Since the beginning of the Tomosynthesis Mammographic Imaging Screening Trial (TMIST) in 2017, enrollment has steadily increased. And, despite the ongoing pandemic, enrollment has actually doubled within the past 17 months—with African American women now comprising 20 percent of the study population. More than halfway to its recruiting goal of 128,905 participants, recruitment of women from diverse backgrounds is vital to ensuring that TMIST trial results will be applicable across races, ethnicities, and underserved communities.

Led by the ECOG-ACRIN Cancer Research Group, TMIST is the first randomized trial that identifies women for whom digital breast tomosynthesis, known as 3-D mammography, may outperform digital (2D) mammography in reducing advanced cancers. The study emphasizes the comparative effects of the two technologies with tomosynthesis as the newer technology of the two. It will assess whether tomosynthesis reduces advanced breast cancer over time, and whether screening with tomosynthesis reduces the cancers more likely to lead to a woman’s death.

“The primary TMIST study question is whether tomosynthesis is more sensitive for those breast cancers that are more likely to lead to a woman’s death from breast cancer,” said Etta Pisano, MD, FACR, TMIST study chair and Chief Research Officer of the American College of Radiology (ACR). “Does tomosynthesis screening lead to a reduction in the aggressive cancers because they are found earlier (e.g., triple-negative breast cancer [TNBC])? If TMIST finds that reduction in aggressive cancers, it would suggest tomosynthesis is saving more lives than the older technology.”

TNBC is an aggressive breast cancer subtype that disproportionately affects BRCA1 mutation carriers and young women of African origin. Additionally, evidence has shown that African American women with TNBC have worse clinical outcomes than women of European descent, according to the National Institutes of Health.

Incentives to Enhance Representation

While enrollment initially dropped during the beginning of the COVID-19 pandemic, participation rebounded in January 2021 to record levels with minority participation continuing to increase due to special incentives to enhance the representation of underserved populations. These include TMIST coverage of exams for many uninsured or underinsured women, free exams, and complementary transportation. Additional benefits to the program included promotion by the National Medical Association (the collective voice for physicians of African descent), and advanced payment to qualifying sites to fund dedicated research staff as they begin TMIST participation.

TMIST is one of the most effective National Cancer Institute (NCI)-funded trials in generating more participation within the African American population, noting the more than 20 percent participation rate compared to the average cohort in NCI-funded trials, which is approximately 9 percent.

National & Local Collaboration

A strong effort by national associations (ACR and others) in collaboration with local providers to encourage women to reconnect for their regular breast cancer screening has resulted in effective, personalized recruiting of women to take part in TMIST by staff at local facilities.

“TMIST sites are effectively reaching women in their communities, especially Women of Color, to gain a study population able to provide needed data to move breast cancer screening and health equity forward,” said Pisano. “We’re recruiting about 2,000 women per month at present.”

Currently, more than 69,000 women are enrolled in TMIST at 122 study sites in the U.S. and abroad. About 30 more sites around the world are still working to open the clinical trial. Of the accredited mammography scanners in the U.S., only 45 percent are 3D units; approximately 20 percent of imaging facilities in the U.S. do not have 3D scanners.

“Many of these sites may be in underserved areas,” said Pisano. “One study shows African American women are far less likely to be screened with digital breast tomosynthesis than those of European or Asian descent.”

Since 2012, African American women are developing breast cancer at the same rate as those of European descent; however, the death rate is higher among African American women, she added.

To educate and promote the study on a global scale, a wide variety of educational and recruitment materials are distributed to the sites and translated into multiple languages (e.g., English, Spanish, Chinese Simplified, Korean, and Vietnamese), including written scripts for phone callers, clinic posters, and written/printed cards to be mailed. Local facilities are specifically tailoring their recruitment programs to address the needs and concerns of the communities they serve, such as helping African American women to overcome fears about donating biospecimens for medical research.

“The trial’s screening sites are not just based in academic settings, but [also] in sites already serving diverse populations, which brings familiarity, trust, and a higher comfort level,” Pisano noted.

Future Applications

An important TMIST goal is the development of individualized screening strategies to reduce breast cancer’s impact on women not as well served by current screening strategies.

“In the future, we’d like to see a screening option based on an algorithm in which the doctors and/or patients can input their health data to receive an individualized assessment,” Pisano stated.

To help researchers discover ways to tailor future screening to a woman’s individual risk, the study is creating a large, curated dataset of breast cancer screening clinical data, images, and biospecimens. The data collected through TMIST will lead to better, individualized screening strategies based on each woman’s risk factors.

“We are creating a biorepository to collect genetic information through the donation of blood and/or spit samples from study volunteers, which, along with other TMIST data, will allow us to develop highly personalized screening strategies, knowing that breast cancer risk increases with age depending on the density of breast tissue, hormones, and genetic disposition,” Pisano explained.

In addition to TMIST sites in the U.S., women are encouraged to participate at sites in Canada, South America, Italy, and Korea. In addition, trial leaders continue to seek approximately 30 new sites to participate. So that TMIST can have greater geographic diversity along with racial and ethnic diversity, trial leaders would like to add sites in the upper/northern Rocky Mountain and Northern Plains regions—including Montana, Wyoming, North Dakota, and South Dakota—as well as Oklahoma, Kansas, and Missouri. Pisano stated that there is a need to add sites that serve Native American and Asian communities.

“Considering the high mortality rates among individuals in these populations, TMIST is on the right track towards helping us understand the predictive factors of breast cancer. This information will be important to improve early detection for as many women as possible,” said Edith Peterson Mitchell, MD, MACP, FCPP, FRCP, Co-Chair of the ECOG-ACRIN Health Equity Committee; Clinical Professor of Medicine and Medical Oncology at Thomas Jefferson University; and Associate Director for Diversity Programs and Director of the Center to Eliminate Cancer Disparities for Sidney Kimmel Cancer Center at Jefferson. “By covering exams for women with inadequate insurance, TMIST enables researchers to gauge screening effectiveness across patient groups and care settings.”

The leaders of TMIST, which began in 2017, aim to conclude enrollment by the end of 2024 with several years of follow-up into 2027.

“In the meantime, I strongly encourage imaging facilities that have three-dimensional (3D) mammography and digital (2D) mammography, particularly those in rural, inner city, and other underserved communities, to take part in TMIST,” Mitchell emphasized. “Sites must have both technologies and the ability to effectively communicate with the women they serve to recruit them to take part in the trial. However, practices need not be long-time participants in clinical trials. TMIST staff can walk sites through the registration process and help them efficiently get up and running.”

Amy Gallagher is a contributing writer.