Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy combined with anti-EGFR antibodies [Nanostring]

To find metastatic recurrence biomarkers of triple negative breast cancer (TNBC) treated by neoadjuvant chemotherapy and anti-EGFR antibodies (NAT), we evaluated tumor genomic, transcriptomic and immune features, using MSK-IMPACT assay, gene arrays, Nanostring technology and TIL assessment on H&E. Six patients experienced a rapid fatal recurrence (RR) and other 6 had later non-fatal recurrences (LR). Before NAT, RR had low expression of 6 MHC class I and 13 MHC class II genes but were enriched in upregulated genes involved in the cell cycle-related pathways. Their TIL number before NAT in RR was very low (<5%) and did not increase after treatment. In post-NAT residual tumors, RR cases showed high expression of SOX2 and CXCR4. Our results indicate that high expression of cell cycle genes, combined with cold immunological phenotype, may predict strong TNBC resistance to NAT and rapid progression after it. This biomarker combination is worth validation in larger studies. Nucleic acids were extracted from frozen tumor tissue (pre-NAT samples) using AllPrep DNA/RNA mini kit (Qiagen France SAS, Courtaboeuf, France) according to the manufacturer’s protocol. RNA quality was verified using the 2100 BioAnalyzer (Agilent Technologies). The extracted material was sent to Helixio (Saint-Beauzire, France), where it was hybridized with gene arrays (Human SurePrint, Agilent Technologies France, Les Ullis, France).