Affecting one in 8 women, breast cancer is the second most common cancer in women in the United States. In 2019, 42,280 deaths were reported as a result of breast cancer. The standard of care for treatment is surgical tumor excision with sentinel lymph node biopsy and adjuvant radiation therapy. Although this standard procedure significantly improved tumor-free survival rate, 10-12% of patient morbidity is reported due to radiation-induced tissue fibrosis (RIF). To date, very little is known about its etiologies. To bridge this knowledge gap, this study was designed to understand the differences in RNA expression between radiated and non-radiated breast tissues using RNA sequencing techniques and immunohistochemistry (IHC). Using the approved Institutional Review Board protocol (University of Utah: 00047788), those patients who elected to undergo a double mastectomy but only had radiation therapy to the affected single breast were recruited. Post-radiation therapy, tissue samples (skin, fibrous capsule, and muscle) were collected from both breasts, the total RNAs were extracted, and a complete sequencing study was performed. Post-processing, the differentially expressed genes (DEGs) were identified, and their abilities to over and under-translate the corresponding proteins were validated using IHC. The data did confirm the over- and under-translations of respective proteins. This pilot data clearly indicates the utilities of complete RNA sequencing in understanding the mechanisms of RIF.