IDENTIFICATION OF MEN WITH A GENETIC PREDISPOSITION TO PROSTATE CANCER: TARGETED SCREENING OF BRCA1 AND BRCA2 MUTATION CARRIERS AND CONTROLS THE IMPACT STUDY PILOT RESULTS

2009 ◽  
Vol 181 (4) ◽  
pp. 644
Author(s):  
Wendy S Rubinstein ◽  
Christina G Selkirk ◽  
Cherese Pullum ◽  
Karen L Kaul ◽  
Charles B Brendler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Predisposition ◽  
Brca2 Mutation ◽  
Impact Study ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Targeted Screening ◽  
The Impact

scholarly journals Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

2014 ◽  
Vol 66 (3) ◽  
pp. 489-499 ◽  
Author(s):  
Elizabeth K. Bancroft ◽  
Elizabeth C. Page ◽  
Elena Castro ◽  
Hans Lilja ◽  
Andrew Vickers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Screening ◽  
Prostate Cancer Screening ◽  
Brca2 Mutation ◽  
Impact Study ◽  
Initial Screening ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
The Impact

Detecting prostate cancer in BRCA1 and BRCA2 mutation carriers: A role for EN2?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4653-4653
Author(s):  
Emma Killick ◽  
Richard Morgan ◽  
Francesca Launchbury ◽  
Nicola E. Annels ◽  
Elizabeth Bancroft ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Group ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Digital Rectal Examination ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers ◽  
The Impact

4653 Background: EN2 is part of the HOX gene family and plays a role in foetal development. More recently a potential oncogenic role for the protein has been postulated and its utility as a cancer biomarker has been explored in prostate cancer (PrCa) and breast cancer. Carriers of mutations in the BRCA1 and BRCA2 genes have an increased risk of PrCa (1.8-fold and 5-fold respectively) and their tumours tend to be more aggressive and advanced than sporadic cases. Currently there is no national screening program for BRCA mutation carriers in the UK, and the IMPACT study was set up to evaluate PSA screening in this particular group. Here we analyse the efficacy of the urinary EN2 protein as a marker of early cancer detection within this higher risk group. Methods: First pass urine (without preceding digital rectal examination) was collected as part of the IMPACT screening study which enrolled individuals aged between 40 and 69 who were unaffected by PrCa at time of enrolment into the study (n= 418). All participants were from families harbouring a BRCA1 or BRCA2 mutation and were either BRCA mutation carriers themselves or controls with a negative predictive BRCA genetic test. They underwent annual PSA test with a PSA of > 3.0 ng/ml triggering a diagnostic biopsy. EN2 protein was measured in the urine using an ELISA; (positive = > 42.5ng/ml). Results: Our initial results demonstrated urinary EN2 had a sensitivity of 66.67% and a specificity of 89.29% when discriminating which men had been diagnosed with PrCa; the ROC AUC was 0.816. The difference in EN2 level between those diagnosed with cancer and those who were not was significant (p = <0.001). There was trend towards higher EN2 levels in those with more aggressive tumours (median EN2 84.5ng/mL in Gleason ≤3+4 vs 111ng/mL in Gleason ≥4+3), however this was not statistically significant. In one PrCa case EN2 rise preceded PSA rise by 2 years. Further samples are in the process of being analysed, results from these will be included. Conclusions: Urinary EN2 protein measurement warrants further investigation as a PrCa biomarker in this higher risk group with genetic predisposition to PrCa.

