Abstract | PURPOSE: 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.
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Authors | 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 |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 29
Issue 23
Pg. 4908-4919
(12 01 2023)
ISSN: 1557-3265 [Electronic] United States |
PMID | 37733800
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | ©2023 American Association for Cancer Research. |
Chemical References |
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Topics |
- Humans
- Triple Negative Breast Neoplasms
(drug therapy, genetics, pathology)
- Treatment Outcome
- Disease-Free Survival
- Prognosis
- Chemotherapy, Adjuvant
(methods)
- Cyclophosphamide
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