Abstract 215P
Background
Experimental studies indicate that neuroendocrine pathways impact progression in some cancers, including breast cancer. We aimed to examine whether neuroendocrine pathways are differentially mutated and expressed in tumour tissue when comparing patients with aggressive and non-aggressive breast cancer.
Methods
We conducted an extreme case-control study of 208 aggressive and 208 non-aggressive breast cancer patients who were matched on molecular subtypes and identified from the West China Hospital Breast Cancer Cohort (WCH; N=192) and The Cancer Genome Atlas (TCGA; N=224). Whole exome sequencing (WES) and RNA sequencing (RNA-seq) were performed for fresh-frozen tumour and paired normal (available in WCH) breast tissues. Neuroendocrine pathways were identified from The Kyoto Encyclopedia of Genes and Genomes (KEGG) and our previous work. We assessed differences in pathway mutation burden and expression in relation to breast cancer aggressiveness using the logistic regression and global test, respectively.
Results
Any somatic mutation of the glucocorticoid pathway was associated with the risk of aggressive breast cancer (OR 1.66, 95% CI 1.07-2.58), after adjustment for cohort membership, age at diagnosis, menopausal status at diagnosis, molecular subtype, and cancer stage. Moreover, differential expression of genes in the glucocorticoid pathway in tumour tissue was associated with the risk of aggressiveness (P = 0.028), but not in normal tissue (P = 0.701). In the glucocorticoid pathway, the strongest associations between tumour mutation burden (TMB) and individual gene expression were noted for HSP90AA1, ADCY4, SLC12A5, and GNG7 genes (P < 0.05). In addition, we observed significant associations between somatic mutation of the adrenergic and cholinergic pathways and aggressiveness in WCH, but not in TCGA, and differential expression of genes in the serotonergic pathway in tumour tissue was associated with the risk of aggressiveness (P = 0.014).
Conclusions
Our findings suggest that the glucocorticoid pathway may play a role in breast cancer prognosis through differential mutations and expression. If the function role is confirmed, it may open up avenues for developing novel therapeutic targets for breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Donghao Lu.
Funding
China Scholarship Council, Swedish Cancer Society, the Swedish Research Council for Health, Working Life and Welfare (FORTE).
Disclosure
All authors have declared no conflicts of interest.