Abstract 298P
Background
The remarkable advances in next generation sequencing have revolutionized precision medicine. Here we studied clinical and genomic characteristics of relapsed breast cancer (BC) patients.
Methods
Targeted sequencing of 425 cancer-relevant genes was applied to baseline tumor samples(n=39) and plasma samples(n=42) including 29 with longitudinal plasma samples. Variants were considered as clonal hematopoiesis (CH) mutations if plasma VAF more than two folds higher than that in tumor tissue.
Results
A total of 42 treatment-refractory BC patients were enrolled with a median age of 52 years old. There were 14 stage I-II, 23 stage III, and 5 stage IV BC patients. Histologic subtypes included 21 luminal (HER2-), 4 luminal (HER2+), 8 HER2+ and 9 triple-negative breast cancer (TNBC). The most frequently mutated genes in the tumor tissues were TP53(21/39, 54%) and PIK3CA (13/39, 33%). Homologous recombinant repair pathway-associated genes were altered in 17 patients. Patients with altered TP53 displayed shorter overall survival (OS) than wild-type TP53 (hazard ratio = 3.39, 95% CI = 1.09-10.48, P =0.02). TNBC were found to be associated with significantly shorter disease-free survival (DFS) than other subtypes, while invasive carcinomas of no special type (NST, n=15) were associated with poor OS (p<0.05) compared to non-NST patients. CH variants were identified in six patients (6/29, 21%) with serial plasma samples and DNMT3A (5/6, 83%) was the most frequently observed gene. Other CH variants included KDR, RECOL4, ZNF217 and TET2 alterations. BC patients with CH variants displayed longer OS than patients without.
Conclusions
Comprehensive genomic profiling revealed prognosis-relevant alterations in treatment-refractory breast cancer patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The Second Affiliated Hospital of Dalian Medical University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.