Recent Advances in Optimizing Radiation Therapy Decisions in Early Invasive Breast Cancer

SIMPLE SUMMARY: Radiation therapy is routinely prescribed for women who undergo breast-sparing surgery for early breast cancers. Over the years, advancements in diagnosis and treatments have dramatically improved breast cancer outcomes, now approaching 100% survival at 5 years for those diagnosed at stage I with favorable clinical and molecular features. In this review, we discuss the investigations that are underway to identify women with low-risk cancers in whom radiation therapy can either be completely avoided or delivered in lower intensities. We also review ongoing clinical trials that are assessing if radiation therapy can increase the capacity of patients’ anticancer immune responses and discuss if cancer cells that are shed in the blood can guide radiation decisions. ABSTRACT: Adjuvant whole breast irradiation after breast-conserving surgery is a well-established treatment standard for early invasive breast cancer. Screening, early diagnosis, refinement in surgical techniques, the knowledge of new and specific molecular prognostic factors, and now the standard use of more effective neo/adjuvant systemic therapies have proven instrumental in reducing the rates of locoregional relapses. This underscores the need for reliably identifying women with such low-risk disease burdens in whom elimination of radiation from the treatment plan would not compromise oncological safety. This review summarizes the current evidence for radiation de-intensification strategies and details ongoing prospective clinical trials investigating the omission of adjuvant whole breast irradiation in molecularly defined low-risk breast cancers and related evidence supporting the potential for radiation de-escalation in HER2+ and triple-negative clinical subtypes. Furthermore, we discuss the current evidence for the de-escalation of regional nodal irradiation after neoadjuvant chemotherapy. Finally, we also detail the current knowledge of the clinical value of stromal tumor-infiltrating lymphocytes and liquid-based biomarkers as prognostic factors for locoregional relapse.