Abstract 298P
Background
Cutaneous metastasis (CM) is the result of lymphatic embolization, hematogenous or contiguous dissemination and are present in around 24% of patients with metastatic breast cancer (BC). CM is related with very poor prognosis. To know genes involved in the development of CM is important to gain insights into the biology of the disease and to identify possible diagnostic and therapeutic biomarkers. The objective of this study is to compare the mutational profile of primary breast carcinomas and their metastases to identify genes involved in the cutaneous metastatic process.
Methods
Patients with CM were identified through the database, and samples of primary tumor and metastasis tissue were collected. A sequencing panel including the 60 most frequently mutated genes in breast cancer and 8 commonly amplified regions was designed using the SureSelect kit from Agilent. Sequencing data were analyzed using the version of the public genome hg38 versus Ensembl version 88 to include relevant information. We made a functional annotation of the genomic variants that were detected using different public databases, such as COSMIC, 1000 Genomes, Ensemble, NCBI or CIBERER Spanish Variant Server. Finally, we filtered according to different criteria.
Results
Thirty samples from 15 paired cases (primary tumor and metastasis) were sequenced. There were 10 estrogen receptor (ER) positive BCs and 5 triple negative (TN) BCs. The most frequently mutated genes in primary tumors and metastases were PIK3CA (6 ER-positive) and TP53 (4 TN BCs). De novo mutation in TP53 (not present in the primary tumor) occurred in 1 ER-positive BC and 1 TN BC. In addition to some mutations of unknown significance, pathogenic mutations in KRAS (1 tumor) and CDH1 (E-Cadherin) (1 tumor) occurred in 2 ER-positive metastatic BCs.
Conclusions
Although the mutational pattern was similar in primary BCs and their CM, up to 25% of BC in our series showed additional pathogenic mutations in key tumor suppressor genes or oncogenes in CM. Whereas no new PIK3CA mutations were observed in skin metastases, TP53 was detected only in metastases in 13% of the patients, indicating its potential role in tumor progression. Other genes involved in tumor progression in this series included KRAS and CDH1.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Instituto de Salud Carlos III (CIBERONC).
Disclosure
All authors have declared no conflicts of interest.