Abstract LB391: Pre-diagnostic exposures, mutational signatures, and immune profiles in triple-negative breast cancer: An overview of the PREMISE-TN project

作者：Deborah A. Tadesse, Clara Bodelon, Cheng Peng, Kristen D. Brantley, Margaux Delporte, Yujing J. Heng, Lauren R. Teras, Rulla M. Tamimi, Peter Kraft · 发表于：Cancer Research · 年份：2026 · DOI：10.1158/1538-7445.am2026-lb391 · 研究领域：Cancer Genomics and Diagnostics、Cancer Immunotherapy and Biomarkers、Breast Cancer Treatment Studies

Abstract Triple negative breast cancer (TNBC) exhibits distinct evolutionary pathways reflected in heterogeneous mutational and immune profiles. To better understand the relationships between prediagnostic exposures, inherited genetic variation, mutational and immune profiles in TNBCs, the PRediagnostic Exposures, Mutations, Immune SignaturEs-Triple Negative (PREMISE-TN) project performed whole exome sequencing (WES) of matched formalin-fixed paraffin embedded tumor tissue and germline DNA samples from 322 TNBC patients from four prospective cohort studies, the Nurses’ Health Study (NHS, NHS II) and the Cancer Prevention Study (CPS II, CPS3). After excluding 66 mis-matched tumor normal-pairs and 32 pairs where either the tumor or blood sample did not reach the target coverage (70% of bases covered at 20x), 224 pairs were available for analysis. The median sequencing depth for tumor samples in these pairs was 111.2x (range=7.4x-481x); the median for blood samples was 283.4x (range=156.2x-652.1x). Mutational calling and sequencing quality assessment and control is underway. Patients’ age at diagnosis ranged from 34-86 years (median=58), and year of diagnosis ranged from 1976-2018 (median=2004). 56 (28.7%) of the patients were premenopausal at diagnosis. Most tumors (n=162, 88.5%) were stage I-II; 19 (10.3%) were stage III and 1 (0.5%) was stage IV. PREMISE-TN integrated somatic mutational profiles with other data from these cohorts, including: germline genome-wide association s...