Abstract 2503: Molecular profiling of Taiwanese breast cancers reveals potential therapeutic targets: Preliminary results of 160 subjects
Authors: Huang Chi-Cheng , Liu Chun-Yu , Tseng Ling-Ming 
Published: September 2020

Abstract
Introduction: Breast cancer is one of the leading causes of cancer-related death in women, and the annual incidence of breast cancer has continuously increased throughout the past two decades in Taiwan. There is a demand in developing an Asian-based genetic profiling database for breast cancer in improving the treatment response and recurrence rate. This study aimed to determine the difference of molecular alternations and identify the potential biomarkers regarding therapeutic target by analyzing the genetic profiling from a large cohort of breast cancer subjects using the method of next-generation sequencing (NGS).
Materials and methods: The protocol consisted of three years enrollment and approximately four years follow-up after enrollment. Individual subject was assigned into Group 1 [planned to received surgery as first-line treatment and followed by adjuvant therapy, Group 2 [planned to receive neoadjuvant therapy as the first-line treatment and followed by surgery], and Group 3 [diagnosed with de novo and treatment naïve stage IV breast cancer, or stage IV breast cancer with recurrence beyond three years after surgery]. Molecular profiling and potential biomarkers were determined using Thermo FisherTM OncomineTM Comprehensive Assay version 3 (TMO comprehensive assay) from Formalin-Fixed Paraffin-Embedded (FFPE) tissues.
Results: We presented the initial 160 subjects as preliminary results. The TMO comprehensive assay is a targeted, NGS assay that enables the detection of relevant SNVs, CNVs, gene fusions, and indels from 161 unique genes to help inform drug discovery research and clinical trial research programs such as the NCI-MATCH trial. Level of actionability of sequenced targets were evaluated with ESMO Scale of clinical actionability of molecular targets (ESCAT). Of note, Tier I [alteration-drug match associated with improved outcome in clinical trials], Tier II [antitumor activity associated with the matched alteration-drug but lack of prospective outcome data], and Tier III [matched drug-alteration that led to clinical benefit in another tumor type] matched targets including ERBB2 amplification, BRCA1/2 germline mutation, PIK3CA mutation, NTRK translocation (Tier I), PTEN loss, ESR1 mutation, AKT1 mutation, ERBB2 mutation (Tier II), and BRCA1/2 somatic mutation, MDM2 amplification, and ERBB3 mutation (Tier III) were retrieved and analyzed. 108 out of 160 sequenced subjects (67.5%) reported as least one variant (average 1.7 per case, ranged from 1 to 10). Two group 3 heavily pre-treated patients were identified to have all actionable genes varied. Ipatasertib, alpelisib, and talazoparib, for instance, had been advocated for the corresponding PTEN p.(Q219*), PIK3CA p.(G118S), and BRCA2 p.(Q1107*) mutations.
Conclusion: Targeted sequencing of actionable genes is believed to provide clinical applicability and substantial benefits for Taiwanese breast cancer patients. A valid scale of clinical actionability should be adopted for precision medicine practice under multidisciplinary molecular tumor board. Further details will be updated when more samples are ready for sequencing and actionability analyses in coming years.
Citation Format: Chi-Cheng Huang, Chun-Yu Liu, Ling-Ming Tseng. Molecular profiling of Taiwanese breast cancers reveals potential therapeutic targets: Preliminary results of 160 subjects [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2503.