The risk of radiotherapy-induced malignancies (RIMs) is a concern when treating Li–Fraumeni syndrome (LFS) or Li–Fraumeni Like (LFL) patients. However, the type of TP53 pathogenic germline variant may possibly influence this risk. TP53 p.R337H mutation is particularly prevalent in Brazil. We aimed to evaluate the outcomes of patients with pathogenic TP53 variants treated for localized breast cancer in a Brazilian cohort. We evaluated retrospectively a cohort of patients with germline TP53 pathogenic variants treated for localized breast cancer between December 1999 and October 2017. All patients were followed by the Hereditary Cancer Group of an academic cancer center. Our primary objective was to evaluate the occurrence of RIMs after adjuvant radiotherapy. Sixteen patients were evaluated; 10 (62.5%) had a germline TP53 p.R337H pathogenic variant. Median age was 39.8 years. Thirteen patients had invasive ductal carcinoma: 8 (61.5%) were hormone receptor-positive; 6 (46.1%), human epithelial growth factor receptor 2 (HER2)-amplified. Three patients had ductal carcinoma in situ. Most patients (N = 12/16, 75%) received adjuvant radiotherapy. After a median follow-up of 52.5 months, 2 patients (2/12, 16.6%) had RIMs. One had a fibrosarcoma and the other, a low-grade leiomyosarcoma. In the group treated with radiotherapy, one distant recurrence was diagnosed (1/12), and no loco-regional recurrence occurred. Among 4 patients who did not receive radiotherapy, 2 presented with loco-regional recurrence. In this cohort of patients with LFS enriched in TP53 p.R337H pathogenic variant, the incidence of RIMs after treatment of localized breast cancer was lower than previous literature. Nevertheless, rates of RIMs were still alarming. Early molecular diagnosis and careful evaluation of treatment risks and benefits are essential for these patients.

中文翻译：

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患有TP53致病种系变异（Li-Fraumeni综合征）的乳腺癌患者的放疗诱发的恶性肿瘤。

在治疗Li-Fraumeni综合征（LFS）或Li-Fraumeni Like（LFL）患者时，放疗引起的恶性肿瘤（RIMs）的风险是一个问题。但是，TP53致病种系变异的类型可能会影响这种风险。TP53 p.R337H突变在巴西尤为普遍。我们旨在评估在巴西队列中针对局部乳腺癌治疗的致病性TP53变异患者的结局。我们回顾性评估了TP53种系患者的队列在1999年12月至2017年10月期间针对局部乳腺癌治疗了多种致病性变体。所有患者均接受了学术癌症中心的遗传性癌症小组的随访。我们的主要目的是评估辅助放疗后RIM的发生。对16例患者进行了评估；10（62.5％）具有种系TP53p.R337H致病变异。中位年龄是39.8岁。浸润性导管癌13例：激素受体阳性8例（61.5％）；图6（46.1％），人上皮生长因子受体2（HER2）-扩增。三名患者原位导管癌。大多数患者（N = 12 / 16，75％）接受了辅助放疗。中位随访52.5个月后，有2例患者（2 / 12，16.6％）患有RIM。一个患有纤维肉瘤，另一个患有低度平滑肌肉瘤。在接受放射治疗的组中，诊断出一个远处复发（1/12），并且没有发生局部复发。在4名未接受放射治疗的患者中，有2名出现局部复发。在这个队列中，富含TP53的LFS患者p.R337H病原体变异，局部乳腺癌治疗后RIMs的发生率低于以前的文献。尽管如此，RIM的比率仍然令人担忧。对这些患者而言，早期的分子诊断以及对治疗风险和益处的仔细评估至关重要。