Differential Benefit of Metronomic Chemotherapy Among Triple-Negative Breast Cancer Subtypes Treated in the IBCSG Trial 22-00
- Author(s)
- Joaquin Garcia, A; Rediti, M; Venet, D; Majjaj, S; Kammler, R; Munzone, E; Gianni, L; Thürlimann, B; Laáng, I; Colleoni, M; Loi, S; Viale, G; Regan, MM; Buisseret, L; Rothé, F; Sotiriou, C;
- Details
- Publication Year 2023-12-01,Volume 29,Issue #23,Page 4908-4919
- Journal Title
- Clinical Cancer Research
- Publication Type
- Research article
- Abstract
- PURPOSE: To explore whether specific triple-negative breast cancer (TNBC) molecular subtypes are predictive for a benefit from maintenance low-dose cyclophosphamide and methotrexate (CM) in the adjuvant IBCSG 22-00 phase III clinical trial. EXPERIMENTAL DESIGN: RNA sequencing was performed on a selection of 347 TNBC formalin-fixed paraffin-embedded (FFPE) tumor samples following a case-cohort-like sampling. TNBC subtypes were computed on gene expression data. The association between TNBC subtypes and treatment outcome was assessed using a Cox proportional-hazards interaction test. RESULTS: Immunomodulatory (IM) and basal-like/immune activated (BLIA) molecular subtypes showed a significant survival benefit when treated with low-dose CM [disease-free survival (DFS): HR, 0.5; 95% confidence interval (CI), 0.28-0.89; Pinteraction = 0.018 and HR, 0.49; 95% CI, 0.27-0.9; Pinteraction = 0.021]. Moreover, a high expression of regulatory T-cell immune signature was associated with a better prognosis in the CM arm, in line with a potential immunomodulating role of cyclophosphamide. In contrast, a worse outcome was observed in tumors with a mesenchymal (M) subtype treated with low-dose CM (DFS: HR, 1.9; 95% CI, 1.2-3; Pinteraction = 0.0044). CONCLUSIONS: Our results show a differential benefit of low-dose CM therapy across different TNBC subtypes. Low-dose CM therapy could be considered as a potential strategy for TNBC tumors with IM subtype in the early-disease setting.
- Keywords
- Humans; *Triple Negative Breast Neoplasms/drug therapy/genetics/pathology; Treatment Outcome; Disease-Free Survival; Prognosis; Chemotherapy, Adjuvant/methods; Cyclophosphamide
- Department(s)
- Medical Oncology; Laboratory Research
- Publisher's Version
- https://doi.org/10.1158/1078-0432.Ccr-23-1267
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-01-19 03:10:18
Last Modified: 2024-07-09 06:23:18