295P - ESR1, PGR, ERBB2, MKI67 single gene analysis in neoadjuvant-treated early breast cancer patients

Background

Currently, early breast cancer (eBC) is classified by using clinical and histopathological factors that are often considered insufficient for individualised therapy. This study is aimed at examining whether single gene mRNA expression of ESR1, PGR, ERBB2 and MKI67 can be used instead of histopathological analysis in high-risk eBC.

Methods

For this study, a sample of high-risk patients who were treated with neoadjuvant chemotherapy was selected from a prospective, multicentre cohort of 1,270 eBC patients (PiA, Prognostic Assessment in routine application, NCT 01592825). Histopathological data for ER, PgR, HER2 and Ki67 were taken from the routine results from pre-treatment core needle biopsies. Single gene mRNA expression analysis of ESR1, PGR, ERBB2 and MKI67 and intrinsic subtyping (PAM50) were generated by multiplex hybridisation method (nCounter, NanoString ®) using formalin fixed tumour material. Cut-off values were determined by ROC-analysis.

Results

A strong correlation for ESR1, PGR and ERBB2 with corresponding histopathological results (IHC/ISH) was demonstrated (Pearson’s r= 0.701, r=0.716, and r= 0.669, respectively; all p<0.001). After dichotomisation positive predictive value was 98%, 92%, and 92%, resp. Overall percent agreement was 94.5%, 92.8% and 90.8%, resp. Cohen’s Kappa showed high inter-reliability (κ=0.888, κ=0.856, κ=0.766 resp, all p<0.001). Odds ratio also indicates an association of single gene mRNA-expression with complementary histopathological and intrinsic subtypes (p<0.05). Single gene mRNA expression data of all four genes (including MKI67) was used to classify the tumours following the surrogate definitions by the St. Gallen International Expert Consensus and demonstrated concordance with histopathological groups and intrinsic subtypes.

Conclusions

Single gene mRNA expression analysis for ESR1, PGR, ERBB2 and MKI67 is feasible and, in our sample, the results show a strong correlation to the corresponding histopathological results. Single gene expression may be used as an alternative to standard histopathological analysis. In addition, also subtyping can be performed by using single gene data; however, the clinical reliability has still to be proven.

Clinical trial identification

NCT01592825 (release date: 16.12.2009).

Editorial acknowledgement

Legal entity responsible for the study

M. Vetter and E. Kantelhardt.

Funding

Wilhelm Roux Program of the Medical Faculty, Martin Luther University Halle-Wittenberg (grant number FKZ 25/36) German Federal Ministry of Education and Research (grant number: Med FKZ 031A429).

Disclosure

C. Thomssen: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, Nanostring, Onkowiisen, Pfizer, Roche, Seagen, Vifor; Financial Interests, Personal, Financially compensated role: Forum Sanitas; Non-Financial Interests, Personal, Member: AGO Breast Committee, ASCO, DGGG (Germ Soc OB/GYN), DGS (Germ Soc Senology), DKG (Germ Cancer Soc), EORTC PathoBiomarker Group; Non-Financial Interests, Personal, Member of Board of Directors: AGO -B Breast Study Group; Non-Financial Interests, Personal, Officer, representing AGO-B: BIG; Non-Financial Interests, Personal, Invited Speaker: ESO; Non-Financial Interests, Personal, Steering Committee Member: ESMO. All other authors have declared no conflicts of interest.