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BackgroundThe DNA-damage immune-response (DDIR) signature is an immune-driven gene expression signature retrospectively validated as predicting response to anthracycline-based therapy. This feasibility study prospectively evaluates the use of this assay to predict neoadjuvant chemotherapy response in early breast cancer.MethodsThis feasibility study assessed the integration of a novel biomarker into clinical workflows. Tumour samples were collected from patients receiving standard of care neoadjuvant chemotherapy (FEC + /-taxane and anti-HER2 therapy as appropriate) at baseline, mid- and post-chemotherapy. Baseline DDIR signature scores were correlated with pathological treatment response. RNA sequencing was used to assess chemotherapy/response-related changes in biologically linked gene signatures.ResultsDDIR signature reports were available within 14 days for 97.8% of 46 patients (13 TNBC, 16 HER2 + ve, 27 ER + HER2-ve). Positive scores predicted response to treatment (odds ratio 4.67 for RCB 0-1 disease (95% CI 1.13-15.09, P = 0.032)). DDIR positivity correlated with immune infiltration and upregulated immune-checkpoint gene expression.ConclusionsThis study validates the DDIR signature as predictive of response to neoadjuvant chemotherapy which can be integrated into clinical workflows, potentially identifying a subgroup with high sensitivity to anthracycline chemotherapy. Transcriptomic data suggest induction with anthracycline-containing regimens in immune restricted, "cold" tumours may be effective for immune priming.Trial registrationNot applicable (non-interventional study). CRUK Internal Database Number 14232.

Original publication

DOI

10.1038/s41416-021-01599-0

Type

Journal article

Journal

British journal of cancer

Publication Date

02/2022

Volume

126

Pages

247 - 258

Addresses

Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, UK.

Keywords

Neo-DDIR Investigators, Humans, Breast Neoplasms, Neoplasm Recurrence, Local, DNA Damage, Taxoids, Nucleotidyltransferases, Membrane Proteins, Antineoplastic Agents, Treatment Outcome, Neoadjuvant Therapy, Gene Expression Regulation, Neoplastic, Adult, Middle Aged, Female, Biomarkers, Tumor, Bridged-Ring Compounds