Abstract 5084: KMT2D and PIK3CA mutation as potential factors to predict adjuvant chemotherapy efficacy in surgical triple negative breast cancer

Abstract

Abstract Background: Chemotherapy is the most common treatment strategy for triple negative breast cancer (TNBC) patients. Nevertheless, due to adverse drug reactionsthe molecular high heterogeneity of TNBC and no appropriate meaningful efficacy markers, it is still difficult to establish preferred therapeutic strategies and predict the outcomes for TNBC. This study was to investigate the potential predictors and therapeutic targets based on genetic features. Methods: A total of 386 TNBC patients were randomized 1:1 to receive either six cycles of paclitaxel + cisplatin (TP) or four cycles of epirubicin + cyclophosphamide followed by four cycles of docetaxel (EC-T) adjuvant chemotherapy after surgery (NCT01150513), which were described previously. Finally, 149 TNBC patients with clinical and tumor sequencing data availability were retrospectively analysed by NGS for 733 cancer-related genes. All tumor samples were collected during the surgical operation and subjected to NGS for evaluating genomic mutations and the potential predictors. Cox regression model and Kaplan-Meier method were applied to evaluate disease-free survival (DFS). Results: In the surgical cohort receiving adjuvant chemotherapy, 74 patients received platinum and 75 received platinum-free chemotherapy as adjuvant chemotherapy. The most frequently mutated genes in this surgical TNBC cohort were TP53 (84%), BRCA1 (18%), BRCA2 (15%), POL1 (13%), PTEN (12%), REV3L (11%), FANCC (10%), and PARP4 (10%). We analyzed the associations between 733 cancer-related gene mutations and DFS after adjuvant chemotherapy. For the TP group, PIK3CA mutation (19%, 14/74) was discovered to correlate with poor DFS for patients treated with platinum-containing adjuvant therapy (HR=3.2, P=0.037), and KMT2D mutation (15%, 11/75) display worse DFS for patients treated with EC-T platinum-free group (HR=3.0, p=0.039). However, BRCA1/2 mutation (24%, 35/149) was found to be associated with poor prognosis (HR=2.1 (95% CI: 1-4.6), p=0.047), irrespective of therapeutic regimen. Conclusions: In this population of surgical TNBC patients, NGS analysis identified potential predictive markers. PIK3CA mutation in TP platinum-containing group and KMT2D mutation in EC-T platinum-free group were significantly associated to poor prognosis for adjuvant chemotherapy in triple negative breast cancer. Citation Format: Xue Wang, Feng Du, Jian Yue, Yiran Si, Lina Cui, Bei Zhang, Xiaochen Zhao, Binghe Xu, Peng Yuan. KMT2D and PIK3CA mutation as potential factors to predict adjuvant chemotherapy efficacy in surgical triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5084.