Abstract 267P
Background
Shrinkage modes after neoadjuvant chemotherapy (NAC) related to the extent of the tumour is important to assess the odds of breast-conserving surgery. However, currently there is no adequate clinical biomarker that predicts the shrinkage modes after NAC.
Methods
We analysed pre- and post- treatment FFPE samples from 24 patients to measure the mutation profiles using the targeted next-generation sequencing approach with a 457 cancer-related gene panel. Pathological shrinkage mode was reconstructed in three dimensions after surgery and the genetic heterogeneity level was estimated by mutant-allele tumour heterogeneity (MATH). We measured the genetic intra-tumour heterogeneity (ITH) and explored its correlation with the shrinkage mode after NAC.
Results
The most common mutated genes were TP53 and PIK3CA, in both pre- and post- NAC samples. No recurrent mutations were significantly associated with the shrinkage mode. MATH value of FFPE samples before and after NAC treatment were analysed by area under the curve (AUC) of the receiver operating characteristic (ROC), and we found that 58 could be used as the MATH value threshold to distinguish the concentric shrinkage mode (CSM) and non-concentric shrinkage mode (NCSM) in NAC. We found that 3/4 patients in luminal A group, 5/7 in luminal B group, 7/8 in the HER2 positive group, 2/2 in the triple-negative group and 5/5 in the hybrid group had at least one MATH value under the threshold. Patients with a hybrid subtype had a higher proportion of CSM. 5/7 patients of luminal B patients, 5/8 of HER2 positive patients and 4/5 of hybrid patients had decreased MATH values after NAC treatment. Meanwhile, the MATH values of 3/4 luminal A patients and 1/2 triple-negative patients were raised after NAC treatment.
Conclusions
MATH value was associated with the shrinkage mode of breast cancer in a nonlinear model. Patients with the MATH value below the cut-off line (58) before and after NAC showed a concentric shrinkage mode. Our findings provide a promising application of the genome-based stratification to evaluate NAC effects in breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Yongsheng Wang.
Funding
Has not received any funding.
Disclosure
W. Wu: Full/Part-time employment: Berry Oncology Corporation. J. Wang: Full/Part-time employment: Berry Oncology Corporation. All other authors have declared no conflicts of interest.