Despite this, patients receiving chemotherapy are most frequently treated with anthracycline-taxane containing regimens, regardless of subtype. CRUK Internal Database Number 14232.īreast cancer is a heterogeneous disease, encompassing multiple molecular subtypes, some of which have targeted therapies available, including endocrine therapy and anti-HER2 therapies for oestrogen receptor-positive (ER+) and human epidermal growth factor 2 positive (HER2+) disease, respectively. Not applicable (non-interventional study). Transcriptomic data suggest induction with anthracycline-containing regimens in immune restricted, “cold” tumours may be effective for immune priming. 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. DDIR positivity correlated with immune infiltration and upregulated immune-checkpoint gene expression. Positive scores predicted response to treatment (odds ratio 4.67 for RCB 0-1 disease (95% CI 1.13–15.09, P = 0.032)).

ResultsĭDIR signature reports were available within 14 days for 97.8% of 46 patients (13 TNBC, 16 HER2 + ve, 27 ER + HER2-ve).

RNA sequencing was used to assess chemotherapy/response-related changes in biologically linked gene signatures. Baseline DDIR signature scores were correlated with pathological treatment response. 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. This feasibility study assessed the integration of a novel biomarker into clinical workflows.

This feasibility study prospectively evaluates the use of this assay to predict neoadjuvant chemotherapy response in early breast cancer.

The DNA-damage immune-response (DDIR) signature is an immune-driven gene expression signature retrospectively validated as predicting response to anthracycline-based therapy.

Ex 12.3 class 10