Most women diagnosed with early-stage breast cancer do very well after surgery and receiving treatments tailored to their risk of recurrence (their risk that the cancer will come back after treatment). For instance, the 5-year survival rate is nearly 100% for hormone receptor–positive (HR+), HER2-negative (HER2-) breast cancer that has not spread to the lymph nodes.[i] Reaching the 5-year mark is often seen as a major milestone. If breast cancer is going to return, it often does so within those first 5 years.

However, some relapses happen later—sometimes 10, 15, or even 20 years or more after treatment. Many patients are unaware of this long-term risk.

A new research study called EA1241, led by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN), is enrolling women who took part in two earlier breast cancer clinical trials and later experienced recurrences. The study is also enrolling women from these trials who have not had recurrences but remain at high risk. The study aims to understand why breast cancer cells can sometimes lie dormant (sleeping) for long periods of time—and what may trigger them to “wake up” and begin growing again.

Research suggests that three main factors seem to influence how cancer cells behave over time:

• Changes in cancer cell DNA
• The body’s immune system
• The tumor microenvironment (the mix of non-cancerous immune cells and blood vessels that surround cancer cells)

Studying these factors is challenging because it requires long-term check-ups on patients. It also requires access to tumor samples from the original cancer and any later recurrences.

EA1241 is designed to address these challenges. The study will create a shared research collection, called a biobank, made up of tissue samples collected during earlier clinical trials. It will also contain health information gathered from participants over the next 5 years. Researchers plan to apply the latest, most advanced research technologies to these resources.

The study builds on two large and influential breast cancer trials—TAILORx and RxPONDER—which involved nearly 15,000 participants with early-stage HR+, HER2- breast cancer. In these trials, tumors were removed during surgery and tested using the Oncotype DX Breast Recurrence Score®. By using this test, the trials demonstrated that most women with early-stage, node-negative (TAILORx) and many with node-positive (RxPONDER) breast cancer can safely avoid chemotherapy.

The EA1241 study will enroll about 600 people. Eligible participants include:

• Individuals from TAILORx or RxPONDER who later experienced breast cancer recurrences
• RxPONDER participants who were not able to continue in that trial due to a high recurrence score (26–100), even if breast cancer has not returned (a high score indicates a greater recurrence risk, and studying these cases may provide important insights)

Participation in EA1241 is designed to be simple. Patients do not need to have a new biopsy. They will have one visit with their oncologist each year for 5 years to collect health information for research. These visits can take place in person, by phone, or through telemedicine. EA1241 is an observational study, meaning researchers will track participants' health over time without changing their standard treatment.

ECOG-ACRIN is partnering with Caris Life Sciences and the Curtis Laboratory at Stanford University to perform advanced molecular testing on the biobank samples. This testing will examine the genetic makeup of tumor cells in great detail. It will compare participants’ tissue samples at diagnosis with their relapse samples to identify changes over time. These analyses are expected to generate highly detailed data that have not previously been available.

The goal of this study is to discover genetic and biological factors that play a role in breast cancer’s return. A better understanding of these factors could help improve risk assessment and guide the development of new treatments and strategies to prevent recurrence.

People who participated in TAILORx and RxPONDER and are interested in EA1241 should talk with their oncologist.

Learn more about EA1241 at ecog-acrin.org.

Related:

Video: Rima Patel, MD, lead researcher, discusses the EA1241 research study

Come again? Communicating clearly about risk of recurrence after early-stage breast cancer

[i] Female breast cancer — cancer stat facts. SEER, National Cancer Institute. Accessed January 26, 2026. https://seer.cancer.gov/statfacts/html/breast.html