BRCA1, BRCA2, TP53 and ATM gene mutations are the most studied tumour suppressor genes (TSGs) influencing the loco-regional approach to breast cancer (BC). Due to altered radio sensitivity of mutated cancer cells, mastectomy has always been advised in most patients with BC linked to TSGs mutations in order to avoid or minimize the use of adjuvant radiotherapy (ART). Whether ART is safe or not in these carriers is still debated. As a result, this issue has been widely discussed in the recent ASTRO and ASCO papers, yielding important and useful recommendations on the use of ART according to the mutational status. In this review, we have highlighted the impact of these mutations on local control, toxicities, second tumors, and contralateral breast cancers (CBCs) after ART to solve remaining doubts and encourage the safe use of ART when indicated.
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