285P - Genomic profile of early stage node-negative luminal breast cancer associated with short disease-specific survival

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Breast Cancer, Early Stage
Translational Research
Presenter Anna Durigova
Citation Annals of Oncology (2014) 25 (suppl_4): iv85-iv109. 10.1093/annonc/mdu327
Authors A. Durigova1, P. Tsantoulis2, R. Lyle3, C. Borel4, G. Fioretta5, B. Dieterich6, P. Chappuis7
  • 1Oncology, Geneva University Hospitals, 1211 - Geneva/CH
  • 2Oncology, Geneva University Hospitals, Geneva/CH
  • 3Medical Genetics, Oslo University Hospital, Oslo/NO
  • 4Genetic Medicine And Development, University Hospitals of Geneva, Geneva/CH
  • 5Institut Of Social And Preventive Medicine, Geneva Cancer Registry, Geneva/CH
  • 6Clinical Pathology, Geneva University Hospitals, Geneva/CH
  • 7Oncology And Genetic Medicine, Geneva University Hospitals, Geneva/CH

Abstract

Aim

Prognosis of patients with estrogen receptor (ER) -positive node-negative T1-2 breast cancer is generally favorable. Even if up to 15% of patients relapse, only a minority dies shortly after diagnosis. The aim of this study was to explore the genomic features of T1-2N0 luminal breast cancer with a particularly aggressive clinical course.

Methods

We collected data from the Geneva Cancer Registry, cryopreserved tissue and extracted 12 patients with T1-2N0 ER+ grade 1-2 tumors with 4 years breast cancer specific median survival. These patients were matched with 14 control cases who had survived at least 10 years. We selected 31 genes with known impact on breast cancer prognosis and quantified their expression by qPCR. We used publicly available microarray data to validate our results in a meta-analysis. An additional gene set enrichment analysis (GSEA v2.0.13) was restricted to the groups with extremely poor and good prognosis. All P-values were adjusted.

Results

The expression of 8 genes had a significant effect on survival: ESR1 (P = 0.009), CCNE1 (P = 0.009), MKI67 (P = 0.005), BCL2 (P = 0.009), EGFR (P = 0.009), MMP9 (P = 0.021), PLAU (P = 0.009) and TIMP1 (P = 0.009). Correlations defined two groups of genes, involved in proliferation and invasion. The validation meta-analysis confirmed the prognostic value of proliferation (CCNB1 P < 10-6, CCNE1 P = 0.008, MKI67 P < 10-6, CDKN2A P = 0.04 and BIRC5 P < 10-6), but invasion-related genes were not associated with metastasis. This may be explained by the rarity of patients with very short survival. In exploratory GSEA, we identified pathways related to invasion and metabolism: embryonic stem-cell like signature (P = 0.002), gluconeogenesis (P = 0.004), glycolysis (P = 0.025), epithelio-mesenchymal transition (P = 0.072). Interestingly, several of these pathways are also involved in triple negative breast cancer.

Conclusions

Proliferation has a strong prognostic value in luminal breast cancer. Genes involved in invasion may discriminate patients with particularly aggressive disease. The co-activation of proliferation and invasion in ER+ tumors seems to promote features usually associated with triple-negative disease.

Disclosure

All authors have declared no conflicts of interest.