90P - molecular feature and clinical use development of gene expression profile "TP53 signature" in early stage breast cancer

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Breast Cancer, Early Stage
Breast Cancer
Translational Research
Presenter Shigeo Yamaguchi
Citation Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363
Authors S. Yamaguchi1, S. Takahashi2, T. Nomizu3, Y. Kakugawa4, T. Ishida5, S. Kato1, C. Ishioka6
  • 1Medical Oncology, Juntendo University School of Medicine, 113-0033 - Tokyo/JP
  • 2Medical Oncology, Tohoku University Hospital, 980-8575 - Sendai/JP
  • 3Department Of Surgery, Hoshi General Hospital, Koriyama/JP
  • 4Department Of Breast Oncology, Miyagi Cancer Center Hospital, Natori/JP
  • 5Department Of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai/JP
  • 6Medical Oncology, Tohoku University Hospital, 9808675 - Sendai/JP

Abstract

Background

There have been reported many gene expression profile which can predict prognosis of early stage breast cancer. We have reported the TP53 signature which can predict dysfunction caused by TP53 gene mutation in transcriptome level, and the status defined by TP53 signature can predict more accurate prognosis of early stage breast cancer compare to the status defined by TP53 DNA sequence. Recently, TP53 signature was reported as robust predictor of early stage breast cancer by meta-analysis (BMC Cancer,2015). The aim of this study is to make clear the molecular feature of poor prognosis group diagnosed by TP53 signature and to make easy and quick diagnostic kit which can be used in clinical situation.

Methods

We have done RNA-seq analysis using Hiseq2500 (Illumina) and reanalyzed TCGA data of breast cancer to make clear molecular feature of poor prognosis group defined by TP53 signature. We made simple diagnostic kit using nCounter (Nanostring technology). Using this simple diagnostic kit, we diagnosed 234 breast cancer sample as TP53 signature mutant or TP53 signature wild, and we proved robust prediction power of TP53 signature for early stage breast cancer. We used RNA-seq data to compare prediction power of TP53 signature to Mammaprint, OncotypeDX, TP53 structural mutation.

Results

TP53 signature mutant group have structural mutation in genes, including BRCA1, BRCA2, Rb1 except for TP53, which function is gene repair. In addition, TP53 signature mutant group shows high expression of PD-L1, high mutation burden and high copy number alternation. Analysis of 190 stage I-II breast cancer patients shows TP53 signature by simple diagnostic kit using nCounter has strong prediction power compare to Mammaprint, OncotypeDX, TP53 structural mutation, and clinical factors.

Conclusions

We have developed TP53 signature as diagnostic system for early stage breast cancer which is useful in clinical situation. Poor prognosis group diagnosed by TP53 signature shows molecular features which overlap good response marker of immune-check point inhibitors.

Clinical trial identification

Legal entity responsible for the study

Japan

Funding

None

Disclosure

All authors have declared no conflicts of interest.