Abstract 25P
Background
The 27-gene HER2DX prognostic assay has been evaluated in >1300 patients (pts) with early-stage HER2+ breast cancer (BC) (EBioMedicine 2022). Here, we explored the association of the research-based HER2DX with a list of 485 genes linked to relapse-free survival (RFS) in the N9831 pivotal trial (JCO 2015).
Methods
N9831 randomized 1282 pts with early-stage HER2+ BC to adjuvant multi-agent chemotherapy (CT) (arm A), 1-year of trastuzumab starting concomitantly with CT (arm B) and 1-year of trastuzumab after CT (arm C). In JCO 2015, 485 genes were significantly (p<0.01) associated with RFS in 849 pts in arms B/C using DASL technology. Here, the primary objective was to identify available genes from the HER2DX gene list associated with RFS in arms B/C. A representation factor and the probability of finding a gene overlap were calculated. The secondary objective was to compare the expression of the N9831 485 prognostic genes in research-based HER2DX low- vs high-risk groups in 376 HER2+ BCs from METABRIC and TCGA datasets. Differentially expressed genes between both risk groups were identified (false discovery rate<5%).
Results
Five genes (CD27, CD79A, IL2RG, LAX1 and PIM2) were found in both prognostic gene lists (N9831 and HER2DX) and all belong to the HER2DX IGG signature (5 of 11 genes available; 45.5%). In N9831, the RFS hazard ratio estimate for each gene was 0.84 (CD27; p=0.002), 0.78 (CD79A; p=0.005), 0.81 (IL2RG; p=0.002), 0.85 (LAX1; p=0.008) and 0.80 (PIM2; p=0.007). The overlap between the 2 gene lists was not due to chance (enrichment factor=10.7; p<0.001). Of the genes associated with better prognosis in N9831 (n=330), 96.8% in METABRIC and 96.9% in TCGA were significantly more expressed in the research-based HER2DX low-risk group compared to the high-risk group. Of the genes associated with worse prognosis in N9831 (n=155), 66.6% in METABRIC and 35.6% in TCGA were significantly more expressed in the research-based HER2DX high-risk group compared to low-risk group.
Conclusions
The biology captured by HER2DX is significantly associated with prognostic genes found in pts treated with adjuvant trastuzumab-based CT in the N9831 trial. This result reinforces the prognostic ability of HER2DX in early-stage HER2+ BC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Brasó-Maristany: Financial Interests, Personal, Invited Speaker: Reveal Genomics. O. Martinez Saez: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche. L. Pare Brunet: Financial Interests, Personal, Full or part-time Employment: Reveal Genomics. M. Marín-Aguilera: Financial Interests, Personal, Full or part-time Employment: Reveal Genomics. P.F. Conte: Financial Interests, Personal, Expert Testimony, expert testimony for drug approval with AIFA: Roche; Financial Interests, Personal, Advisory Board, advisory board for alpelisb trial: Novartis; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: Merch Kga; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis. V. Guarneri: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Synton Biopharmaceuticals; Financial Interests, Institutional, Invited Speaker: Merck. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lilly. A. Vivancos: Financial Interests, Personal, Other, Consultant: Sysmex; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Bristol Meyers Squibb; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Other, Technology Transfer DX Field: Ferrer; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Bristol Meyers Squibb; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Novartis; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Debio; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: SYSMEX; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Cellestia Biotech; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Roche; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Chittern. J. Parker: Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Advisory Board: Reveal Genomics. P. Villagrasa Gonzalez: Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Officer: Reveal Genomics. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca; Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: Eli Lilly; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Novartis; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Gilead; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Genentech/Roche; Financial Interests, Personal, Other, Consultant: Nektar; Financial Interests, Personal, Other, Consultant: NanoString; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Eisai; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Sanofi; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Seagen; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Ad board participant/consultant/DSMC: Odonate; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Other, Consultant: Athenex; Financial Interests, Personal, Advisory Board, Ad board participant: OncoPep; Financial Interests, Personal, Advisory Board, Ad board participant: OncoSec; Financial Interests, Personal, Advisory Board, Ad board participant: Certara; Financial Interests, Personal, Advisory Board, Ad board participant: Mersana Therapeutics; Financial Interests, Personal, Advisory Board, Ad board participant: Ellipses Pharma; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: 4D Pharma; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Puma; Financial Interests, Personal, Invited Speaker, Invited speaker for pharma supported educational activity: Chugai Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory board participant: G1 Therapeutics; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board participation: OncXerna; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Seagen; Financial Interests, Institutional, Funding: Odonate; Financial Interests, Personal and Institutional, Invited Speaker: CytomX; Financial Interests, Institutional, Funding: Cyclacel; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Institutional, Funding: Gilead; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Nektar; Financial Interests, Institutional, Funding: Genentech/Roche. L.A. Carey: Financial Interests, Institutional, Funding, research funding: Syndax; Financial Interests, Institutional, Funding, research funding: Immunomedics; Financial Interests, Institutional, Funding, research funding: Novartis; Financial Interests, Institutional, Funding, research funding: NanoString Technologies; Financial Interests, Institutional, Funding, research funding: AbbVie; Financial Interests, Institutional, Funding, research funding: Seattle Genetics; Financial Interests, Institutional, Funding, research funding: Veracyte; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: sanofi; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: Novartis; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: G1 Therapeutics; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: Genentech/Roche; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: GlaxoSmithKline; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: AstraZeneca/ Daiichi Sankyo; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: Apitude Health; Non-Financial Interests, Advisory Role, uncompensated relationship - all monies go to UNC. Dr. Carey does not have any signatory authority over any UNC account: Exact Sciences. C.M. Perou: Financial Interests, Personal, Stocks/Shares: Reveal Genomics; Financial Interests, Personal, Advisory Role: Reveal Genomics; Financial Interests, Personal, Stocks/Shares: BioClassifier LLC; Financial Interests, Personal, Advisory Role: BioClassifier LLC. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Contracted research:: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Amgen; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Amgen; Financial Interests, Personal, Invited Speaker, Lecture fees: BMS; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: BMS; Financial Interests, Personal, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: NanoString; Financial Interests, Institutional, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: Novartis; Financial Interests, Institutional, Other, Contracted research: Roche; Financial Interests, Institutional, Other, Contracted research: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Contracted research; Financial Interests, Personal, Invited Speaker, Lecture fees: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Puma; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Oncolytics; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: MSD; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Guardan Health; Financial Interests, Personal, Expert Testimony, Advisory role/consultancy: Peptomyc; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Lilly; Financial Interests, Institutional, Other, Clinical trials: Lilly; Financial Interests, Institutional, Other, Contracted research: Boehringer; Financial Interests, Institutional, Other, Contracted research: Sysmex Europa GmbH; Financial Interests, Institutional, Other, Contracted research: Medica Scientia inno. Research; Financial Interests, Institutional, Other, Contracted research: Celgene; Financial Interests, Institutional, Other, Contracted research: Astellas; Financial Interests, Institutional, Other, Clinical trials: Roche; Financial Interests, Institutional, Other, Clinical trials: AMgen; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Institutional, Other, Clinical trials: Boehringer; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation. All other authors have declared no conflicts of interest.