Precision Oncology Advancement: Natera and MEDSIR's MiRaDoR Initiative Reshapes HR+/HER2- Breast Cancer Management

Strategic Partnership Leverages Cell-Free DNA Technology for Treatment Innovation

Natera, a pioneering force in cell-free DNA diagnostics and precision medicine, has joined forces with MEDSIR, a globally recognized oncology research organization, to launch a groundbreaking phase II multicenter investigation into hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer treatment strategies. The MiRaDoR study (NCT05708235) represents a significant shift in how clinicians approach early-stage disease management by integrating molecular profiling with targeted therapeutic approaches.

Understanding the Clinical Challenge

Breast cancer remains the most prevalent malignancy among women globally, with approximately 2.3 million new cases documented in 2022. However, the complexity intensifies when examining HR+/HER2- disease specifically—a subset accounting for roughly 70% of all breast cancer diagnoses. Despite therapeutic advances, disease recurrence continues to pose substantial challenges for this patient population, underscoring the need for more refined treatment strategies and predictive biomarkers.

The MiRaDoR Trial Structure: Four-Arm Comparative Design

Funded by F. Hoffman-La Roche Ltd. and directed by MEDSIR, the MiRaDoR trial will enroll up to 60 patients who demonstrate Signatera positivity without clinical or radiological evidence of recurrent disease. The sequential arm assignment strategy includes:

• Arm A (Control): Standard endocrine therapy for 90 days, with subsequent transition to comparative arms
• Arm B: Giredestrant monotherapy, an oral selective estrogen receptor degrader
• Arm C: Giredestrant combined with Abemaciclib, a CDK4/6 inhibitor
• Arm D: Giredestrant combined with Inavolisib for PIK3CA-mutated patients, targeting phosphatidylinositol 3-kinase signaling

Molecular Residual Disease as the Primary Endpoint

The trial’s innovative framework centers on serial circulating tumor DNA (ctDNA) assessment as both a surveillance and predictive tool. The primary endpoint measures the proportion of participants achieving a 90% decrease or complete clearance of baseline ctDNA within the initial three-month treatment window. Extended monitoring occurs at 6, 9, and 12 months, then biannually through study completion.

Redefining Clinical Trial Standards

According to Angel Rodriguez, M.D., senior medical director of oncology at Natera, this collaboration exemplifies how precision oncology has evolved. By integrating Signatera Genome’s molecular residual disease detection capability with genomic characterization—particularly PIK3CA mutation assessment—the trial moves beyond traditional surveillance paradigms. Rather than simply asking whether cancer has recurred, investigators now address the fundamental question: which therapeutic combination most effectively suppresses molecular disease markers?

International Expansion and Study Timeline

Enrollment has already commenced, with several U.K. sites currently active. Additional European site openings are anticipated throughout 2026, positioning this investigation to potentially reshape treatment algorithms for HR+/HER2- breast cancer across multiple regions.

About the Partner Organizations

Natera operates as a leader in cell-free DNA and precision medicine, maintaining ISO 13485-certified laboratories across Austin, Texas and San Carlos, California, with an additional ISO 27001-certified facility through its subsidiary Foresight Diagnostics in Boulder, Colorado. MEDSIR, established in 2012, specializes in end-to-end clinical trial management with operational presence in Spain, the United States, and a strategic partnership with Oncoclínicas in Brazil, strengthening research capabilities across the Americas.