2024-10-22 アリゾナ大学
A new study has determined that a diagnostic test invented at the University of Arizona can potentially predict the likelihood of relapse or recurrence among patients with early-stage breast cancer.
Joshua Elz/University of Arizona Cancer Center
<関連情報>
- https://news.arizona.edu/news/clinical-study-confirms-tissue-stiffening-breast-cancer-can-drive-metastasis
- https://aacrjournals.org/clincancerres/article-abstract/doi/10.1158/1078-0432.CCR-24-1518/749050/High-Mechanical-Conditioning-by-Tumor
腫瘍細胞外マトリックスの硬さによる高い機械的コンディショニングは、HER2陰性乳癌における抗線維化療法の予測バイオマーカーである High Mechanical Conditioning by Tumor Extracellular Matrix Stiffness Is a Predictive Biomarker for Antifibrotic Therapy in HER2-Negative Breast Cancer
Miguel Quintela-Fandino;Begoña Bermejo;Esther Zamora;Fernando Moreno;José Ángel García-Saenz;Sonia Pernas;Noelia Martínez-Jañez;Desirée Jiménez;Encarna Adrover;Raquel de Andrés;Silvana Mourón;Maria J. Bueno;Luis Manso;Gemma Viñas;Emilio Alba;Antonio Llombart-Cussac;Javier Cortés;Cristina Tebar;Denise J. Roe;Adam Grant;Adam Watson;Ramon Colomer;Ghassan Mouneimne
Clinical Cancer Research Published:October 11 2024
DOI:https://doi.org/10.1158/1078-0432.CCR-24-1518
Abstract
Purpose:
Tumor progression has been linked to stiffening of the extracellular matrix caused by fibrosis. Cancer cells can be mechanically conditioned by stiff extracellular matrix, exhibiting a 1,004-gene signature [mechanical conditioning (MeCo) score]. Nintedanib has demonstrated antifibrotic activity in idiopathic pulmonary fibrosis. This study explores nintedanib’s antifibrotic effect on breast cancer outcomes.
Experimental Design:
We present long-term follow-up and analysis of a neoadjuvant randomized phase II trial in early HER2-negative breast cancer. Patients (N = 130) underwent a baseline biopsy and received 12 paclitaxel courses alone (control arm) or in combination with nintedanib (experimental arm). The tumor MeCo score was determined by RNA sequencing. The primary aim was to assess nintedanib’s impact on event-free survival based on MeCo scores.
Results:
Follow-up data were retrieved from 111 patients; 75 baseline and 24 post-run-in phase samples were sequenced. After median follow-up of 9.67 years, median event-free survival was not statistically different between arms (P = 0.37). However, in the control arm, high- versus low-MeCo patients had a statistically higher relapse risk: HR = 0.21; P = 0.0075. This risk was corrected by nintedanib in the experimental arm: HR = 0.37; P = 0.16. Nintedanib demonstrated pharmacodynamic engagement, reducing the MeCo score by 25% during the run-in phase (P < 0.01). Patients with low MeCo after run-in had the best long-term prognosis (HR = 0.087; P = 0.03).
Conclusions:
High MeCo is predictive of poor outcomes in HER2-negative early breast cancer, although this risk can be mitigated by nintedanib, which is able to specifically reduce MeCo.
