FACO Poster Session
A small percentage of primary breast cancer shows high tumor mutation burden and may benefit from immune checkpoint inhibitor therapy
演題番号 : FP1-12
1:Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China、2:Department of Gastrointestinal Colorectal and Anal Surgery, China- Japan Union Hospital of Jilin University, China
Targeted therapy using immune checkpoint inhibitors (ICIs) like PD1 or PD-L1 antibodies is a breakthrough in cancer treatment in the last decade. However, in most tumor types including breast cancer, the response is not as optimistic. Tumor Mutation Burden (TMB) has been shown to be a sensitive marker for ICI treatment. This study is to investigate whether TMB could be used as a biomarker for breast cancer immunotherapy.
Two large cohorts of next generation sequencing studies of breast cancer were included in our analysis. One study entitled METABRIC performed targeted sequencing of 173 cancer-related genes in around 2500 primary breast cancer tissues. The other study was from TCGA breast cancer project, which performed Whole Exome Sequencing (WES) of around 1000 primary breast cancer samples. Mutation data was downloaded from public data deposit. The number of mutations per sample was calculated. TMB was calculated by dividing the coverage in million base pairs from that of the total mutation counts.
In METABRIC study, 17272 mutations were identified in 2369 samples, with a median of 7 mutations per sample (95% CI: 6 ~ 7). The median TMB of METABRIC dataset was 5.8 SNVs/Mb (95% CI: 5 ~ 5.8). Totally 30 out 2369 (1.3%) samples had a TMB equal or larger than 20 SNVs/Mb. In another cohort from TCGA breast cancer study using WES technology, 90172 mutations were identified in 977 samples, with a median of 44 mutations per sample (95% CI: 39 ~ 50). The median TMB was 1 SNVs/Mb (95% CI: 0.9 ~ 1.1). Totally 13 out 977 (1.3%) samples had a TMB equal or large than 20 SNVs/Mb.
Breast cancer shows middle to low mutation burden compared to other cancer types. Around 1.3% of breast cancer has quite high TMB of at least 20 SNVs/Mb, which may be qualified for immune checkpoint inhibitors therapy. Our study indicates that TMB may be incorporated as standard test for late stage breast cancer patients in the clinical practice.