Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer.
Br J Cancer
; 126(2): 247-258, 2022 02.
Article
in En
| MEDLINE
| ID: mdl-34728791
ABSTRACT
BACKGROUND:
The 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.METHODS:
This 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.RESULTS:
DDIR 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.CONCLUSIONS:
This 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 REGISTRATION Not applicable (non-interventional study). CRUK Internal Database Number 14232.
Full text:
1
Database:
MEDLINE
Main subject:
DNA Damage
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Breast Neoplasms
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Bridged-Ring Compounds
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Neoadjuvant Therapy
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Taxoids
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Membrane Proteins
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Neoplasm Recurrence, Local
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Nucleotidyltransferases
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
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Female
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Humans
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Middle aged
Language:
En
Year:
2022
Type:
Article