303P - Differential prognostic role of PDGFRA alterations in breast cancer subtypes

Background

The platelet – derived growth factor (PDGF) signaling pathway and its main representative, PDGF receptor alpha is reportedly expressed in early breast cancer and has been associated with aggressive tumor features and worse outcomes. The aim of this study was to examine the prognostic relevance of PDGFRA molecular alterations across different breast cancer subtypes.

Methods

Patients with a diagnosis of non-metastatic, invasive breast carcinoma from The Cancer Genome Atlas (TCGA), including estrogen receptor (ER)-positive (n=594), ER-negative (n=174), human epidermal growth factor receptor 2 (HER2)-positive (n=120), and triple-negative (n=82) cohorts were interrogated for presence of somatic molecular alterations in PDGFRA gene. Kaplan Meier survival analysis was used to determine the associations between altered PDGFRA and disease-free survival (DFS).

Results

Sixty patients (10%) from the ER-positive cohort had altered PDGFRA, including 2 patients with gene amplification, 3 with missense mutations, 1 with homologous deletion and 55 with elevated mRNA expression. These patients had a longer DFS compared to those with unaltered PDGFRA (not reached vs 168 months, log-rank p=0.04). In the ER-negative cohort, 24 patients (14%) had tumors harboring PDGFRA alterations including 5 amplifications, 2 missense and 1 nonsense mutation, and high mRNA (n=16). There was a trend towards a shorter DFS in these patients (p=0.23). Within the HER2-positive cohort, 11 patients (9%) had somatic gene amplifications (n=1), missense mutation (n=1), and elevated mRNA (n=9). These patients experienced a significantly worse DFS (56 months vs not reached, p<0.001). Among TNBC patients, 10 (12%) were characterized by PDGFRA amplification (n=2), missense (n=2) and nonsense (n=1) mutations, and high mRNA (n=5). This group also featured a non-significant trend towards worse DFS (p=0.39).

Conclusions

PDGFRA molecular alterations in early breast cancer are mainly characterized by amplification and increased transcript levels. Their prognostic utility is variable depending on the hormone receptor- and HER2-status. An intriguing association with favorable prognosis in ER-positive cohort was found that merits further investigation.

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.