Genomic Molecular Profiling in Breast Cancer: Transforming Radiation Decision-Making Through Precision Medicine

This review will discuss the development of various molecular and radiation-specific genomic signatures, their use in clinical settings, and challenges that impede their widespread clinical implementation as well as future directions towards tailored radiation-decision making in women with invasive and non-invasive breast cancer. A summary of the newly published and ongoing clinical trials that use genomic signatures to guide radiation decisions will be provided. We highlight the further use of molecular profiling in radiation therapy and the ongoing studies validating their utility in guiding radiation de-escalation trials as well as treatment intensification studies. Herein we explore the evolution and implementation of genomic and radiation-specific molecular signatures in breast cancer treatment. We highlight the potential of these signatures to refine radiation therapy (RT) decisions, enabling the personalization of treatment strategies that align with each patient's unique molecular signature. The review covers the development and validation of various gene expression signatures, such as the Radiosensitivity Index (RSI), GARD, and POLAR, which are designed to predict radiation response and benefit. We also examine recent clinical trials that have incorporated these genomic tools, particularly in efforts to de-escalate or omit RT for low-risk patients. Despite the advancements made in this area, there remains a need for further clinical validation and discussion of the challenges of implementing these technologies in routine clinical practice, especially in resource-limited settings.