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基于 DNA 损伤免疫反应和同源重组缺陷的三阴性乳腺癌双重预后分类。

Dual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency.

机构信息

University of Kansas Medical Center, Kansas City, KS.

SWOG Statistical Center, Seattle, WA.

出版信息

JCO Precis Oncol. 2023 Sep;7:e2300197. doi: 10.1200/PO.23.00197.

DOI:10.1200/PO.23.00197
PMID:37972336
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10681491/
Abstract

PURPOSE

Triple-negative breast cancer (TNBC) is a heterogeneous disease. We previously showed that homologous recombination deficiency (HRD) and the DNA damage immune response (DDIR) signature are prognostic in TNBC. We hypothesized that these biomarkers reflect related but not completely interdependent biological processes, that their combined use would be prognostic, and that simultaneous assessment of the immunologic microenvironment and susceptibility to DNA damaging therapies might be able to identify subgroups with distinct therapeutic vulnerabilities.

METHODS

We analyzed the dual DDIR/HRD classification in 341 patients with TNBC treated with adjuvant anthracycline-based chemotherapy on the SWOG S9313 trial and corroborated our findings in The Cancer Genome Atlas breast cancer data set.

RESULTS

DDIR/HRD classification is highly prognostic in TNBC and identifies biologically and immunologically distinct subgroups. Immune-enriched DDIR+/HRD+ TNBCs have the most favorable prognosis, and DDIR+/HRD- and DDIR-/HRD+ TNBCs have favorable intermediate prognosis, despite the latter being immune-depleted. DDIR-/HRD- TNBCs have the worst prognosis and represent an internally heterogeneous group of immune-depleted chemoresistant tumors.

CONCLUSION

Our findings propose DDIR/HRD classification as a potentially clinically relevant approach to categorize tumors on the basis of therapeutic vulnerabilities.

摘要

目的

三阴性乳腺癌（TNBC）是一种异质性疾病。我们之前表明，同源重组缺陷（HRD）和 DNA 损伤免疫反应（DDIR）特征与 TNBC 的预后相关。我们假设这些生物标志物反映了相关但并非完全相互依存的生物学过程，它们的联合使用具有预后价值，并且同时评估免疫微环境和对 DNA 损伤治疗的敏感性，可能能够识别具有不同治疗弱点的亚组。

方法

我们分析了在 SWOG S9313 试验中接受辅助蒽环类化疗治疗的 341 例 TNBC 患者的双重 DDIR/HRD 分类，并在癌症基因组图谱乳腺癌数据集进行了验证。

结果

DDIR/HRD 分类在 TNBC 中具有高度的预后价值，并确定了生物学和免疫学上不同的亚组。免疫富集的 DDIR+/HRD+ TNBC 具有最有利的预后，而 DDIR+/HRD-和 DDIR-/HRD+ TNBC 具有有利的中间预后，尽管后者免疫耗竭。DDIR-/HRD- TNBC 具有最差的预后，代表了一组具有内在异质性的免疫耗竭化疗耐药肿瘤。

结论

我们的研究结果表明，DDIR/HRD 分类可能是一种潜在的临床相关方法，可以根据治疗弱点对肿瘤进行分类。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4594/10681491/ef23ec1510ae/po-7-e2300197-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4594/10681491/ef23ec1510ae/po-7-e2300197-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4594/10681491/ef23ec1510ae/po-7-e2300197-g001.jpg

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