Large-scale TMIST breast cancer screening trial achieves enrollment goal, paving the way for data that provides a precision approach to screening

The Tomosynthesis Mammographic Imaging Screening Trial (TMIST) has reached its enrollment goal of 108,508 women, as announced today by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN). The study, funded by the National Cancer Institute (NCI), one of the National Institutes of Health, will now proceed with the completion of regularly scheduled mammograms and follow-up on all participants through 2027. Key in this follow-up is the collection of biospecimens and data that will help researchers learn how to personalize breast cancer screening for women.

Participants in TMIST were randomly assigned to receive either 2-D (standard) or 3-D mammograms. TMIST is the first randomized controlled trial aimed at identifying women for whom digital breast tomosynthesis (DBT or 3-D mammography) may be more effective than two-dimensional (2-D) digital mammography in reducing the risk of advanced breast cancer. The 3-D mammography technique takes multiple images of the breast from different angles to create a three-dimensional image.

Despite being in use for the last decade, there has not been clinical evidence that 3-D outperforms traditional 2-D mammograms in detecting aggressive breast cancers. Both methods involve compression of the breast along with radiation exposure. The ability of these different technologies to detect advanced cancers is being compared; while 3-D mammography has been seen to find more cancer, it is unknown if these additional cancers found are ones that are advanced and more likely to cause death. Primary TMIST results may be published as early as 2028.

"Strong recruitment rapidly increased enrollment despite a worldwide pandemic that has kept breast cancer screening rates below pre-COVID-19 levels,” said TMIST Study Chair Etta D. Pisano, MD, FACR (pictured at left). “We are proud of these recruitment efforts and diverse study population, which includes participants in the United States, Argentina, Canada, and other countries. “We are excited to continue gathering and analyzing images, biospecimens, and data as we power toward the publication of TMIST results.”

TMIST is also creating significant future opportunities by developing the world's largest curated dataset of breast cancer screening images, clinical data, and biospecimens. This comprehensive dataset will be available to researchers, enabling them to discover new screening strategies and tools. These advancements may help physicians to provide personalized recommendations for each woman, taking into account her risk factors, individual circumstances, and genetics.

"The primary TMIST study question is whether tomosynthesis or 3-D mammography is more sensitive for those breast cancers that are more likely to lead to a woman's death from breast cancer," said Dr. Pisano. "Although prior studies suggest that tomosynthesis screening finds more cancers than 2-D, we do not know if it leads to more lives saved. Does it lead to a reduction in aggressive cancers because they are found earlier, such as triple-negative breast cancer, for example? If TMIST finds a reduction in aggressive cancers, it would suggest tomosynthesis is saving more lives than the older technology."

TMIST data will also assist doctors in improving the process of identifying women at high risk for developing cancer, as well as in optimizing the use of both mammographic technologies in the future.

A major strength of the TMIST cohort is its diversity and representation of women from around the globe. Worldwide, 48% of TMIST participants are Hispanic or Latino. To support the recruitment of diverse populations, promotion and education resources were published in multiple languages, which facilitated the involvement of hospitals, cancer centers, and clinics (sites) that serve diverse communities. Furthermore, ECOG-ACRIN collaborated with the American College of Radiology® (ACR®) to enhance recruitment efforts. As a result, TMIST has become one of the most racially diverse populations of any NCI trial.

In the United States, fewer than half of all accredited mammography scanners are 3-D units, and 10% of imaging facilities in the US do not have any 3-D scanners. Many of these facilities are in medically under-served geographic areas. Further, a study published in the Journal of the American College of Radiology (JACR®) showed that Black women are far less likely to be screened with 3-D than white or Asian women.

“We are encouraged by the diversity of patients in TMIST. Considering the high breast cancer mortality rates among individuals in under-served populations, TMIST’s diverse patient group carries the potential to help us better understand the disease’s predictive factors, improve early detection for as many women as possible, and lead to better, more individualized screening strategies,” said ECOG-ACRIN Health Equity Committee Chair Melissa A Simon, MD, MPH (pictured at left ).

ECOG-ACRIN leads TMIST (NCT03233191) with support from the National Cancer Institute. TMIST is being conducted at 133 study sites worldwide. Countries include Argentina, Canada, Chile, Peru, Italy, South Korea, Spain, Taiwan, Thailand, and the United States. Many TMIST sites in the US are outside of major cities through the NCI Community Oncology Research Program (NCORP). The ACR Center for Research and Innovation™ manages trial implementation at TMIST sites.

“Finding and enrolling a large enough sample size within a reasonable time can be difficult in randomized clinical trials, especially when targeting a specific population. By setting records for the diversity and scope of TMIST, the cancer cooperative groups have proven we are the ideal setting for large-scale screening and prevention trials,” said ECOG-ACRIN Group Co-Chair Mitchell D. Schnall, MD, PhD (pictured at left).

The collaborating cooperative groups consist of the Alliance for Clinical Trials in Oncology, the Canadian Cancer Trials Group, the ECOG-ACRIN Cancer Research Group, NRG Oncology, and the SWOG Cancer Research Network. These groups design and conduct clinical trials through the NCI National Clinical Trials Network (NCTN).