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Abstract PS15-06: The distribution of radiosensitivity index differs by PAM50 subtype in primary breast tumors

Background: Prior studies identified radiosensitive and radioresistant breast tumor phenotypes and demonstrated that gene-expression signatures such as the radiosensitivity index (RSI) can be used to derive biologically rational radiation dose selection. In this study, we assessed the RSI of primary breast tumor samples and its association with PAM50 subtype.Materials/Methods: Primary breast tumor samples were identified from a multi-institutional tissue biorepository. Tumors were excluded if they were treated with neoadjuvant therapy or had distant metastatic disease at the time of sample collection. The RSI gene signature and PAM50 subtype were assessed through transcriptomic profiling performed on Affymetrix microarray chips. Distribution of RSI values across PAM50 subtypes was assessed with the Kruskal-Wallis test. Differences in proportions of radioresistant and radiosensitive tumors among PAM50 subtypes were assessed with the Chi-squared test, where radioresistant was defined as RSI>0.3745 based on prior studies. Clinicopathologic characteristics were obtained through clinical chart review. Results: A total of 637 primary breast tumors with available genomic profiling and clinical information were included for analysis. HIstologies were predominantly invasive ductal carcinoma (81.5%) and invasive lobular (11.6%). Most tumors were T1-T2 (91.7%) while 35.9% had pathologically positive lymph nodes. The distribution of RSI significantly differed by PAM50 classification (Kruskal-Wallis p Conclusion: Breast tumor PAM50 subtypes demonstrate significant variation in radiosensitivity. Further studies are needed to determine if genomic subtyping can refine the ability to predict clinical radiation response and further optimize individual therapy. Citation Format: Matthew Fahey, Nicholas Russo, Casey Liveringhouse, Matthew Mills, Kamran Ahmed, Roberto Diaz. The distribution of radiosensitivity index differs by PAM50 subtype in primary breast tumors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-06.