American Association for Cancer Research
ccr-23-1267_supplementary_figure_s3_suppfs3.pdf (77.66 kB)

Supplementary Figure S3 from Differential Benefit of Metronomic Chemotherapy Among Triple-Negative Breast Cancer Subtypes Treated in the IBCSG Trial 22–00

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posted on 2023-12-01, 08:43 authored by 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

Kaplan-Meier estimates for OS, DRFI and BCFI measures between CM and no-CM cohorts across the Bareche TNBC molecular subtypes.


Fonds De La Recherche Scientifique - FNRS (FNRS)

Stichting Tegen Kanker (Fondation Contre le Cancer)


Fondation Rose et Jean Hoguet (Rose and Jean Hoguet Foundation)



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. 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. 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). 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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