Evidence map›Paper›PMID 34465315›Full record

ArticleBMC medicine2021

Combined homologous recombination repair deficiency and immune activation analysis for predicting intensified responses of anthracycline, cyclophosphamide and taxane chemotherapy in triple-negative breast cancer.

Gaoming Liao, Zedong Jiang, Yiran Yang, Cong Zhang, Meiting Jiang, Jiali Zhu, Liwen Xu, Aimin Xie, Min Yan, Yunpeng Zhang and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
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  11. RNA-Based Classification of Homologous Recombination Deficiency in Racially Diverse Patients with Breast Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Gaoming Liao *College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
Zedong Jiang *College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
Yiran Yang *College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
Cong ZhangDepartment of Ultrasonic Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin, 150010, Heilongjiang, China.
Meiting JiangKey Laboratory of University in Heilongjiang Province, Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.
Jiali ZhuCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
Liwen XuCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
Aimin XieCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
Min YanCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China.
Yunpeng ZhangCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China. zhangyp@hrbmu.edu.cn.
Yun XiaoCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China. xiaoyun@ems.hrbmu.edu.cn.
Xia LiCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang, China. lixia@hrbmu.edu.cn.
Harbin Medical University · CNFirst Affiliated Hospital of Harbin Medical University · CNSecond Affiliated Hospital of Harbin Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTriple-negative breast cancer (TNBC) is a clinically aggressive disease with abundant variants that cause homologous recombination repair deficiency (HRD). Whether TNBC patients with HRD are sensitive to anthracycline, cyclophosphamide and taxane (ACT), and whether the combination of HRD and tumour immunity can improve the recognition of ACT responders are still unknown.

methodsData from 83 TNBC patients in The Cancer Genome Atlas (TCGA) was used as a discovery cohort to analyse the association between HRD and ACT chemotherapy benefits. The combined effects of HRD and immune activation on ACT chemotherapy were explored at both the genome and the transcriptome levels. Independent cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO) were adopted to validate our findings.

resultsHRD was associated with a longer ACT chemotherapy failure-free interval (FFI) with a hazard ratio of 0.16 (P = 0.004) and improved patient prognosis (P = 0.0063). By analysing both HRD status and ACT response, we identified patients with a distinct TNBC subtype (ACT-S&HR-P) that showed higher tumour lymphocyte infiltration, IFN-γ activity and NK cell levels. Patients with ACT-S&HR-P had significantly elevated immune inhibitor levels and presented immune activation associated with the increased activities of both innate immune cells and adaptive immune cells, which suggested treatment with immune checkpoint blockade as an option for this subtype. Our analysis revealed that the combination of HRD and immune activation enhanced the efficiency of identifying responders to ACT chemotherapy (AUC = 0.91, P = 1.06e-04) and synergistically contributed to the clinical benefits of TNBC patients. A transcriptional HRD signature of ACT response-related prognostic factors was identified and independently validated to be significantly associated with improved survival in the GEO cohort (P = 0.0038) and the METABRIC dataset (P < 0.0001).

conclusionsThese findings highlight that HR deficiency prolongs FFI and predicts intensified responses in TNBC patients by combining HRD and immune activation, which provides a molecular basis for identifying ACT responders.

Indexed as

Triple Negative Breast NeoplasmsAnthracyclinesCyclophosphamideHumansRecombinational DNA RepairTaxoidsAnthracyclinesCyclophosphamideTaxoidsACT chemotherapyFailure-free intervalHomologous recombination repair deficiencyImmune checkpointTriple-negative breast cancer

Identifiers

PMID34465315
PMCPMC8408988
OpenAlexW3197098221

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.