Abstract P5-13-31: Pik3ca mutations and myc amplification are associated with pathological complete response in human epidermal growth factor receptor 2-positive breast cancer patients receiving pyrotinib combined with trastuzumab neoadjuvant treatment

Abstract

Abstract Background: Our previous study reported a good efficacy and safety of pyrotinib combined with trastuzumab neoadjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. We further explored the potential biomarkers for the efficacy of pyrotinib combined with trastuzumab neoadjuvant treatment in HER2-positive breast cancer patients. Methods:To date, a total of 162 patients with early-stage breast cancer were enrolled for the neoadjuvant pyrotinib combined with trastuzumab treatment clinical trial (ChiCTR1900022293). By the method of 425 genes next-generation sequencing (NGS), the genomic characteristics of them were evaluated for the potential correlation with postoperative pathological complete response (pCR). Results:. Among the cohort of 162 cases, a total of 43 patients have completed the whole therapy as well as final surgery and acquired qualified sequencing analysis report, and 25 of them achieved total pCR. The most frequently mutated driver genes were TP53 (80%), PIK3CA (46%), ERBB2 (10%), NF1 (8%), NBN (8%), ATRX (8%), respectively. In terms of somatic copy number alterations, the most frequent alterations are gain or amplification of ERBB2 (66%), MYC (24%), CKD12 (14%), CCND1 (12%) and ZNF217 (12%), respectively. The median tumor mutation burden (TMB) was 4.76 mut/Mb (0.00-29.61). Compared with pCR populations, non-pCR populations had higher median TMB but not statistically significant (5.29 vs 3.85 mut/Mb, P=0.141). In addition, the pCR rate of patients with wild-type PIK3CA is significantly higher than that of patients with mutated PIK3CA (80.0% vs 27.8%, P = 0.001), and those with amplified MYC are more likely to achieve pCR (22.2% vs 67.6%, P = 0.023). Conclusions:Preliminary results suggested that HER2-positive breast cancer patients with activating mutations in PIK3CA and amplified MYC are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy, which need larger sample size to validate. Citation Format: Qiyun Shi, Juncheng Xuhong, Jia Ge, Feng Liu, Yang Lan, Yi Zhang, Luo Tao, Xiuwu BIan, Xiaowei Qi, Jun Jiang. Pik3ca mutations and myc amplification are associated with pathological complete response in human epidermal growth factor receptor 2-positive breast cancer patients receiving pyrotinib combined with trastuzumab neoadjuvant treatment [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-31.