Evaluating the Impact of Presymptomatic Awareness of Clinically Actionable Breast Cancer Genes on the Clinical Stage of Breast Cancer at Diagnosis

With the growing role of genomic medicine in informing cancer care and prevention, the impact of presymptomatic awareness of genetic susceptibility on clinical outcomes is not yet well-defined. This study aims to explore the impact that presymptomatic awareness of a pathogenic or likely pathogenic (P/LP) variant in a breast cancer (BC) susceptibility gene has on the clinical stage at diagnosis. This retrospective chart review compared the BC stage at diagnosis of 202 individuals with BC from 30 different US states who also harbored P/LP variants in NCCN-designated BC risk genes. Participants were divided into two groups: those who learned about their genetic risk before a BC diagnosis (n=12) and those who learned about it after diagnosis (n=190). Due to the small number of participants who were presymptomatic at the time of testing, our study was underpowered, and no statistically significant association was observed between presymptomatic awareness and clinical stage at diagnosis. Previous studies examining presymptomatic awareness and clinical stage at diagnosis in BRCA1 and BRCA2 carriers have identified a statistically significant association, demonstrating that when statistical power is achieved, a relationship may exist. However, the small sample size, particularly in the presymptomatic group, severely limited the ability to detect statistical significance. Further expanding this research with a larger cohort and a longer follow-up period could provide deeper insights into how presymptomatic awareness influences clinical outcomes.