Abstract：
Many breast cancer (BC) predisposition genes encode proteins involved in DNA damage repair (DDR). Identification of germline pathogenic va-riants (PV) in DDR genes raises the question whether their presence can influence the treatment outcomes and potential radiation-induced toxicity in their carriers treated by adjuvant radiotherapy, which has not yet been answered conclusively. We retrospectively examined records of 213 BC patients treated by adjuvant radiotherapy, including 39 (18.3 %) BRCA1/2 PV carriers, 25 carriers (11.7 %) of PV in other breast cancer-predisposing genes, and 149 (70 %) non-carriers. Our goal was to examine 5-year disease-free survival (5y DFS) rates among the study groups and determine the impact of radiotherapy-induced lymphopoenia (RIL) on this outcome. While we found no significant difference in 5y DFS between non-carriers and carriers of BRCA mutations (86.4 % vs 78.4 % P = 0.24) or between non-carriers and other studied mutations (86.4 % vs 93.3 %; P = 0.27), respectively, we observed that the entire group of PV carriers had a significantly lower proportion of patients without RIL (P = 0.04) than the non-carriers. In contrast, subsequent analyses indicated a non-significant trend toward an increased 5y DFS in PV carriers with RIL. Our single-centre study indicated that the presence of PV in BC patients has an insignificant impact on DFS but can reduce the risk of RIL associated with adjuvant radiotherapy. It remains unclear whether this may result from the paradoxical activation of anti-tumour immunity in PV carriers with higher lymphocyte consumption resulting from higher immune effectiveness.
摘要：
许多乳腺癌（BC）易感性基因编码参与DNA损伤修复（DDR）的蛋白质。鉴定DDR基因中的种系致病因子（PV）提出了一个问题，即它们的存在是否会影响通过辅助放疗治疗的携带者的治疗结果和潜在的辐射诱导毒性。这还没有得到决定性的回答。我们回顾性地检查了213例接受辅助放疗的BC患者的记录，包括39家(18.3%)BRCA1/2光伏运营商，其他乳腺癌易感基因中25例PV携带者（11.7%），和149（70％）非携带者。我们的目标是检查研究组的5年无病生存率（5yDFS），并确定放疗引起的淋巴减少症（RIL）对该结果的影响。虽然我们发现BRCA突变的非携带者和携带者之间的5yDFS没有显着差异（86.4％vs78.4％P=0.24），或者非携带者和其他研究突变之间的5yDFS（86.4％vs93.3％;P=0.27），分别,我们观察到,整个PV携带者组中无RIL患者的比例显著低于非携带者(P=0.04).相比之下,随后的分析表明，在具有RIL的PV载体中，5yDFS增加的趋势不显着。我们的单中心研究表明，BC患者中PV的存在对DFS的影响不大，但可以降低与辅助放疗相关的RIL风险。尚不清楚这是否可能是由于PV携带者中抗肿瘤免疫的反常激活所致，而淋巴细胞消耗较高，这是由于免疫效率较高所致。
