Abstract 257: Tumor mutation burden of Egyptian breast cancer patients based on next generation sequencing
Authors: Nassar Auhood , Lymona Ahmed M. , Lotfy Mai M. , El-Din Youssef Amira Salah , Zekri Abdel-Rahman N. 
Published: July 2021

Abstract
Tumor mutation burden of Egyptian breast cancer patients based on next generation sequencing Aim: This study aimed to identify the tumor mutation burden (TMB) value in Egyptian Breast cancer (BC) patients. Additionally, we aimed to find the best model to predict TMB value by the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and proliferative index Ki-67, to help expecting the prognosis of patients and predicting the possible response to immunotherapy. Patients and methods: In 58 Egyptian patients with BC, the Ion AmpliSeq Comprehensive Cancer Panel based on NGS was used to determine the TMB value of primary tumor tissues of Egyptian BC patients. The predicted TMB value was divided into 4 groups: A (0.00-0.625), B (0.626-1.25), C (1.251-2.50), and D (&gt;2.50), according to the quartile method, with group A as reference level. Different machine learning models were used to select the optimal classification model. Results: The measured TMB value was between 0 and 8.12/Mb. The TMB distribution among the studied 58 cases was: 19 cases in group A, 12 cases in group B, 14 cases in group C, and 13 cases in group D. ER positive expression was significantly associated with TMB ≤ 1.25 (ER positive vs ER-negative, OR =0.35, 95% CI: 0.04-2.98, p= 0.001). TMB ≤1.25 was significantly distributed in patients with PR positive expression (PR positive versus PR negative, OR = 0.17, 95% CI= 0.02-0.44, p= 0.002). Ki67 expression positive was significantly associated with TMB &gt;1.25 than those who were Ki-67 expression negative (Ki67 positive versus Ki67 negative, OR = 9.33, 95% CI= 2.07-42.18, p= 0.004). Also, TMB &gt;1.25 was significantly distributed in triple negative (TN) patients than non-TN patients (OR=9.69, 95% CI: 1.05-89.9, p=0.045). However, no significant differences were observed between HER2 positive and HER2 negative group (OR = 2.47, 95% CI: 0.64-9.54, p =0.19). The adjusted Pseudo-R2 was 0.329 (P&lt;0.001). The optimized logistic regression model was TMB = -27.5 -1.82 ER - 0.73 PR + 0.826 HER2 + 2.08 Ki67. Conclusion: the preliminary findings of our studied sample set revealed that level of TMB in Egyptian BC patients is relatively low. Also, TMB value in hormone receptor positive and Ki-67 expression positive Egyptian BC patients is higher than hormone receptor negative and Ki-67 expression negative patients. Moreover, TMB value can be predicted based on the expression level of ER, PR, HER-2, and Ki-67. The optimized logistic regression model was TMB = -27.5 -1.82 ER - 0.73 PR + 0.826 HER2 + 2.08 Ki67.
Citation Format: Auhood Nassar, Ahmed M. Lymona, Mai M. Lotfy, Amira Salah El-Din Youssef, Abdel-Rahman N. Zekri. Tumor mutation burden of Egyptian breast cancer patients based on next generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 257.