Abstract 8P
Background
When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post NACT samples to predict relapse more accurately.
Methods
We identified 115 samples of residual tumors from post-NACT TNBC patients. We profiled the expression of 770 genes related to cancer microenvironment using the NanoString PanCancer IO360 panel to develop a prognostic transcriptomic signature, and to describe the immune microenvironments of the residual tumors.
Results
Thirty-eight (33%) patients experienced metastatic relapse. Hierarchical clustering separated patients into 5 clusters with distinct prognosis based on pathways linked to immune activation, epithelial to mesenchymal transition and cell cycle. Clusters enriched in immune activation had a significantly better prognosis. We selected eight immune-related genes (BLK, GZMM, CXCR6, LILRA1, SPIB, CCL4, CXCR4, SLAMF7) to develop a prognostic transcriptomic signature. We also developed an extended signature comprising 55 genes with a high correlation score (≥ 0.8) with at least one gene from the 8-gene signature. A high 8-gene signature score or extended signature score was associated with a significantly better distant-relapse free interval in our cohort (HR 0.18 [95%CI 0.09-0.35], P < 0.001 and HR 0.27 [95%CI 0.14-0.51], P < 0.001, respectively). Both signatures were tested on TNBC patients from METABRIC cohort (n = 251) and were associated with a better disease-specific survival (8-gene signature: HR 0.53 [95%CI 0.35-0.8], P < 0.01 and extended signature: HR 0.43 [95%CI 0.2- 0.64], P < 0.001). In our cohort, the 8-gene signature as well as the RCB score were validated as independent prognostic factors in multivariate analysis.
Conclusions
Lack of immune activation after NACT is associated with a high risk of distant relapse. We propose a prognostic signature based on immune infiltrate that could help select patients in need of adjuvant therapies.
Legal entity responsible for the study
Gaëtan MacGrogan.
Funding
Comité Prévention Dépistage des Cancers.
Disclosure
M. Arnedos: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Puma, AstraZeneca, AbbVie; Financial Interests, Institutional, Other, Masterclass: Roche, Genomic Health; Financial Interests, Institutional, Other, Preceptorship: Novartis; Financial Interests, Institutional, Invited Speaker: Novartis, Puma. H. Bonnefoi: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Bayer. All other authors have declared no conflicts of interest.