Differential Benefit of Metronomic Chemotherapy Among Triple-Negative Breast Cancer Subtypes Treated in the IBCSG Trial 22–00
Gespeichert in:
| Titel: | Differential Benefit of Metronomic Chemotherapy Among Triple-Negative Breast Cancer Subtypes Treated in the IBCSG Trial 22–00 |
|---|---|
| Autoren: | Andrea Joaquin Garcia, Mattia Rediti, David Venet, Samira Majjaj, Roswitha Kammler, Elisabetta Munzone, Lorenzo Gianni, Beat Thürlimann, István Laáng, Marco Colleoni, Sherene Loi, Giuseppe Viale, Meredith M. Regan, Laurence Buisseret, Françoise Rothé, Christos Sotiriou |
| Quelle: | Clinical Cancer Research. 29:4908-4919 |
| Verlagsinformationen: | American Association for Cancer Research (AACR), 2023. |
| Publikationsjahr: | 2023 |
| Schlagwörter: | Triple Negative Breast Neoplasms, Sciences bio-médicales et agricoles, Prognosis, Triple Negative Breast Neoplasms -- drug therapy -- genetics -- pathology, Disease-Free Survival, 3. Good health, Adjuvant -- methods, Treatment Outcome, Chemotherapy, Adjuvant, Chemotherapy, Humans, Cyclophosphamide |
| Beschreibung: | 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. |
| Publikationsart: | Article |
| Dateibeschreibung: | 1 full-text file(s): application/pdf |
| Sprache: | English |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-23-1267 |
| Zugangs-URL: | https://pubmed.ncbi.nlm.nih.gov/37733800 |
| Dokumentencode: | edsair.doi.dedup.....72ee70a9e39bf3eaf4d980986f584e0e |
| Datenbank: | OpenAIRE |
Nájsť tento článok vo Web of Science | 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. |
|---|---|
| ISSN: | 15573265 10780432 |
| DOI: | 10.1158/1078-0432.ccr-23-1267 |