%0 Journal Article
%T Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world.
%A Cheo SW
%A Ong PY
%A Ow SGW
%A Chan GHJ
%A Tan DSP
%A Lim YW
%A Kong HL
%A Wong ALA
%A Lim SE
%A Walsh RJ
%A Wong ASC
%A Low JJH
%A Ngoi NYL
%A Lim JSL
%A Lee SC
%J ESMO Open
%V 9
%N 6
%D 2024 Jun 3
%M 38833967
%F 6.883
%R 10.1016/j.esmoop.2024.103482
%X <B>BACKGROUND: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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 = 75; immunotherapy = 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 = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71).<BR><B>CONCLUSIONS: </B>One-third of cancer patients tested carried a PGV and ∼80% 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.