System, and regional clinics like ProMedica Breast Care. With 12% of the cohort comprising minority patients, the findings carry broader applicability.

Dr. Hruska encourages women to continue regular mammography but also to understand DBT's limitations. “I don’t want to discourage anyone from getting a mammogram, because they absolutely should,” she said. “However, DBT doesn’t find all cancers, and women need to understand its limitations and consider how supplemental screening can fill the gap.”

MBI, she added, is a safe, well-tolerated, and relatively affordable option. “MBI uses a well-established radiotracer that’s been used in cardiac imaging for a really long time,” Dr. Hruska explained. “It has fewer risks than other modalities and no contrast reactions.”

Ultimately, informed choice and personalized care remain central. “If a woman has a choice of modalities, it’s important that she understands the benefits and risks of each and be involved in the decision-making,” Dr. Hruska said.