158P - In silico analysis of HER2 enriched subtype and a HER2 index based on transcriptomic data of breast cancer compared to gastric and uterine serous carcinomas

Background

In Breast cancer (BC) PAM50 platform has identified a HER2-enriched (HER2E) subgroup with predictive and prognosis implications. Our study aimed to perform an in-silico analysis to confirm the prognostic role and the association of two genomic signatures (HER2E and HER2index) with the HER2 expression in gastric (GC) and Uterine serous carcinoma (USC) in comparison to BC.

Methods

We extracted clinical, transcriptomic, and proteome data of primary tumors from 3 publicly available databases: 1) TCGA-BRCA of BC (n=1095), 2) TCGA-STAD of GC (n=412), and 3) TCGA-UCEC (serous subtype) of USC (n=138). Patients were classified according to the PAM50 definition of breast cancer. Moreover, we calculated the correlation of the tumor expression profiles with the HER2 index signature (Li et al 2020 ). The association of the HER2-related, expression-based biomarkers with overall survival was calculated with independent Cox Proportional Hazard models, separately for each TCGA cohort.

Results

In the BC dataset, HER2E subtype was positively correlated with HER2mRNA and HER2protein (HER2p) (p<0.001 ) with a trend towards a correlation with HER2phospoprotein (pp). HER2 index in BC was correlated with HER2pp (p<0.001) and non-signifcantly with HER2mRNA (p=0.069), and HER2p (p=0.087). Both HER2E and HER2index showed an impaired survival in BC (p=0.032 and p=0.002 respectively). In GC cohort, no correlation was found between HER2E and HER2mRNA. HER2 index was correlated only with HER2mRNA (p<0.001). HER2E and HER2 index were not associated with survival. For the USC cohort, HER2E and HER2index were not correlated with HER2mRNA, HER2p, or HER2p, although HER2E showed a trend towards a positive association with HER2mRNA and HER2p (p=0.059 and 0.053 respectively). These signatures were not prognostic in terms of PFS in the USC cohort (HER2E p=0.284 and HER2 index p=0.771).

Conclusions

HER2E subtype of PAM50 and HER2 index signatures showed significant correlations with HER2 expression and survival in BC, however when these signatures were applied to other HER2 tumors such as GC or USC the prognostic role and correlation with the HER2 protein expression is limited.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

INCLIVA.

Funding

Has not received any funding.

Disclosure

T.C. Fleitas: Financial Interests, Personal, Invited Speaker, Update on the ongoing treatment strategies for GEA: Servier; Financial Interests, Personal, Invited Speaker, The clinical impact of NRTK strategies in GI tumors: Bayer; Financial Interests, Personal, Invited Speaker, Invited as a speaker in an educational session.: Bristol, Amgen; Financial Interests, Personal, Invited Speaker, Invited speaker in an educational session: Bristol, MSD, Lilly, Roche; Non-Financial Interests, Principal Investigator, PI of SURPASS-2 study: Adapt Immune; Non-Financial Interests, Principal Investigator, PI of a clinical trial in GEA tumors: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, PI of a clinical trial: BeiGene. J.A. Perez Fidalgo: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, GSK, PharmaMar, Eisai, Clovis; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, PharmaMar; Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, PharmaMar. All other authors have declared no conflicts of interest.