2025 Sequencing Strategies for Population and Cancer Epidemiology Studies (SeqSPACE) : Submission #8

Abstract Summary Tumor whole exome sequencing provides a systemic readout of the genetic architecture of the tumor. The Catalogue Of Somatic Mutations In Cancer (COSMIC) signatures capture the different underlying mutational processes that may arise from different exposures (exogenous or endogenous). We profiled tumor whole exome-sequencing among 234 triple-negative breast cancer patients from 4 U.S. based prospective cohorts (Nurses’ Health Study / NHS and NHS2 [n=151], Cancer Prevention Study /CPS II and 3 [n=83]). We compared key participant characteristics, the presence and distribution of selected tumor mutational signatures for TNBC cases identified in NHS/NHS2 and CPSII/3. Mean age at diagnosis is 59 for both NHS and NHS2 (range=36-86) and CPSII and CPS3 (range=31-85). Majority of TNBC cases had stage I or II cancers at diagnosis (90% for NHS and NHS2, 83% for CPSII and CPS3, percentage calculated from none-missing samples). For many signatures (e.g., SBS1, SBS2), we observed comparable proportions of samples with somatic mutations contributing to the signatures in NHS and NHS2 and CPSII and CPS3. As a next step, we will examine fruits and vegetable intake, dietary and circulating carotenoids, which are important sources of anti-oxidants, in relation to tumor somatic mutational patterns among TNBC cases in the 4 cohorts.