人表皮生长因子受体2阴性乳腺癌患者治疗中期肿瘤RNA高度破坏与新辅助化疗后无病生存期改善相关。

High mid-treatment tumour RNA disruption in patients with HER2-negative breast cancer is associated with improved disease-free survival after neoadjuvant chemotherapy.

作者信息

Parissenti Amadeo M, Pritzker Laura B, Dahle Maria Aanesland, Gythfeldt Hedda von der Lippe, Masilamani Twinkle, Theriault Gabriel, St-Onge Renée, D'costa Lavina, Lingjaerde Ole Christian, Haugen Mads Haugland, Engebraaten Olav

机构信息

School of Natural Sciences, Laurentian University, Sudbury, Canada.

Rna Diagnostics, Inc, Sudbury, Canada.

出版信息

Breast Cancer Res. 2025 Aug 11;27(1):143. doi: 10.1186/s13058-025-02092-9.

DOI:10.1186/s13058-025-02092-9

PMID:40790765

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12337404/

Abstract

BACKGROUND

High tumour ribosomal RNA degradation (RNA disruption) during neoadjuvant chemotherapy has been associated with a post-treatment pathologic complete response (pCR) and improved disease-free survival (DFS) in breast cancer patients. We further assessed the relationship between tumour RNA disruption or other metrics and neoadjuvant chemotherapy outcome using data from the NeoAva clinical trial (NCT00773695).

METHODS

Patients with early HER2-negative breast cancer received FEC-T chemotherapy ± bevacizumab in a randomized fashion. Biopsies were taken pre-treatment and after 12 and 25 weeks of chemotherapy. RNA and proteins extracted from the biopsies were used to compute the RNA disruption index (RDI) and to quantify levels of 210 proteins using protein array analysis at 12 weeks.

RESULTS

Tumour RDI values were higher mid- and post-treatment than pre-treatment ( < 0.0001). Patients with tumour RDI values > 1.1 exhibited higher disease-free and breast cancer-specific survival than patients with RDI values ≤ 1.1 ( = 0.049 and 0.031, respectively). While RDI values were higher for patients on the bevacizumab-containing regimen ( = 0.003), this was not associated with improved survival. Survival on either regimen was not significantly associated with a post-treatment pCR or an improved residual cancer burden (RCB) score. Significant differences in apoptotic, EMT, Notch, G1-S checkpoint, and DNA damage response pathways were seen between high- and low-RDI tumours.

CONCLUSIONS

High tumour RNA disruption during neoadjuvant chemotherapy was associated with improved DFS and may better predict outcome than the post-treatment pCR rate or RCB. If validated as an independent predictor of chemotherapy outcome, RNA disruption assessments during treatment may prove informative in making treatment escalation or de-escalation decisions.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s13058-025-02092-9.

摘要

背景

新辅助化疗期间肿瘤核糖体RNA降解（RNA破坏）与乳腺癌患者治疗后病理完全缓解（pCR）及无病生存期（DFS）改善相关。我们利用NeoAva临床试验（NCT00773695）的数据进一步评估肿瘤RNA破坏或其他指标与新辅助化疗结果之间的关系。

方法

早期HER2阴性乳腺癌患者以随机方式接受FEC-T化疗±贝伐单抗治疗。在化疗前、化疗12周和25周后进行活检。从活检组织中提取的RNA和蛋白质用于计算RNA破坏指数（RDI），并在12周时使用蛋白质阵列分析对210种蛋白质的水平进行定量。

结果

治疗中和治疗后的肿瘤RDI值高于治疗前（<0.0001）。肿瘤RDI值>1.1的患者比RDI值≤1.1的患者表现出更高的无病生存期和乳腺癌特异性生存期（分别为=0.049和0.031）。虽然接受含贝伐单抗方案治疗的患者RDI值更高（=0.003），但这与生存期改善无关。两种方案的生存期与治疗后pCR或残余癌负担（RCB）评分改善均无显著相关性。高RDI和低RDI肿瘤在凋亡、上皮-间质转化、Notch、G1-S检查点和DNA损伤反应途径方面存在显著差异。