Fol. Biol. 2023, 69, 91-98
Radiation-Induced Lymphopoenia and Treatment Outcome in Hereditary Breast Cancer Patients
Many breast cancer (BC) predisposition genes encode proteins involved in DNA damage repair (DDR). Identification of germline pathogenic variants (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.
Keywords
breast cancer, adjuvant radiotherapy, radiation-induced toxicity, multigene panel testing, hereditary cancer predisposition, germline pathogenic variant, BRCA1, BRCA2, ATM, PALB2, RAD51C, RAD51D.
Funding
This study was supported by the Ministry of Health of the Czech Republic (MH CZ-DRO, General University Hospital in Prague – VFN, 00064165 and NU20-03-00283), by institutional funding of Charles University (COOPERATIO, Oncology and Haematology), and by National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) funded by the European Union – Next Generation EU (LV).
