Mesenchymal-like immune-altered is the fourth robust triple-negative breast cancer molecular subtype.

Autor: Jézéquel P; Institut de Cancérologie de l'Ouest, 44805, Saint Herblain, France. pascal.jezequel@ico.unicancer.fr.; Nantes Université, Univ Angers, INSERM, CNRS, CRCI2NA, 44000, Nantes, France. pascal.jezequel@ico.unicancer.fr.; Équipe Labellisée LIGUE Contre Le Cancer CRCI2NA, 44000, Nantes, France. pascal.jezequel@ico.unicancer.fr., Lasla H; Institut de Cancérologie de l'Ouest, 44805, Saint Herblain, France., Gouraud W; Institut de Cancérologie de l'Ouest, 44805, Saint Herblain, France., Basseville A; Institut de Cancérologie de l'Ouest, 44805, Saint Herblain, France., Michel B; Nantes Université, École Centrale Nantes, CNRS, Laboratoire de Mathématiques Jean Leray, LMJL, UMR 6629, 44000, Nantes, France., Frenel JS; Institut de Cancérologie de l'Ouest, 44805, Saint Herblain, France.; Nantes Université, Univ Angers, INSERM, CNRS, CRCI2NA, 44000, Nantes, France.; Équipe Labellisée LIGUE Contre Le Cancer CRCI2NA, 44000, Nantes, France., Juin PP; Nantes Université, Univ Angers, INSERM, CNRS, CRCI2NA, 44000, Nantes, France.; Équipe Labellisée LIGUE Contre Le Cancer CRCI2NA, 44000, Nantes, France., Ben Azzouz F; Institut de Cancérologie de l'Ouest, 44805, Saint Herblain, France., Campone M; Institut de Cancérologie de l'Ouest, 44805, Saint Herblain, France.; Nantes Université, Univ Angers, INSERM, CNRS, CRCI2NA, 44000, Nantes, France.; Équipe Labellisée LIGUE Contre Le Cancer CRCI2NA, 44000, Nantes, France.; Université d'Angers, 49000, Angers, France.
Jazyk: angličtina
Zdroj: Breast cancer (Tokyo, Japan) [Breast Cancer] 2024 Sep; Vol. 31 (5), pp. 825-840. Date of Electronic Publication: 2024 May 22.
DOI: 10.1007/s12282-024-01597-z
Abstrakt: Background: Robust molecular subtyping of triple-negative breast cancer (TNBC) is a prerequisite for the success of precision medicine. Today, there is a clear consensus on three TNBC molecular subtypes: luminal androgen receptor (LAR), basal-like immune-activated (BLIA), and basal-like immune-suppressed (BLIS). However, the debate about the robustness of other subtypes is still open.
Methods: An unprecedented number (n = 1942) of TNBC patient data was collected. Microarray- and RNAseq-based cohorts were independently investigated. Unsupervised analyses were conducted using k-means consensus clustering. Clusters of patients were then functionally annotated using different approaches. Prediction of response to chemotherapy and targeted therapies, immune checkpoint blockade, and radiotherapy were also screened for each TNBC subtype.
Results: Four TNBC subtypes were identified in the cohort: LAR (19.36%); mesenchymal stem-like (MSL/MES) (17.35%); BLIA (31.06%); and BLIS (32.23%). Regarding the MSL/MES subtype, we suggest renaming it to mesenchymal-like immune-altered (MLIA) to emphasize its specific histological background and nature of immune response. Treatment response prediction results show, among other things, that despite immune activation, immune checkpoint blockade is probably less or completely ineffective in MLIA, possibly caused by mesenchymal background and/or an enrichment in dysfunctional cytotoxic T lymphocytes. TNBC subtyping results were included in the bc-GenExMiner v5.0 webtool ( http://bcgenex.ico.unicancer.fr ).
Conclusion: The mesenchymal TNBC subtype is characterized by an exhausted and altered immune response, and resistance to immune checkpoint inhibitors. Consensus for molecular classification of TNBC subtyping and prediction of cancer treatment responses helps usher in the era of precision medicine for TNBC patients.
(© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)
Databáze: MEDLINE
Externí odkaz: