Abstract 196P
Background
The change in mutational landscape of TNBC patients with residual disease after neoadjuvant chemotherapy(NAC) might provide valuable insights into its biology and provide targets for therapy.
Methods
TNBC patients with residual disease after anthracycline taxane NAC +/- platinum were included. Archival paired (pre and post NAC) samples were processed for NGS with a custom-designed 72-gene panel. The sequences were aligned to human reference genome (GRCh37/hg19) using BWA program. Somatic mutations identified using UMI corrected .clc pipeline and LoFreq (v2) variant caller. Mutations annotated using in-house annotation pipeline (VariMAT). Gene annotation of the variants was performed using VeP program against the Ensembl release 90 human gene Model.
Results
25 patients treated from 2018-2019 were included. 72% patients had stage III disease. Among all 50 tumour samples (pre and post NAC), a median of 12 mutations per sample was observed. 73.5% were missense mutations. Post Platinum NAC an average of 12.8±7 gene mutations were seen and 11.3±5 gene mutations without platinum(p 0.94). Following platinum-NAC, the common genes mutated were TP53(81%), AR(62%), PTEN(62%), PMS2(43%) and ERBB2(33%). In post-NAC samples, private mutations were present only in the platinum group. The major differences between no platinum vs. platinum group was seen with AKT1 (50 vs. 14.3%; p 0.17), MSH6(50 vs. 14.3%; p 0.17), ERBB2(75 vs. 33.3%; p 0.16), HRAS(25 vs. 4.8%; p 0.3) and STK11 (0 vs. 33.3%; p 0.24). Five patients had recurrence of breast cancer. Post-NAC they had on average 14±7 mutated genes vs. 12.2±6 in those recurrence-free (p 0.49). Table: 196P
Proportion of patients with mutations
| Pre-NAC | Post-NAC |
| TP53(80%) | TP53(84%) |
| PMS2(64%) | AR(60%) |
| PTEN(64%) | PTEN(60%) |
| ERBB2(48%) | PMS2(44%) |
| NOTCH1(44%) | ERBB2(40%) |
| Recurrence-free | Recurrent disease |
| TP53(85%) | TP53(80%) |
| PTEN(65%) | AR(60%) |
| AR(60%) | ERBB2(60%) |
| PMS2(45%) | PMS2(45%) |
| SMARCA4(40%) | AKT1(40%) |
Conclusions
The somatic mutational profile was distinct comparing pre vs. post-NAC tumour samples, platinum vs. non-platinum NAC and recurrence vs. no recurrence. AR mutations were present in a higher proportion post-NAC. These findings need further elucidation in larger prospective studies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Institutional Review Board of the Christian Medical College, Vellore.
Funding
Christian Medical College Vellore Research Grant.
Disclosure
All authors have declared no conflicts of interest.