Dataset Information

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

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.

SUBMITTER: Parkes EE

PROVIDER: S-EPMC8770594 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Parkes Eileen E EE Savage Kienan I KI Lioe Tong T Boyd Clinton C Halliday Sophia S Walker Steven M SM Lowry Keith K Knight Laura L Buckley Niamh E NE Grogan Andrena A Logan Gemma E GE Clayton Alison A Hurwitz Jane J Kirk Stephen J SJ Xu Jiamei J Sidi Fatima Abdullahi FA Humphries Matthew P MP Bingham Victoria V James Jaqueline A JA James Colin R CR Paul Harkin D D Kennedy Richard D RD McIntosh Stuart A SA

British journal of cancer 20211102 2

<h4>Background</h4>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.<h4>Methods</h4>This feasibility study assessed the integration of a novel biomarker into clinical workflows. Tumour samples were collected from patients receiving stand ...[more]

PMID: 34728791

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Project description:BackgroundIn the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial.Patients and methodsWe analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2).ResultsA basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤ 50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2- and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤ 50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%.ConclusionBasal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis.Implications for practiceThe use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis.

Dataset Information

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

Background

Methods

Results

Conclusions

Trial registration

Publications

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

Similar Datasets

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