E. Ortolan (MILANO, Italy)
Fondazione IRCCS Istituto Nazionale dei TumoriAuthor Of 1 Presentation
12P - The RODILIA pilot study for molecular screening of patients with metaplastic breast cancer
Abstract
Background
Metaplastic breast cancer (MPBC) is a rare disease characterized by aggressive features and dismal prognosis after standard therapy. Herein, we report the molecular screening of the Milan National Cancer Institute case series for the evaluation of potentially druggable alterations.
Methods
A total of 49 MPBC cases treated with curative intent were identified. Primary tumors were profiled using Oncomine Comprehensive Assay Plus panel (Thermo Fisher Scientific) for copy number alteration (CNA), mutation, tumor mutational burden (TMB), and microsatellite instability (MSI) analyses, according to the manufacturer instructions.
Results
Sequencing results are presented for the first 34 pathological reviewed cases. Quality control metrics were met in 33 cases. In total, 94 unique genes harbored at least one mutation representing 24% of the panel. The median number of mutations indexed per patient was 3.5 (range 0-29). Notably, 25 cases showed actionable mutated genes, including PTEN, mTOR, FGFR3, FGFR4. Most of the cases showed low TMB, the median value being 4.5 (range 0-28). MSI status was high only in 2 cases. Common CNAs included 13q (10%), 5q (9%) and 17p (6%). Eight out of ten canonical cancer pathways (cell cycle, Hippo, MYC, NOTCH, PI3K, RTK-RAS, TGFβ and β-catenin/WNT) were altered by both mutational and CNA events occurring at different proportions, with mutational events involving up to 33%, and CNA involving up to 42% of genes of the altered pathway. In the Hippo and RTK-RAS pathways the two types of alterations were instead equally represented whereas the remaining pathways (β-catenin/WNT, TGFβ, PI3K, NOTCH, MYC and Cell cycle) were more affected by CNA than mutations. NRF2 and TP53 signaling pathways were instead activated by mutational events only.
Conclusions
Mutational and copy number alterations conveyed complementary information in MPBC cooperating in activation of cancer pathways.These findings suggest to further study the value of CNAs in MPBC biological processes, especially immunogenicity, which cannot be explained by the low TMB and MSI found. Extended data with matched immune profile will be presented at the meeting.
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
Funding
Italian Ministry of Health.
Disclosure
All authors have declared no conflicts of interest.