Details

Autor(en) / Beteiligte

• Parkes, Eileen E
• Savage, Kienan I
• Lioe, Tong
• Boyd, Clinton
• Halliday, Sophia
• Walker, Steven M
• Lowry, Keith
• Knight, Laura
• Buckley, Niamh E
• Grogan, Andrena
• Logan, Gemma E
• Clayton, Alison
• Hurwitz, Jane
• Kirk, Stephen J
• Xu, Jiamei
• Sidi, Fatima Abdullahi
• Humphries, Matthew P
• Bingham, Victoria
• James, Jaqueline A
• James, Colin R
• Paul Harkin, D
• Kennedy, Richard D
• McIntosh, Stuart A

Titel

Activation of a cGAS-STING-mediated immune response predicts response to neoadjuvant chemotherapy in early breast cancer

Ist Teil von

• British journal of cancer, 2022-02, Vol.126 (2), p.247-258

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2022

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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. 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. 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. 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. Not applicable (non-interventional study). CRUK Internal Database Number 14232.