Clinical characteristics and cancer spectrum among breast cancer patients with TP53 germline mutation from a single institution.

Abstract

10609 Background: Li-Fraumeni syndrome (LFS), due to germline TP53 mutations, is associated with elevated risks of multiple cancers including early onset breast cancer (BC). Due to multi-disciplinary cancer screening and treatment access, The UT MD Anderson Cancer Center (MDACC) follows a large cohort of individuals diagnosed with LFS. We aimed to describe women with BC diagnosed with LFS and the spectrum of their additional cancer history before and after BC. Methods: Patients with BC and LFS were identified from a prospective BC database between 2001-2024. Patients with a pathogenic variant in TP53, and in two cases a variant of uncertain significance with special clinical consideration for LFS-management, were included for review. We evaluated the cancer histories and described the breast cancer characteristics of these women. We identified the incidence of secondary cancers post radiation therapy and secondary leukemia in patients who received alkylating agents given known secondary malignancy risks with such exposures. Summary statistics were generated for the population along with statistical methods for associations between factors of interest including, Chi-squared test and Fisher’s exact test. Results: Ninety-six women were identified with a history of BC and clinically followed for a diagnosis of LFS. A total of 127 breast tumors diagnosed among 96 women with mean age 35.8 (range 20-69 years). Of these, 68 patients had one primary BC, 26 had two BCs, one had three BCs, and one had four BCs. Individuals ranged from having a diagnosis of 1 to 7 individual cancers; 54 individuals had BC as well as at least one other type of cancer besides BC. Among individuals with more than one cancer, excluding individuals with only BCs, BC was the first cancer diagnosis in 67% (36/54). Other than BC, the other most common cancers were 40 sarcomas, 14 leukemia/other hematologic malignancy, 9 thyroid cancers, 7 brain cancers, and 29 other cancers. Fifty-six percent (54/96) of women received radiation treatment with 14 (26%) individuals developing a subsequent radiation-induced malignancy (RIM). Fourteen percent developed a hematologic malignancy following anthracycline exposure (8/56). Conclusions: This study describes the LFS population followed in a high-risk, multi-disciplinary clinic to further understand the spectrum of cancers among women with BC. Our study found that 29% of patients have at least a second BC. More than half of the patients also had a non-BC primary and, in the majority, BC was their first cancer. We also found a high rate of RIM as well as high rate of hematologic malignancies. Understanding multiple cancer histories in LFS could lead to better screening for other cancers. Summarizing the natural history of cancer frequency helps clinicians better predict when genetic testing may be warranted and aim to increase early detection of subsequent cancers.