{Reference Type}: Journal Article
{Title}: Therapeutic applications of germline testing for cancer predisposition genes in Asia in the real world.
{Author}: Cheo SW;Ong PY;Ow SGW;Chan GHJ;Tan DSP;Lim YW;Kong HL;Wong ALA;Lim SE;Walsh RJ;Wong ASC;Low JJH;Ngoi NYL;Lim JSL;Lee SC;
{Journal}: ESMO Open
{Volume}: 9
{Issue}: 6
{Year}: 2024 Jun 3
{Factor}: 6.883
{DOI}: 10.1016/j.esmoop.2024.103482
{Abstract}: <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.