Abstract P5-09-02: Clinical and pathological characteristics and screening outcome for secondary cancers of women with breast cancer and Li-Fraumeni syndrome
Authors: Al-Awadhi A , Liu DD , Gutierrez-Barrera AM , Strong LC , Arun BK 
Published: May 2019

Background: Germline TP53 mutations predispose to early onset breast cancer in women and are associated with Li-Fraumeni syndrome. Published data on the clinical and pathological characteristics and screening outcome for secondary cancers among women with breast cancer and TP53 mutations is limited. To the best of our knowledge this is the largest cohort of breast cancer associated with Li-Fraumeni syndrome.

Methods: Patients with breast cancer and Li-Fraumeni Syndrome were identified from a prospective research database from 2001 to 2017. Patients had genetic counselling and testing at The University of Texas MD Anderson Cancer Center and confirmed to have TP53 mutations associated with Li-Fraumeni syndrome. We reviewed the patient's charts to identify the clinical and pathological characteristics of their breast cancer. Data for secondary cancers are obtained only for patients with breast cancer as their initial cancer diagnosis and who are followed at The MD Anderson's Li-Fraumeni Education and Early Detection (LEAD) clinic which conducts comprehensive cancer screening for these patient's per the NCCN guidelines, including yearly whole body MRIs.

Results: Fifty-nine patients confirmed to have Li-Fraumeni syndrome and breast cancer (100% female, median age 30 years). 94% of the patients were pre-menopausal at the time of breast cancer diagnosis and 6% were post-menopausal due to bilateral salpingo-oophorectomy. 61% were diagnosed after abnormal self or clinical breast exam and 26% based on abnormal screening mammography or ultrasound. In terms of the histologic subtype of breast cancer: 69% had invasive ductal carcinoma, 5% mucinous carcinoma, 5% mixed ductal and lobular, 5% sarcoma, 3% phylloides tumor and 13% with missing data. Pathologic stage per the 7th edition of AJCC cancer staging system was as follows: 23% stage I, 26% stage II, 23% stage III, 28% remaining with unknown pathologic stage. Pathologic markers include: 70% with positive estrogen receptor expression, 64% with positive progesterone receptor expression, 57% with HER-2 amplification defined per the ASCO-CAP HER-2 test guidelines and 7% with triple negative disease. Forty three patients were followed at LEAD clinic. Of the 43 patients, 40% (N=17) were diagnosed with 1 primary cancer other than breast cancer, 7% (N=7) with 2 primary cancers other than breast cancer and 44% (N=19) with breast cancer only. Out of the 43 patients, 5 were diagnosed with acute myelogenous leukemia, 4 with leiomyosarcoma, 3 osteosarcoma, 4 with other types of sarcoma, 4 with central nervous cell tumors (astrocytoma or glioblastoma multiforme), 3 with papillary thyroid carcinoma, 1 with pancreatic cancer, 1 with renal cell carcinoma, 1 adrenocortical carcinoma, 1 with uterine cancer, 1 with melanoma and 1 with cervical cancer.

Conclusion: This study to our knowledge is the largest cohort of patient's with Li-Fraumeni syndrome and associated breast cancer that is followed in a dedicated clinic for patients with Li Fraumeni Syndrome. This cohort highlights the characteristics of patients with Li-Fraumeni syndrome and associated diagnosis of breast cancer as well as other primary cancers.

Citation Format: Al-Awadhi A, Liu DD, Gutierrez-Barrera AM, Strong LC, Arun BK. Clinical and pathological characteristics and screening outcome for secondary cancers of women with breast cancer and Li-Fraumeni syndrome [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-02.