Prostate-specific antigen velocity as a predictive biomarker in a prospective prostate cancer screening study (IMPACT study).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 16-16
Author(s):  
Christos Mikropoulos ◽  
Christina Selkirk ◽  
Sibel Saya ◽  
Elizabeth Bancroft ◽  
Tokhir Dadaev ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Linear Regression ◽  
Genetic Predisposition ◽  
Brca2 Mutation ◽  
Specific Antigen ◽  
Impact Study ◽  
Screening Study ◽  
Brca1 Carriers ◽  
Clinically Significant ◽  
Negative Controls

16 Background: We retrospectively assessed the clinical application of Prostate Specific Antigen Velocity (PSA V) in the IMPACT study (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in men at higher genetic risk and controls). This is a case-control prostate cancer (PrCa) screening study for men with a known genetic predisposition to PrCa; participants with a single PSA reading above 3ng/ml are offered diagnostic TRUS prostate biopsies (PB). Methods: We calculated PSA velocity (PSA V) using all three validated methods, including the arithmetic mean, the linear regression and the first and last readings equations. Pearson chi-square test was used to compare PSA V between four genetic groups: BRCA1 carriers and BRCA1 negative controls and BRCA2 carriers and BRCA2 negative controls. Results: PSA V data were evaluated in 191 men who underwent a PB with a total of 57 PrCas diagnosed. PSA V using both a threshold of 0ng/ml/year and 0.75ng/ml/year in any of the three methods was not predictive of PrCa diagnosis in BRCA1/2 controls and BRCA1 carriers. Conversely, BRCA2 carriers with a PSA V over 0.75ng/ml/year (by linear regression) were 5 times more likely to be diagnosed with PrCa [95%CI=1.5-14; p=0.003]. Interestingly PSA V using linear regression was predictive of clinically significant tumours as defined by Gleason Score (GS) >= 7. Regardless of their genetic status, men with a PSA V over 0.75/ng/ml/year were 3 times more likely to have a clinically significant PrCa [95% CI: 1.006-11.107; p=0.045] whereas men with a BRCA2 mutation were 12 times more likely [95%CI: 1.1-98; p=0.039]. Conclusions: PSA V is an important tool for identifying which men with a BRCA2 mutation would benefit from a prostatic biopsy and could be incorporated into a predictive model, along with the total PSA value. PSA V also predicts for tumour aggressiveness regardless of genetic predisposition, but more so for those with a known high risk gene mutation. Clinical trial information: NCT00261456.

Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers to detect clinically significant disease: Results from the initial screening round of the IMPACT study.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 8-8
Author(s):  
Christos Mikropoulos ◽  
Elena Castro ◽  
Elizabeth Bancroft ◽  
Elizabeth Page ◽  
Natalie Taylor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Brca2 Mutation ◽  
Psa Testing ◽  
Mutation Carriers ◽  
High Risk Disease ◽  
Brca1 Carriers ◽  
Clinically Significant ◽  
The Impact ◽  
Significant Disease

8 Background: Men with germline BRCA1/2 mutations have a higher risk of developing prostate cancer (PrCa) than non-carriers. IMPACT is an international consortium of 62 centers in 20 countries evaluating the use of targeted PrCa screening in men with BRCA1/2 mutations. This analysis reports the first year’s screening results for all men at enrolment in the study. Methods: We recruited men aged between age 40 and 69 with germline BRCA1/2 mutations and a control group that tested negative for a BRCA1/2 mutation. All men underwent prostate-specific antigen (PSA) testing at enrollment and those with a PSA of greater than 3ng/ml threshold were offered prostate biopsy. All men are offered a biopsy irrespective of PSA level after five years of screening. Results: We recruited 2,481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls) of whom 199 (8%) presented with a PSA greater than 3ng/ml. We performed a total of 162 biopsies and diagnosed 59 PrCas (18 BRCA1 carriers, ten BRCA1 controls; 24 BRCA2 carriers, seven BRCA2 controls); 66% of the tumors were classified as intermediate or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3·0ng/ml in BRCA2 mutation carriers was 48%, double that reported in population screening studies. A significant difference in detecting intermediate or high-risk disease was observed in BRCA2 carriers using this threshold. Conclusions: The IMPACT screening network will be useful for targeted PrCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this yields a high proportion of aggressive disease. Early data indicate that the majority of BRCA1/2 mutation carriers diagnosed with prostate cancer at biopsy had developed clinically significant disease (requiring radical treatment). Clinical trial information: NCT00261456.

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