Abstract PO3-08-10: Somatic mutations of a multigene panel in Chinese HER2-positive patients undergoing neoadjuvant therapy and impact on prognosis based on TP53 status:a single-institution retrospective cohort
Authors: Xiong Min , Wangxu Liren , Xue Jingyan , Yang Benlong , Wu Jiong 
Published: May 2024

Abstract
Background: Gene mutations and copy number variations (CNVs) are associated with the occurrence and development of tumors. Neoadjuvant therapy (NAT) has shown greater clinical benefit in the treatment of HER2-positive breast cancer (BC). The impact of genetic mutations on NAT efficacy in BC has been frequently reported, but the relationship between genetic mutations and NAT efficacy and the long-term prognosis in HER2-positive BC patients still requires more high-quality studies. Methods: This retrospective cohort study was conducted patients receiving NAT between September 2017 and March 2021 in the Department of Breast Surgery of Fudan University Shanghai Cancer Center (FUSCC). The genomic characteristics of 513 cancer-related genes from the archived tumour blocks were assessed by next-generation sequencing (NGS). The relationship between tumour mutated gene and the postoperative pathological complete response (pCR) as well as prognosis of the disease-free survival (DFS) were further explored.Statistical methods included Chi-square test, fisher's exact test, Kaplan-Meier survival analysis, all of which were completed by SPSS 20.0. Results: 208(47.8%) patients achieved pCR after HER2-targeted NAT and 40(9.2%) patients encountered DFS events. The frequency of somatic alterations in TP53(60%), PIK3CA (15%) and ERBB2(11%) was highest in women with HER2-positive breast cancer. KMT2C (P= 0.036) and TP53(P=0.037) mutations were significantly increased in patients with DFS events. In the HER2+/HR- cohort, patients who achieved pCR had significantly benefit in prognosis (HR=3.605, P=0.002), and CCND1 amplifications(p=0.014), ATM(p=0.016) and GATA3(p=0.016) mutations were more frequent. ERBB2 mutations were significantly associated with younger ages of diagnosis(p=0.018). TP53 mutations were associated with worse DFS (HR=3.242, P=0.0110) as well as more DFS events(p=0.048). Furthermore, TP53 mutations had significant prognostic importance in HER2-positive BC patients with HR-negative (HR=3.712, P=0.0266), pCR (HR=6.253, P=0.0268) and who received trastuzumab-only targeted therapy (HR=4.145, P=0.0105). Conclusions: Regard to diverse hormone receptor status or neoadjuvant efficacy, the genetic mutation maps of Chinese HER2+ patients receiving NAT are disparate. Our study found that TP53 mutations have significant prognostic value in patients with NAT for HER2-positive BC and patients benefit differently depending on HR status, neoadjuvant regimens and response.
Citation Format: Min Xiong, Liren Wangxu, Jingyan Xue, Benlong Yang, Jiong Wu. Somatic mutations of a multigene panel in Chinese HER2-positive patients undergoing neoadjuvant therapy and impact on prognosis based on TP53 status:a single-institution retrospective cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-10.