Abstract 43P
Background
Neoadjuvant chemoimmunotherapy with immune checkpoint blockers (ICBs) is the standard approach to treat early triple-negative breast cancer (TNBC). However, the pathological complete response (pCR) rate is around 65% suggesting that immunosuppressive tumor microenvironment (TME) cannot be reverted with the use of anti PD1/PDL1 immunotherapy alone. To identify patients who benefit from immunotherapy compared to those who do not and whether chemotherapy (CT) was able to revert the immunosuppressive TME, we conducetd a comprehensive analysis on a retrospective case series of tumors pre and post neo adjuvant CT (naCT) using gene expression profiling.
Methods
RNA was extracted from biopsies collected before and after doxorubicin based naCT in 19 patients with grade 3 TNBC who did not achieve pCR. Gene expression analysis was conducted using the NanostringPanCancerImmune Panel on the nCounter platform. Data normalization was performed with nSolver 4.0.
Results
The Expanded Immune Gene Signature, described by Ayers (JCI 2017), was applied to our dataset. Patients were categorized into 4 groups based on signature level changes before and after naCT: high pre-treatment levels that decreased post-treatment (n=7), high pre-treatment levels that increased (n=2), low pre-treatment levels that increased (n=5) and low pre-treatment levels that decreased (n=5). By analyzing the relationship between pre-treatment expression levels of individual genes and post-treatment signature trends, IL17RB emerged as the most significant gene to distinguish patients with increasing signature trends from those with decreasing ones. Notably, among patients with low pre-treatment signature levels (n = 10), those with a decreasing trend had consistently higher pre-CT IL17RB expression levels (n = 5) compared to those with an increasing trend (n = 5).
Conclusions
Gene expression analysis conducted prior to naCT may help identify patients who are likely to benefit from ICBs versus those who require CT to overcome an immunosuppressive TME. Pre-naCT IL17RB expression levels may serve as a predictor for distinguishing patients in whom naCT can revert the immunosuppressive TME. Further analysis of larger datasets is ongoing to validate these preliminary findings.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
ERANET TRANSCAN JTC 2015.
Disclosure
All authors have declared no conflicts of interest.