Abstract 260P
Background
Breast cancer is the most commonly diagnosed cancer in women worldwide, and >90% of breast cancer-related deaths are associated with metastasis. Lung and liver metastasis are of particular concern as both are associated with a high morbidity and mortality rate. A better understanding of the mechanisms that drive breast cancer lung metastasis is crucial for identifying novel biomarkers and therapeutic targets.
Methods
A total of 333 female breast cancer patients were enrolled in the study. The median age was 47 years (range, 21 to 80 years). Next-generation sequencing across 1021 genes simultaneously assessed single-nucleotide variants, insertions/deletions, rearrangements, and somatic copy-number alterations were performed on 23 lung metastasis, 40 liver metastasis, and 270 primary breast tumor samples (49 HER2 postive, 101 HR positive, and 120 triple-negative breast cancer (TNBC)).
Results
At least 1 somatic mutations were detected 329 patients (98.8%), with the median of 8 mutations (range, 0-124). The top 5 frequently mutant genes were TP53 (287, 86.1%), PIK3CA (145, 43.5%), MLL3 (50, 15.0%), GATA3 (35, 10.5%), and NF1 (33, 9.9%). Interestingly, HER2 positive and TNBC patients had a significantly higher proportion of TP53 mutations than HR positive patients (73.5% and 88.3% vs 45.5%, p<0.01), while HER2 positive and HR positive patients had a significantly higher proportion of PIK3CA mutations than TNBC patients (42.9% and 51.5% vs 21.7%, p<0.01). Notably, ATRX mutation was highly enriched in lung metastasis and liver metastasis samples compared with primary breast tumors (21.7% and 12.5% vs 4.1%, p = 0.0047 and 0.041 respectively). Of the 21 ATRX mutations identified, 6 were truncating mutations.
Conclusions
The enrichment and the loss-of-function mutation of ATRX which plays a role in telomere lengthening and stability indicated its role in promoting lung or liver metastasis, and further functional studies were warrant.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.