Session: MP44: Prostate Cancer: Detection & Screening II
MP44-20: Male-Carriers of Gene Mutations associated with increased risk of Prostate Cancer: Results from a Single Institution Genetic Counseling Consultation
Introduction: Current international guidelines address genetic counseling for patients with Prostate Cancer (PCa) and family history and/or metastatic PCa (mPCa). We aimed to analyze results from males evaluated at our Family Cancer and Genetic Counseling Unit. Methods: Between 07-2020 and 09-2022, 1472 patients were counseled for genetic testing, of whom 318 (21,6%) were men. Male patients referred by urologists had at least one criteria of: (a) mutation carrier family member, (b) mPCa, (c) PCa and family history of mPCa, (d) high risk PCa <60y and family history of PCa, and (e) PCa <60y and family history of breast or ovarian cancer at <50y. Identified mutations on tested males were recorded as pathogenic, variants of uncertain significance or negative. We analyzed patient and disease characteristics on pathogenic carriers. We reviewed management recommendations of male healthy carriers. Results: Eighty-nine (28%) males had a pathogenic mutation on genetic testing. Fifthy-Five (17%) were related to PCa genetic counseling. We divided carriers into two groups: Group A (healthy carriers) and Group B (oncologic patients with identified pathogenic mutation). Group A (28/55; 51%) were tested due to known family mutation on close blood relatives. Family history was breast cancer in 24 (86%), PCa in 9 (32%), and HOBC in 6 (21%) HBOC. Median age was 41 (range 15-70), and pathogenic mutations were: 4 ATM, 7 BRCA1, 9 BRCA2, 1 MLH1, 2 MUTHY, 5 RAD51D and 1 TP53. Mean PSA was 1,02ng/dl (range 0,32-3,96). All group A patients had follow-up scheduled in Urology Genetic Counseling clinic and General Surgery Breast and Pancreas Cancer Unit. Healthy carriers had adapted PCa screening. Group B (27/55; 49%) patients had cancer: 16 (59%) had PCa, 7 (26%) Colorectal cancer and 4 (15%) other cancers. Median age was 52 (range 39-80). Family history of PCa was present in 13 (48%). Germline pathogenic mutations were found in 25 (93%): 4 ATM, 5 BRCA1, 4 BRCA2, 1 HOXB13, 2 MLH1, 1 MSH2, 1 MUTYH, 3 PALB2, 1 PMS2, 2 RAD51D and 2 TP53. Two patients (7%) had somatic pathogenic mutations. Out of the 16 patients with PCa, 37,5% had mPCa, 31,3% high risk PCa and 31,3% had intermediate risk PCa diagnosed at age <50y and >2 relatives with PCa. Somatic mutations were identified on mPCa. Conclusions: We found 28% of positive genetic testing in males. Patients with identified pathogenic variants should be recommended close follow-up as some are associated with aggressive PCa. The widespread use of genetic testing in other malignancies (i.e. Breast Cancer, HOBC), will increase healthy carriers. SOURCE OF Funding: -
