Microscopic image of breast cancer cells – Generated with Google Gemini AI
A newly launched randomized controlled trial is investigating a personalized approach to neoadjuvant therapy for a subset of patients with early-stage breast cancer, aiming to replace standard chemotherapy with endocrine therapy in a selected population.1
The TEODOR trial, sponsored by the Austrian Breast & Colorectal Cancer Study Group (ABCSG), will use circulating tumor DNA (ctDNA) testing and endocrine responsiveness to guide treatment decisions for women with hormone receptor-positive (HR+), HER2-negative breast cancer.
The phase 2, multicenter trial (NCT07084558) is designed to identify patients who may safely forgo neoadjuvant chemotherapy, a treatment regimen that can cause significant short- and long-term side effects. The study will enroll approximately 250 patients across 15 sites in Austria and is a collaborative effort between ABCSG and Natera, the company that developed the personalized ctDNA test.
The core of the TEODOR trial’s strategy is to leverage the excellent outcomes observed in previous studies for patients who test negative with the circulating tumor DNA test, Signatera, at the time of diagnosis and subsequently receive chemotherapy. These patients have demonstrated a risk of recurrence of less than 5%. The current study seeks to determine if a less toxic, yet equally effective, alternative exists for this favorable-prognosis group.
The trial’s protocol involves an initial 4-week course of endocrine therapy. Following this period, patients who remain ctDNA-negative and demonstrate a favorable endocrine sensitivity—as measured by the Ki-67 proliferation index—will be randomized into 2 arms. One arm will continue with additional endocrine therapy, while the other will proceed with standard chemotherapy. This design is intended to directly compare the efficacy of these 2 treatment strategies in the preselected patient population.2
The primary end point of the TEODOR trial is the rate of neoadjuvant therapy response. This will be assessed using both pathological complete response and the modified Preoperative Endocrine Prognostic Index (PEPI) score. These metrics are well-established indicators of treatment efficacy and are crucial for evaluating the potential of the personalized approach. The study will also track secondary end points, including critical long-term outcomes such as breast cancer recurrence and overall survival, which are essential for confirming the durability and safety of the endocrine-only approach.
“TEODOR is designed to examine whether we can use endocrine responsiveness and ctDNA status to optimize systemic therapy in the neoadjuvant setting,” said ABCSG president Michael Gnant, MD, FACS, FEBS, who serves as professor of surgery, Comprehensive Cancer Center, Medical University of Vienna, and principal investigator of the TEODOR trial.1 “This study marks a critical step toward more personalized medicine, leveraging the latest technologies to improve patient care.”
This trial reflects a growing trend in oncology to move beyond a one-size-fits-all approach to treatment. By using molecular and biological markers, clinicians can better stratify patients and tailor therapies to maximize efficacy while minimizing toxicity. The potential for a significant portion of patients with early-stage, HR+/HER2– breast cancer to avoid chemotherapy would represent a major clinical advancement. The endocrine therapy-only approach could lead to a better quality of life for these patients during treatment, with fewer side effects such as nausea, hair loss, and the risk of long-term complications like cardiotoxicity or neuropathy.
“With the TEODOR trial, our goal is to identify patients who may be able to safely forgo chemotherapy,” said Angel Rodriguez, MD, medical director of oncology at Natera. “We are proud to collaborate with ABCSG on this important trial, and we hope this study will support the role of Signatera in guiding neoadjuvant therapy in breast cancer.”