The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN), in collaboration with the SWOG Cancer Research Network (SWOG), has launched a new initiative to analyze paired original and recurrent tumor specimens from two practice-changing breast cancer clinical trials. Through the translational study EA1241, researchers will search for biological and genetic factors in tumors that may drive recurrences 10 to 20+ years after personalized treatment. Caris Life Sciences® will perform comprehensive sequencing and molecular profiling of specimens using MI Cancer Seek®.
"What drives an incurable late recurrence of breast cancer in other parts of the body years after the initial diagnosis remains an unsolved mystery," said lead investigator Joseph A. Sparano, MD, who led the landmark TAILORx trial and directs clinical research operations at the Mount Sinai Tisch Cancer Center in New York. "But by applying the newest molecular technologies and artificial intelligence (AI) to study tumor samples, we have an unprecedented opportunity to unlock these mysteries and prevent cancer from ever recurring."
The initiative builds on two pivotal clinical trials, ECOG-ACRIN's TAILORx and SWOG's RxPONDER, which transformed breast cancer treatment for patients with the most common subtype: early-stage, hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-). These trials demonstrated that many patients can safely avoid chemotherapy when guided by clinical factors and the 21-gene recurrence score assay, known as the Oncotype DX Breast Recurrence Score® (RS). TAILORx validated the assay in node-negative disease, and RxPONDER extended that validation to node-positive disease.
The National Cancer Institute (NCI), one of the U.S. National Institutes of Health, funded both of these clinical trials, which were conducted through its National Clinical Trials Network (NCTN). The NCI also funded the collection and biobanking of associated tissue specimens during the trials.
Together, the trials enrolled more than 15,000 patients and generated one of the world's largest breast cancer tissue banks. This collection is part of a broader cooperative group specimen banking program that serves as a cornerstone of translational science-linking high-quality, clinically annotated tumor samples with long-term patient outcomes.
"There are very few clinical trial cohorts in the world that allow direct molecular comparison of original tumors and matched relapse specimens from the same patients, linked to long-term prospective outcomes. TAILORx and RxPONDER followed patients for years after carefully defined adjuvant therapy, giving us a rare opportunity to study late recurrence within a well-characterized clinical framework," said co-investigator Kevin Kalinsky, MD, MS. Dr. Kalinsky led the RxPONDER trial for SWOG and directs the Division of Medical Oncology at the Winship Cancer Institute of Emory University in Atlanta.
EA1241 aims to extend the scientific impact of the original trials by creating a long-term discovery platform to study tumor evolution and resistance biology. The study will enroll 600 TAILORx and RxPONDER participants who have either experienced a recurrence of breast cancer or remain at high risk based on a high genomic score (RS >26). Participants will consent to ECOG-ACRIN retrieving their recurrence specimens for the biorepository and will provide clinical information annually for 5 years through visits to the oncologist.
Patients from TAILORx and RxPONDER already helped change clinical practice, and by contributing to this research, they are helping shape the next generation of breast cancer science-research that could explain late recurrence and point to new prevention strategies."
Rima Patel, MD, co-investigator, breast oncologist, Tisch Cancer Center
Early-stage breast cancer comprises a large and diverse group of patients, and treatment decisions frequently hinge on the uncertain risk of recurrence. In the United States, it is estimated that approximately 321,910 new cases of breast cancer will be diagnosed in 2026, with about 60% detected at an early stage (American Cancer Society). This underscores the broad application and clinical relevance of more accurate and personalized risk assessments.
EA1241 is funded by the Department of Defense Congressionally Directed Medical Research Programs. The NCI supports the effort by permitting the use of the NCTN infrastructure to conduct the study as part of a collaborative arrangement.
ECOG-ACRIN and Caris Life Sciences® will perform the planned molecular analyses through their long-term public-private partnership. Caris' MI Cancer Seek® integrates whole exome and whole transcriptome profiling, whole slide imaging, and advanced machine learning analyses.
Dr. Sparano presented initial findings from the partnership at the 2025 San Antonio Breast Cancer Symposium regarding a new tumor gene panel developed from TAILORx data: Multimodal Artificial Intelligence (AI) models Integrating Image, Clinical, and Molecular Data for Predicting Early and Late Breast Cancer Recurrence in TAILORx. This assay demonstrated improved prognostic performance compared with the 21-gene recurrence score, suggesting its potential for more personalized treatment decision-making in early-stage breast cancer. A manuscript is in development.
"Our public-private partnership with Caris has deep roots, aligned interests, and a commitment to develop the best science in the service of early detection and treatment of cancer. By engaging state-of-the-art molecular testing and interpretation, we take another step toward treatment informed by the individual patient's risk profile," said ECOG-ACRIN group co-chair Peter J. O'Dwyer, MD.
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