Abstract PS16-34: Phenotype and prognosis of patients with breast cancer and pathogenic TP53 variants

Abstract

Abstract Background: The lifetime risk of cancer in individuals with Li Fraumeni syndrome (LFS) is more than 70% for men and more than 90% for women. Breast cancer (BC) is the most common type of cancer in premenopause women with pathogenic allelic TP53 variants (PVs). However, little is known about the BC response to systemic therapy and the prognosis in these patients. We aim to analyze the phenotype and the outcomes of patients with LFS and BC. Methods: We evaluated a cohort of patients with PVs or likely PVs of TP53 with BC diagnosis treated from December 1999 to June 2020 from a single tertiary cancer center. Our primary objective is to evaluate the outcomes of these patients. Secondary objective is to describe the BC phenotype, characterizing the clinical and the pathological features.Results: Among 56 patients with PVs or likely PVs of TP53, 25 were diagnosed with BC. Median age at BC diagnosis was 39.2 years (range 23.4-57.4 years). The majority (N= 18, 72%) harbored a germline PV TP53 p.R337H in heterozygosity status. The most common histology type was an invasive carcinoma of no special subtype, 73% were hormone receptor-positive, and 32% were HER2-positive. Three (12%) patients were metastatic at diagnosis. Seven (28%) of the patients with localized disease at diagnosis received neoadjuvant chemotherapy, and other 7 (28%) received adjuvant chemotherapy. Among patients treated with neoadjuvant chemotherapy, 5 (71%) had a tumor response, while 2 (29%) presented with disease progression. No pathologic complete response was achieved. After a median follow-up of 52.6 months, no deaths secondary to breast cancer occurred. Only 1 patient died due to another neoplasm (jaw osteosarcoma), and 3 (12%) patients developed radiotherapy-induced malignancies in the irradiated field. Conclusions: BC in patients with LFS is mainly the invasive carcinoma of no special subtype, enriched in hormone receptor and HER2 positivity. Although response to neoadjuvant chemotherapy is high, no pathologic complete response occurred in this cohort. Favorable outcomes were observed, with a high BC specific survival. Secondary malignancies remain a major concern. Larger cohorts should test whether new genes act as modifiers of p53 function and breast cancer susceptibility. Citation Format: Vanessa Petry. Phenotype and prognosis of patients with breast cancer and pathogenic TP53 variants [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-34.