4D Path unveiled groundbreaking research at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, demonstrating that its proprietary QPOR platform can accurately identify breast cancer patients likely to respond to neoadjuvant chemotherapy, even among those with low stromal tumor-infiltrating lymphocytes (TILs)—a population traditionally considered treatment-resistant.
The study represents a significant breakthrough in precision oncology, challenging long-held assumptions about patient selection for chemotherapy and offering new hope to previously underserved breast cancer populations.
Revolutionary Predictive Capabilities
Using routine pre-treatment biopsy images, 4D Path's QPOR platform analyzed data from 88 HER2-negative germline BRCA carriers enrolled in the INFORM (TBCRC031) clinical trial. The research was conducted in partnership with leading institutions including Brigham and Women's Hospital, Dana-Farber Cancer Institute, and Beth Israel Deaconess Medical Center.
The results demonstrated remarkable predictive accuracy. Among patients with low TILs, those identified as having low immune heterogeneity using the QPOR Immune Heterogeneity Index (IHI) achieved a 66% response rate to neoadjuvant chemotherapy, compared to just 25% among those with high heterogeneity.
Exceptional Results in Triple-Negative Breast Cancer
The findings were particularly striking in Triple-Negative Breast Cancer (TNBC), an aggressive subtype known for poor treatment outcomes. Patients with low TILs and low heterogeneity demonstrated a 74% response rate, remarkably outperforming even those with high TILs who achieved a 50% response rate.
Across the entire study cohort, low immune heterogeneity emerged as a more powerful predictor of treatment response than TIL levels alone, fundamentally challenging current biomarker approaches.
Clinical Impact and Expert Perspectives
"The 4D Path QPOR platform provides a unique, objective, and biologically based system for assessing prognosis and predicting response to therapy in a variety of tumor types," said Dr. Stuart J. Schnitt, Chief of Breast Oncologic Pathology at Dana-Farber/Brigham and Women's Cancer Center. "In this study, the platform was able to predict the likelihood of response to neoadjuvant chemotherapy in breast cancer patients with BRCA1 and 2 germline mutations."
Dr. Schnitt emphasized the novelty of the approach: "To my knowledge, this is the first time that heterogeneity of TILs distribution provides predictive information beyond that of quantifying TILs alone. If these results can be validated in other populations of breast cancer patients, the QPOR platform could become a novel means to help oncologists determine which patients are more or less likely to respond to treatment."
Transforming Treatment Paradigms
The research has far-reaching implications for clinical practice. Historically, patients with low TILs were often steered away from chemotherapy due to assumptions about poor response likelihood. 4D Path's findings directly challenge this approach, potentially opening new treatment avenues for a previously underserved patient population.
"The predictive capacity of the QPOR biomarker of immune heterogeneity to identify responders who harbor low baseline immune infiltrates is an important moment for 4D Path," explained Satabhisa Mukhopadhyay PhD, Co-Founder, Co-Inventor, and Chief Scientific Officer of 4D Path. "By quantifying the hidden dynamics of cancer directly from routine biopsy images, we deliver a deeply personalized, computational view of collective tumor states, including cell cycle deregulation and immune microenvironment interactions."
Advanced Platform Technology
The patented Q-Plasia OncoReader (QPOR) platform represents a significant technological advancement in cancer diagnostics. The system directly computes cell cycle deregulation and tumor microenvironment dynamics from standard biopsy images, enabling precision treatment selection previously impossible with conventional approaches.
Mukhopadhyay noted that immune heterogeneity information, often a key factor in drug resistance, can be translated by the QPOR platform into actionable insights that drive more targeted and effective patient care approaches.
The breakthrough research positions 4D Path's technology as a potential game-changer in breast cancer treatment selection, offering clinicians a powerful new tool to identify treatment responders in populations previously considered unlikely to benefit from chemotherapy.
