Breast cancer (BC) is the most common tumor and the second cause for cancer-related death in women worldwide, although combined treatments are well-established interventions. Several effects seem to be responsible for poor outcomes in advanced or triple-negative BC patients. Focusing on the interaction of ionizing radiation with tumor and normal tissues, the role of cytokine modulation as a surrogate of immunomodulation must still be explored. In this work, we carried out an overview of studies published in the last five years involving the cytokine profile in BC patients undergoing radiotherapy. The goal of this review was to evaluate the profile and modulation of major cytokines and interleukins as potential biomarkers of survival, treatment response, and toxicity in BC patient undergoing radiotherapy. Out of 47 retrieved papers selected using PubMed search, 15 fulfilled the inclusion criteria. Different studies reported that the modulation of specific cytokines was time- and treatment-dependent. Radiotherapy (RT) induces the modulation of inflammatory cytokines up to 6 months for most of the analyzed cytokines, which in some cases can persist up to several years post-treatment. The role of specific cytokines as prognostic and predictive of radiotherapy outcome is critically discussed.