Radiogenomics and Phenotype Presentation of Breast Cancer with a Special Focus on High-Risk Women

Abstract

Breast cancer is a diverse collection of diseases with varying clinical presentations, subtypes, and treatment responses. In the past decade, gene-expression profiling has revolutionized breast cancer classifications, and the traditional classifications based on immunohistochemistry have been replaced by molecular subtype profiles. Breast cancer has four distinct molecular subtypes: luminal A; luminal B; human epidermal growth factor receptor 2 (HER2)-enriched; and basal-like. These subtypes are unevenly distributed among women with breast cancer and demonstrate distinct differences in tumor phenotypic presentations. In addition, each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes; and currently, subtype-based recommendations for systemic therapies for breast cancer are used in clinical practice. As medical research and therapy have entered the genomic era in which personalized approaches toward treatment are being explored, diagnostic tests need to be equally multilayered and complex to be able to identify the relevant genetic alterations that render cancers susceptible to treatment. Medical imaging has always been an integral part of disease diagnosis and treatment decisions. With significant advances in imaging techniques, image analysis, along with the development of high-throughput methods to extract and correlate multiple imaging parameters with genomic data, has heralded a new direction in medical research. Radiogenomics is a novel approach, which aims to correlate imaging characteristics (i.e., the imaging phenotype) with gene expression patterns, such as molecular subtypes, gene mutations, and other genome-related characteristics. Radiogenomics is designed to facilitate a deeper understanding of molecular tumor biology through the extraction of parameters derived from image processing and analyses of medical images that are linked to the geno- and phenotypic characteristics of the tissue. Due to the non-invasive nature of medical imaging and its ubiquitous use in clinical practice, the field of radiogenomics is rapidly evolving and initial results are encouraging. In this article, we will review the phenotypic presentation of breast cancer, briefly discuss the background and methodology of radiogenomics of breast magnetic resonance imaging (MRI), and then summarize the current role for radiogenomics, as well as its potential, with a special focus on high-risk women.