3MO - Association of the research-based HER2DX signatures with survival in early-stage triple-negative breast cancer (eTNBC)

Background

The HER2DX assay is prognostic in early-stage HER2-positive breast cancer by integrating tumor and nodal staging, and the expression of 3 gene signatures tracking immunoglobulin (IGG)-mediated immunity, proliferation, and luminal differentiation. Here, we assessed the prognostic value of each of the 3 HER2DX signatures in eTNBC.

Methods

Clinical and genomic data from 704 patients with eTNBC were retrieved from METABRIC (n=267), TCGA (n=118), GSE58812 (n=107), SCANB (n=126), GSE21653 (n=86). Association of IGG signature with event-free survival (EFS) was also obtained from CALGB40603 (n=443). Univariate cox regression models were used to evaluate each of the 3 signatures with relapse-free survival (RFS), EFS and overall survival (OS). Results were pooled using a random effects model to select signatures most consistently associated with survival. A new research-based HER2DX risk score with the IGG signature, tumor size (pT1 vs other) and nodal status (pN0 vs pN1 vs pN2-3) was also evaluated. Univariate cox regression models and C-statistics were used to evaluate the prognostic value of each variable.

Results

Among the 3 signatures, the 14-gene IGG signature was associated with better RFS/OS in METABRIC, better EFS in GSE21653 and CALGB40603 and better OS in SCANB (Table). The pooled analysis confirmed the association of IGG signature with RFS/EFS (HR=0.81 [95% CI 0.70-0.93], I²=18%) and OS (HR=0.80 [0.69-0.92], I²=0%). The new research-based risk score integrating tumor size, nodal status, and IGG signature (called TNBC-DX) was significantly associated with RFS/EFS and OS in all datasets (Table). TNBC-DX risk score showed higher predictive performance compared with clinical variables alone, with a C-index ranging from 0.61 to 0.80 across datasets. Table: 3MO

Conclusions

A risk score integrating tumor size, nodal staging and the IGG signature might be a valuable prognostic biomarker in eTNBC.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Brasó-Maristany, L. Paré: Financial Interests, Personal, Licensing Fees, HER2DX patent: Reveal Genomics. P.F. Conte: Financial Interests, Personal, Advisory Board: Daiichi Sankyo/Lilly, Reveal Genomics, Gilead Sciences; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech, AstraZeneca, Tesaro, BMS, Eli Lilly; Financial Interests, Institutional, Research Grant: Roche, Merck KGaA, Novartis, BMS; Financial Interests, Personal, Licensing Fees, HER2DX Patent: Reveal Genomics; Financial Interests, Personal, Expert Testimony: Roche, AstraZeneca; Financial Interests, Personal, Other, Travel Accomodations: AstraZeneca, Celgene, Novartis, Pfizer. A. Vivancos: Financial Interests, Personal, Stocks/Shares: Reveal Genomics. P. Villagrasa Gonzalez: Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Advisory Board: Reveal Genomics; Financial Interests, Personal, Licensing Fees, HER2DX patent: Reveal Genomics. J. Parker: Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Advisory Board: Reveal Genomics. C.M. Perou: Financial Interests, Personal, Stocks/Shares: Reveal Genomics, BioClassifier LLC; Financial Interests, Personal, Advisory Board: Reveal Genomics. A. Prat: Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Advisory Board: Reveal Genomics; Financial Interests, Personal, Licensing Fees, HER2DX patent: Reveal Genomics; Financial Interests, Personal and Institutional, Other, Grants and Personal Fee: Daiichi Sankyo Roche AstraZeneca Foundation Medicine Oncolytics Biotech Novartis. All other authors have declared no conflicts of interest.