Chi-Cheng Huang1,2,3, Yi-Fang Tsai1,2,4, Chun-Yu Liu1,4,5, Ta-Chung Chao1,4,6, Pei-Ju Lien1,2, Yen-Shu Lin1,2, Chin-Jung Feng1, Jen-Hwey Chiu1,2,7, Chih-Yi Hsu8,9, Ling-Ming Tseng10,11,12. 1. Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan. 2. Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan. 3. Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan. 4. Faculty of Medicine, College of Medicine, National Yang-Ming University, Taipei, Taiwan. 5. Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 6. Division of Chemotherapy, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan. 7. Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. 8. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 9. School of Medicine, National Yang-Ming University, Taipei, Taiwan. 10. Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan. Lmtseng87@gmail.com. 11. Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan. Lmtseng87@gmail.com. 12. Faculty of Medicine, College of Medicine, National Yang-Ming University, Taipei, Taiwan. Lmtseng87@gmail.com.
Abstract
BACKGROUND: Breast cancer is one of the leading causes of cancer-related deaths in women, and there is a demand in developing an Asian-based genetic profiling database for breast cancer in improving the treatment response. This study aimed to determine molecular alternations and identify potential therapeutic targets by analyzing the genetic profiling from a cohort of Taiwanese breast cancers using a commercialized next-generation sequencing (NGS) targeted panel. METHODS: The study population comprised a broad spectrum of breast cancer patients in Taiwan, including Group 1: planned to receive first-line surgery and followed by adjuvant therapy, or early relapse within three years, Group 2: planned to receive first-line neoadjuvant therapy and followed by surgery, and Group 3: de novo stage IV, or stage IV with recurrence beyond three years. Molecular profiles were determined using Thermo Fisher™ Oncomine™ Comprehensive Assay version 3 (TMO comprehensive assay) from Formalin-Fixed Paraffin-Embedded (FFPE) tissues. Level of actionability was evaluated with the ESMO Scale of clinical actionability of molecular targets (ESCAT). RESULTS: A total of 380 TMO comprehensive assays were conducted on 372 patients, and we presented targeted sequencing analyses of Tier I: alteration-drug match associated with improved outcome in clinical trials including ERBB2 amplification, BRCA1/2 germline mutation, PIK3CA mutation, and NTRK translocation, and Tier II: antitumor activity associated with the matched alteration-drug but lack of prospective outcome data including PTEN loss, ESR1 mutation, AKT1 mutation, and ERBB2 mutation, and Tier III: matched drug-alteration that led to clinical benefit in another tumor type including MDM2 amplification, and ERBB3 mutation. Among them, 249 (66%) showed at least one actionable alternation based on the ESCAT criteria. The most frequent impacted genes (all variants combined within each sample) were PIK3CA (38%), followed by ERBB2 (23%), ESR1 (10%), AKT1 (6%), and BRCA2 (5%), and the remaining rare variants (less than 5% of assayed cohort) were BRCA1 (3%), MDM2 (2.2%), and ERBB3 (1.1%). 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.
BACKGROUND:Breast cancer is one of the leading causes of cancer-related deaths in women, and there is a demand in developing an Asian-based genetic profiling database for breast cancer in improving the treatment response. This study aimed to determine molecular alternations and identify potential therapeutic targets by analyzing the genetic profiling from a cohort of Taiwanese breast cancers using a commercialized next-generation sequencing (NGS) targeted panel. METHODS: The study population comprised a broad spectrum of breast cancerpatients in Taiwan, including Group 1: planned to receive first-line surgery and followed by adjuvant therapy, or early relapse within three years, Group 2: planned to receive first-line neoadjuvant therapy and followed by surgery, and Group 3: de novo stage IV, or stage IV with recurrence beyond three years. Molecular profiles were determined using Thermo Fisher™ Oncomine™ Comprehensive Assay version 3 (TMO comprehensive assay) from Formalin-Fixed Paraffin-Embedded (FFPE) tissues. Level of actionability was evaluated with the ESMO Scale of clinical actionability of molecular targets (ESCAT). RESULTS: A total of 380 TMO comprehensive assays were conducted on 372 patients, and we presented targeted sequencing analyses of Tier I: alteration-drug match associated with improved outcome in clinical trials including ERBB2 amplification, BRCA1/2 germline mutation, PIK3CA mutation, and NTRK translocation, and Tier II: antitumor activity associated with the matched alteration-drug but lack of prospective outcome data including PTEN loss, ESR1 mutation, AKT1 mutation, and ERBB2 mutation, and Tier III: matched drug-alteration that led to clinical benefit in another tumor type including MDM2 amplification, and ERBB3 mutation. Among them, 249 (66%) showed at least one actionable alternation based on the ESCAT criteria. The most frequent impacted genes (all variants combined within each sample) were PIK3CA (38%), followed by ERBB2 (23%), ESR1 (10%), AKT1 (6%), and BRCA2 (5%), and the remaining rare variants (less than 5% of assayed cohort) were BRCA1 (3%), MDM2 (2.2%), and ERBB3 (1.1%). CONCLUSION: Targeted sequencing of actionable genes is believed to provide clinical applicability and substantial benefits for Taiwanese breast cancerpatients. A valid scale of clinical actionability should be adopted for precision medicine practice under multidisciplinary molecular tumor board.
Entities:
Keywords:
Breast cancer; Next-generation sequencing; Precision medicine; Taiwan; Targeted panel
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