Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world

Sep 21, 2026

Uploaded by Hazel

Retrospective review of 1154 cancer patients undergoing germline genetic testing at a Singapore centre from 2000–2022 assessed the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. Most testing used multi-gene panels. Four hundred and eleven patients (35.6%) carried a PGV, and 334 (81%) were clinically actionable. Among advanced cancer patients, 79 received germline-directed therapy including PARP inhibitors and immunotherapy. Response and treatment durations were reported, and BRCA1/2 dominated actionable findings.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Background

Materials and methods

Results

Prevalence of actionable PGV

Germline-directed therapies and clinical outcomes

Conclusions

Introduction

Historical criteria and objectives

Evolution toward therapeutic testing

Key words

ORIGINAL RESEARCH Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world S. W. Cheo1, P. Y. Ong1, S. G. W. Ow1, G. H. J. Chan1, D. S. P. Tan1, 2, 3, 4, Y. W. Lim1, H. L. Kong5, A. L. A. Wong1, S. E. Lim1, R. J. Walsh1, A. S. C. Wong1, J. J. H. Low6, N. Y. L. Ngoi1, J. S. L. Lim1, 2 , 3 & S. C. Lee1, 2, 3 􀀁 1Department of Haematology-Oncology, National University Cancer Institute, Singapore; 2Cancer Science Institute, National University of Singapore, Singapore; 3Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 4NUS Centre for Cancer Research (N2CR), National University of Singapore, Singapore; 5Icon Cancer Center, Singapore; 6Department of Obstetrics and Gynaecology, National University Hospital, Singapore Available online xxx Background: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications. Materials and methods: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. Results: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35 .6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62 .3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19 .7%) . One hundred and ﬁfty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors ¼ 75; immunotherapy ¼ 4) . Median duration of immunotherapy and poly ADP ribose polymerase were 20 .5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53%(n ¼ 17 breast cancers) and objective response rate was >80% in the advanced setting (n ¼ 71) . Conclusions: One-third of cancer patients tested carried a PGV and w80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics. Key words: therapeutic applications, germline testing, cancer predisposition genes, pathogenic germline variants, precision oncology, BRCA INTRODUCTION Historically, guidelines have recommended germline genetic testing for cancer predisposition genes in selected populations with signiﬁcant risk of harbouring pathogenic germline variants (PGV) .1 Conventional criteria for germline genetic testing include personal/family history of related cancers, personal history of young-onset cancer, or multiple primary cancers.2 The traditional objectives of germline genetic testing were to identify high-risk individuals who may beneﬁt from enhanced cancer surveillance and/or preventive strategies.3-5 The reasons for this targeted *Correspondence to: Prof. Soo Chin Lee, Department of HaematologyOncology, National University Cancer Institute, 1E Kent Ridge Road, Singapore 119228. Tel: þ65-6908-2222 E-mail: [csilsc@nus.edu.sg](csilsc@nus.edu.sg) (S. C. Lee). 2059-7029/© 2024 The Author(s). Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). approach were largely due to the cost of testing and the lack of therapeutic actionability of genetic testing in the past.1 Over the years, the criteria and methods of genetic test

FAQs

What is the main purpose of germline genetic testing discussed in the document?

The document explains that germline testing has traditionally supported cancer surveillance and prevention in suspected hereditary syndromes, and is increasingly used for therapeutic decision-making.

How many patients carried actionable pathogenic germline variants (PGV)?

Among 1154 tested cancer patients, 411 (35.6%) harboured a PGV, and 334 (81%) of those PGVs were clinically actionable.

What types of germline-directed therapies were used for advanced cancers?

In germline-positive advanced cancer patients, 79 received germline-directed therapies, primarily PARP inhibitors (75 cases) and also immunotherapy (4 cases).

Sep 21, 2026

Uploaded by Hazel