Abstract 1818: Identification of men with a genetic predisposition to prostate cancer: Targeted screening of BRCA1/2 mutation carriers and controls; The IMPACT study

Abstract

Abstract Introduction: Men with a mutation in either the BRCA1 or BRCA2 gene have an increased risk of prostate cancer, estimated as 3-5% for BRCA1 and up to 20% for BRCA2 by age 70. It has been demonstrated that men with BRCA2 develop aggressive disease but the real incidence and prevalence of cancer in mutation carriers remains unknown. IMPACT is a multi-national targeted prostate cancer screening study of men with a known germline mutation which is thought to predispose to the disease. The study is recruiting male BRCA1/2 mutation carriers and a control group who have tested negative for a mutation present in their family from 37 centres in 14 countries. The aims of the study are to establish an international targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers; to determine the sensitivity and specificity of PSA screening for prostate cancer in this group; to determine the incidence of abnormal biopsy as a result of PSA screening in this group and to determine whether the pathology of tumours is different from screen-detected disease in controls. Method: Eligible men aged 40-69 years are offered annual serum PSA testing for five years. The PSA threshold used to determine prostate biopsy is >3ng/ml. All men are offered a biopsy irrespective of PSA level after 5 years of screening. Men are also invited to take part in a Quality of Life sub-study. Results: To date 1000/1700 men have been recruited, 77 have undergone biopsy and 30 men have been diagnosed with prostate cancer (18 BRCA2 carriers, 7 BRCA1 carriers and 5 controls). 80% of cases diagnosed in BRCA1/2 carriers were Gleason score ≥7 and T2 or higher (in the intermediate/high risk group for immediate radical treatment and not active surveillance, according to NICE guidelines) while in the general population (ERSPC study), 72% had a Gleason ≤6 and 61% were T1 (low risk group, suitable for active surveillance). The estimated positive predictive value for PSA screening in BRCA carriers is 44% vs 24% in the general population (ERSPC study). Conclusions: Our preliminary results show that annual PSA screening using a cut-off of 3.0ng/ml detects aggressive prostate cancer in BRCA1/2 carriers. The higher risk of PrCa observed in BRCA1 and BRCA2 carriers will need to be confirmed with further data. Early data indicate that a larger proportion of gene carriers have developed clinically significant prostate cancers (those that would need radical treatment on UK treatment guidelines) compared with the control group. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1818. doi:10.1158/1538-7445.AM2011-1818