102P - HER2DX risk-score in early-stage HER2-positive (HER2+) breast cancer: a correlative analysis of 757 patients from the Sweden Cancerome Analysis Network - Breast (SCAN-B) dataset

Background

The HER2DX risk-score has been validated across several studies in patients (pts) with early-stage HER2+ breast cancer, including the 1st release of the SCAN-B cohort (n=378; EBioMedicine 2022). Here, we report the result of the HER2DX risk-score in the latest release of the SCAN-B HER2+ cohort, which includes a larger sample size, longer follow-up and treatment information.

Methods

The clinical and RNAseq data from the SCAN-B dataset was obtained from GEO (GSE81538). Among 6600 pts, 819 had HER2+ breast cancer and 757 pts had research-based HER2DX risk-score and survival outcomes. The HER2DX risk-score was evaluated i) as a continuous variable and ii) using predefined cut-offs. The primary endpoint for this study was overall survival (OS). The Kaplan-Meier method and Cox models were used to estimate survival outcomes.

Results

Median follow-up was 7.5 years (n=757). Most pts received chemotherapy (85.1%) and trastuzumab (79.1%), most tumours were T1-T2 (97.1%) and hormone receptor-positive (71.5%). HER2DX risk-score was associated with OS as a continuous variable (OS HR per 10-units increment=1.39, 95%CI 1.27-1.5; p<0.001) and using the predefined risk groups (cut-off=50; OS HR=2.91, 1.95-4.34; p<0.001). HER2DX risk-score remained associated with OS after adjustment by clinical variables and treatment regimen (multivariable analysis, Table). Among HER2+ T1N0 tumours (n=297), HER2DX high-risk had an inferior OS than low-risk (cut-off=50 [5.0% high-risk]; 7-years OS 68.9% vs 93.0%, p=0.02)) and using cut-off=32 ([24.6% high-risk]; 7-years OS 80.0% vs 94.9%, p=0.002). Similar results were obtained in other survival endpoints.

Table: 102P

Conclusions

In patients with early-stage HER2+ breast cancer, HER2DX risk-score provides prognostic information beyond clinical-pathological variables, including treatment regimen with or without trastuzumab.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca / Veracyte / Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech. G. Villacampa: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabrer, GSK; Financial Interests, Personal, Invited Speaker, Internal discussion about the interpretation of some published results: Pfizer; Financial Interests, Personal, Other, Collaborations with specific projects: Reveal Genomics. F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. L. Pare Brunet: Financial Interests, Institutional, Full or part-time Employment: Reveal Genomics S.L.; Financial Interests, Institutional, Other, Patent pending: In vitro method for the prognosis of patients suffering from HER2-positive breast cancer - 905333: Reveal Genomics S.L. O. Martinez Saez: Financial Interests, Personal, Invited Speaker: Novartis, Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Medical advisory: Reveal Genomics. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MERCK SHARP& DOHME, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MERCK SHARP& DOHME, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. 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