Abstract PO5-09-04: Oncotype DX Breast Recurrence Score® analysis in early-stage breast cancer associated with CHEK2, ATM and PALB2 germline pathogenic variants

Abstract Background: The 21-gene assay (Oncotype DX Recurrence Score, RS) is the only clinically validated assay to determine the prognosis in hormone-positive, HER2-negative breast cancer (BC) patients treated with endocrine therapy alone by predicting locoregional and distant recurrence. Outcomes of Oncotype RS in BRCA-associated BC has been studied previously, but the results of RS analysis in BC patients with the other BC susceptibility genes have not been documented. This study evaluates the clinical and pathological characteristics of BC patients with ATM, CHEK2 and PALB2 germline pathogenic variants (PV). Methods: Patients with invasive hormone-positive, HER2-negative BC who have had Oncotype DX Breast Recurrence Score® testing and who underwent genetic testing in the Breast Medical Oncology and the Breast Clinical Cancer Genetics Clinic at the University of Texas MD Anderson Cancer Center (MDACC) were identified from the prospectively maintained research database. Clinical and tumor characteristics were analyzed using descriptive statistics. Results: Between 1996 and June 2023, 5652 patients with Oncotype RS were included in this analysis. Amongst those 828 BC patients had genetic testing and 81 patients were found to have a pathogenic variant: 17 patients with a CHEK2 mutation, 10 patients with an ATM mutation, and 18 patients with a PALB2 mutation. Among patients with CHEK2 PV, median Oncotype RS was 17 (5–32) overall, 21 (13–32) for patients age 50, and 14.5 (5–28) for patients age ≥50 (p= 0.2). Among patients with ATM PV, median RS was 16.5 (3–54) overall, 25 (10–54) for patients age 50, and 14.5 (3–29) for patients age ≥50 (p= 0.19). Among patients with PALB2 PV, median RS was 26.5 (15–40) overall, 20 (15–40) for patients age 50, and 31 (26–37) for patients age ≥50 (p= 0.012). Further patient and tumor characteristics are shown in Table 1. Conclusion: This is a single-institutional cohort of hormone-positive, HER2-negative BC patients who had Oncotype RS and who underwent genetic testing. Further analysis on clinical and tumor pathological characteristics and long-term outcome is ongoing. Table1. Patient and tumor characteristics Citation Format: Fatma Akkoc Mustafayev, Angelica Gutierrez Barrera, Diane Liu, Banu Arun. Oncotype DX Breast Recurrence Score® analysis in early-stage breast cancer associated with CHEK2, ATM and PALB2 germline pathogenic variants abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-09-04.