Abstract PS8-04: Clinical and pathological characteristics and screening outcome for secondary cancers in breast cancer patients with li-fraumeni syndrome attending the MD anderson li-fraumeni education and early detection program clinic
Authors: Al-Awadhi Aydah , Abuhadra Nour , Liu Diane D , Barrera Angelica M Gutierrez , Corredor Jessica , Strong Louise C , Arun Banu K 
Published: February 2021

Background: Germline TP53 mutations predispose to early onset breast cancer (BC) and are associated with Li-Fraumeni syndrome (LFS) Published data on the clinical and pathological characteristics and screening outcome for secondary cancers among women with BC and TP53 mutations is limited. The UTMD Anderson's Li-Fraumeni Education and Early Detection (LEAD) program conducts comprehensive cancer screening for patients with LFS. Here we report characteristics and screening outcome of patients with BC and LFS who were referred to the LEAD program.

Methods: Patients with BC and LFS were identified from a prospective BC database between 2001 to 2018. Patients had genetic testing at The University of Texas MD Anderson Cancer Center (MDACC) Clinical Cancer Genetics (CCG) program and confirmed to have germline TP53 mutations. Data reviewed included clinical and pathological characteristics of their BC, the pattern of referral to the LEAD program, adherence to screening recommendation and rate of secondary cancer detection in the LEAD program.

Results: A total of 78 female patients with positive germline TP53 mutation and BC diagnosis were identified. The clinical and pathological characteristics of these patients are provided in table 1. Out of the 78 patients, 62 patients were referred and followed at the LEAD clinic. 50 were referred after BC diagnosis and 12 were referred to LEAD clinic before BC diagnosis. A total of 137 cancers were diagnosed in the total population. The cancers were further grouped into diagnosed before or after BC diagnosis. (table 2). 24 cancers were diagnosed in LEAD clinic including 12 breast cancers, 2 soft tissue tumors, 2 thyroid cancers, 2 acute myeloid leukemia, 1 brain tumor, 1 lung cancer, 1 pancreatic cancer, 1 melanoma, 1 parotid cancer and 1 Merkel cell cancer. Adherence to follow up and recommended screening in the first year was 77%, second year 75% and third year 65%. 6 patients, who were diagnosed with leukemia, had received adjuvant chemotherapy with anthracycline and/or cyclophosphamide-based therapy for breast cancer with median time from chemotherapy to leukemia diagnosis of 9 years (5-10yrs). 8 patients developed chest wall sarcoma in the same location of prior radiation therapy for breast cancer with median time from radiation therapy to chest wall sarcoma diagnosis of 7 years (3-11yrs).

Conclusion: Patients with LFS associated breast cancer are at significant increased risk to develop secondary cancers. Increased surveillance for secondary cancers in a dedicated program can increase adherence to screening, lead to early detection that could potentially lead to improved outcomes. Patient outcome of this cohort will be presented at the meeting.

Table 1: Clinical and Pathological Characteristics of Women with Breast cancer and LFSN(%)N(%)Median Age (Range)33 (20, 63)——Hormonal receptor/HER-2 status+/+22(31.4%)RaceAsian/Pacific islander7(9%)+/-27(38.6%)Black8(10.3%)-/+14(20%)Hispanic12(15.4%)-/-7(10%)White51(65.4%)Menopausal status at the time of BC diagnosis.Pre-menopausal(72%)Stage013(16.9%)Post-menopausal(28%)I21(27.3%)HistologyDCIS12(15.6%)II31(40.3%)IDC49(63.6%)III9(11.7%)ILC3(3.9%)IV3(3.9%)LCIS1(1.3%)Breast cancer diagnosisMRI4(5.2%)Mixed8(10.4%)Palpated lesion51(66.2%)Mucinous2(2.6%)Screening mammogram22(28.6%)Phyllodes2(2.6%)

Table 2: Cancer diagnosed in the total population N=78 grouped into before and after to BC diagnosisCancer diagnosed before BC diagnosisNCancer diagnosed after BC diagnosisNSoft tissue sarcoma13Soft tissue sarcoma18CNS1Lung2Thyroid3Thyroid3leukemia2Merkel cell1Adrenal2Leukemia6Uterus1CNS3Renal1pancreas1Melanoma1Parotid1

Citation Format: Aydah Al-Awadhi, Nour Abuhadra, Diane D Liu, Angelica M Gutierrez Barrera, Jessica Corredor, Louise C Strong, Banu K Arun. Clinical and pathological characteristics and screening outcome for secondary cancers in breast cancer patients with li-fraumeni syndrome attending the MD anderson li-fraumeni education and early detection program clinic [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 PS8-04.