Abstract 127P
Background
Breast neuroendocrine tumors (NETs) are a rare form of breast cancer. Some studies, with a limited number of sequenced genes and involved patients, have reported of different mutation rates in breast NET compared to IDC. The aim of this study was to investigate the comprehensive genetic landscape of breast NETs and compare it to those of IDCs and pancreatic NETs.
Methods
We collected data retrospectively on 53 patients diagnosed with breast NETs from the Oulu University Hospital and Helsinki University Hospital from January 2006 to December 2018. The diagnoses were re-reviewed to meet the latest WHO criteria of breast NETs. Their mutational profiles, mutational signatures and affected oncogenic pathways were compared with those of 724 publicly available IDC and 98 pancreatic NET cases.
Results
The only significantly different mutation rates between breast NETs and IDCs were detected in the TP53(11.3% in breast NETs and 41% in IDCs, adjusted p-value 0.027) and ADCK2 (9.4% in breast NETs vs. 0.28% in IDCs, adjusted p-value 0.045) genes. Between breast NETs and PNETs, different mutation frequencies were detected in 30 genes. For example, MEN1 was mutated in only 6% of breast NETs and 37% in PNETs (adjusted p-value 0.00050), and GATA3 mutations were found in 17.0% of breast NETs and 0% in PNETs (adjusted p-value 0.0010). The most commonly affected oncogenic pathways in the breast NET cases were PI3K/Akt/mTOR, NOTCH and RTK-RAS pathways. Breast NETs had typically clock-like mutational signatures and signatures associated with defective DNA mismatch repair in their mutational landscape. Some completely novel genetic signatures were also found, as well as previously in cancer literature unreported mutations from ADCK2 gene (in 9.4% of breast NET patients).
Conclusions
This was to date by far the largest and the most comprehensive breast NET sequencing study. It found that the breast NET mutational profile more closely resembles that of IDCs than that of PNETs. These results also revealed several potentially druggable targets, such as MMRd and PI3K/Akt/mTOR pathway, in breast NETs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The Finnish Cancer Society.
Disclosure
All authors have declared no conflicts of interest.