Frequency of Radiation Therapy–Induced Malignancies in Patients With Li-Fraumeni Syndrome and Early-Stage Breast Cancer and the Influence of Radiation Therapy Technique

Abstract

IntroductionBreast cancer (BC) is the most common malignancy in female patients with Li-Fraumeni Syndrome (LFS), a condition associated with an increased risk of various malignancies, including radiotherapy-induced malignancies (RIM) within previously irradiated areas. Our study aimed to assess the incidence of RIM in LFS patients with early-stage breast cancer (eBC) treated with adjuvant radiotherapy (RT), including the impact of RT dose and technique. MethodsWe examined patients with a germline pathogenic/likely pathogenic TP53 variant diagnosed with eBC and monitored by a Hereditary Cancer Team at a single cancer center. The study endpoints included RIM frequency, the association of RIM with the dose and type of radiotherapy (2D RT, 3D RT, and IMRT), and BC recurrence. ResultsWe analyzed 48 patients with a median age of 39 years (range 21 - 62). A majority (71%) had the TP53 R337H variant, and 87% were unaware of their LFS diagnosis at the time of BC treatment. Treatment modalities included mastectomy (62%), (neo)adjuvant chemotherapy (66%), and RT (62%), with RT being more common after breast-conserving surgery (87% vs. 46% with mastectomy, P=0.010). Among the 30 patients treated with RT, 10% developed RIM in the irradiated field, consisting of three soft tissue malignancies. RT dose (≤40.8 or >40.8 Gy) did not influence RIM occurrence, but the type of RT did. RIM was observed in 100% of cases with 2D RT (2/2), 50% with IMRT (1/2), and 0% with 3D RT (0/16) (P=0.004). ConclusionOur study underscores a concerning rate of RIM following adjuvant RT, emphasizing the importance of a thorough risk-benefit evaluation before recommending RT, with preference for its avoidance if possible. Although subgroup sizes were limited, the risk of RIM appeared to be influenced by the RT technique, with higher rates observed with 2D RT and IMRT compared to 3D RT. Early TP53 testing is essential to guide the BC treatment plan.