Insights into the theranostic value of precision medicine on advanced radiotherapy to breast cancer

Abstract

Breast cancer is the most common cancer in women worldwide. "Breast cancer" encompasses a broad spectrum of diseases (i.e., subtypes) with significant epidemiological, clinical, and biological heterogeneity. Each of these subtypes has a different natural history and prognostic profile. Although tumour staging (TNM classification) still provides valuable information in the overall management of breast cancer, the current reality is that clinicians must consider other biological and molecular factors that directly influence treatment decision-making, including extent of surgery, indication for chemotherapy, hormonal therapy, and even radiotherapy (and treatment volumes). The management of breast cancer has changed radically in the last 15 years due to significant advances in our understanding of these tumours. While these changes have been extremely positive in terms of surgical and systemic management, they have also created significant uncertainties concerning integration of local and locoregional radiotherapy into the therapeutic scheme. In parallel, radiotherapy itself has also experienced major advances. Beyond the evident technological advances, new radiobiological concepts have emerged, and genomic data and other patient-specific factors must now be integrated into individualized treatment approaches. In this context, "precision medicine" seeks to provide an answer to these open questions and uncertainties. Although precision medicine has been much discussed in the last five years or so, the concept remains somewhat ambiguous, and it often appear to be used as a "catch-all" term. The present review aims to clarify the meaning of this term and, more importantly, to critically evaluate the role and impact of precision medicine on breast cancer radiotherapy. Finally, we will discuss the current and future of precision medicine in radiotherapy.

Keywords: breast cancer; precision medicine; radiosensitivity; radiotherapy; radiotherapy regime.

Figure 1

Intertumor genetic heterogeneity in breast cancer. At the genomic level, breast cancers are remarkably heterogeneous and no two tumors display an identical constellation of somatic mutations. A) Venn diagram illustrates the significantly mutated genes in breast cancer identified in different sequencing studies. B) Mutational frequencies of the 100 most frequently mutated genes in all breast cancers, illustrating the small number of genes highly recurrently mutated and a long “tail” of genes with low mutational frequency. C) The mutational frequencies of the 20 most frequently mutated genes in breast cancers of luminal A, luminal B, HER2-enriched and basal-like “intrinsic” subtypes. TCGA: The Cancer Genome Atlas .

Figure 2

Precision medicine and radiotherapy. Patients could be stratified into different cohorts based on predicted intrinsic radiosensitivity and risk of toxicity. On-treatment monitoring may provide information on response to treatment, enabling adaptive changes to a patient's treatment to be made if necessary. Post-treatment biomarkers could be used to assess for evidence of toxicity, tumor recurrence or the development of metastatic disease .