Abstract P4-12-33: Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome

Abstract

Abstract Background. Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer (BC) by age 70. Providers often avoid adjuvant radiotherapy to treat BC in LFS patients due to a reported high risk of radiation-induced malignancies of over 30%. We aimed to investigate the characteristics of LFS-associated BC and the risk of subsequent malignancy in BC patients with LFS following adjuvant radiotherapy. Methods. A single institution retrospective chart review was conducted for female BC patients with a confirmed germline TP53 mutation. Statistical analyses were performed to compare the frequency of radiation-induced malignancies in LFS patients to non-LFS BC cases reported in the Penn Medicine Cancer Registry (PMCR) (n=6607 patients total, 3863 who received radiation). Results. Among 95 patients with LFS, we identified 51 female BC patients with 74 primary BC diagnoses. Of 51 patients, 57% had a history of BC only, and 25% had BC as their presenting diagnosis of LFS. LFS-associated BCs were predominantly invasive ductal carcinoma (48%) and HER2+ (58%). We analyzed 20 LFS BC patients who underwent adjuvant radiotherapy with an average follow up of 11.1 (2-20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer and one (6%) patient developed sarcoma in the radiation field. The incidence of thyroid cancer did not significantly differ between LFS-associated and non-LFS BCs. The incidence of radiation-induced sarcoma in patients with LFS is significantly higher than in non-LFS BC patients (0.03%, p=0.01). Conclusion. We found a 6% (one in 18 patients) risk of radiation-induced sarcoma in LFS BC patients, lower than the previously reported rate of 33%. Adjuvant radiotherapy should be considered in LFS BC patients when the potential risk for locoregional recurrence (LRR) or the mortality benefit to radiation is greater than 6%. Citation Format: Anh N Le, Jacquelyn Powers, Kristin Zelley, Angela Bradbury, Payal Shah, Gary Freedman, Katherine Nathanson, Susan M Domchek, Suzanne P MacFarland, Kara N Maxwell. Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-33.