scholarly journals MP09-08 HIGH RATES OF METASTATIC DISEASE IN PROSTATE CANCER AMONG BRCA2 MUTATION CARRIERS: IMPLICATIONS FOR SCREENING

2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
Stephanie Gleicher ◽  
Eric Kauffman ◽  
Gennady Bratslavsky ◽  
Srinivas Vourganti
2014 ◽  
Vol 8 (11-12) ◽  
pp. 783 ◽  
Author(s):  
Richard Walker ◽  
Alyssa Louis ◽  
Alejandro Berlin ◽  
Sheri Horsburgh ◽  
Robert G. Bristow ◽  
...  

Introduction: The prostate-specific antigen (PSA) era and resultant early detection of prostate cancer has presented clinicians with the challenge of distinguishing indolent from aggressive tumours. Mutations in the BRCA1/2 genes have been associated with prostate cancer risk and prognosis. We describe the prostate cancer screening characteristics of BRCA1/2 mutation carriers, who may be classified as genetically-defined high risk, as compared to another high-risk cohort of men with a family history of prostate cancer to evaluate the utility of a targeted screening approach for these men.Methods: We reviewed patient demographics, clinical screening characteristics, pathological features, and treatment outcomes between a group of BRCA1 or BRCA2 mutation carriers and age-matched men with a family history of prostate cancer followed at our institutional Prostate Cancer Prevention Clinic from 1995 to 2012.Results: Screening characteristics were similar between the mutation carriers (n = 53) and the family history group (n = 53). Some cancers would be missed in both groups by using a PSA cut-off of >4 ug/L. While cancer detection was higher in the family history group (21% vs. 15%), the mutation carrier group was more likely to have intermediate- or high-risk disease (88% vs. 36%). BRCA2 mutation carriers were more likely to have aggressive disease, biological recurrence, and distant metastasis.Conclusions: In our cohort, regular screening appears justified for detecting prostate cancer in BRCA1 and BRCA2 carriers and other high-risk populations. Lowering PSA cut-offs and defining monitoring of PSA velocity as part of the screening protocol may be useful. BRCA2 is associated with more aggressive disease, while the outcome for BRCA1 mutation carriers requires further study. Large multinational studies will be important to define screening techniques for this unique high-risk population.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 8-8
Author(s):  
Christos Mikropoulos ◽  
Elena Castro ◽  
Elizabeth Bancroft ◽  
Elizabeth Page ◽  
Natalie Taylor ◽  
...  

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.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4653-4653
Author(s):  
Emma Killick ◽  
Richard Morgan ◽  
Francesca Launchbury ◽  
Nicola E. Annels ◽  
Elizabeth Bancroft ◽  
...  

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.


2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
Christina Selkirk ◽  
David Hatcher ◽  
Jacquelyn Powers ◽  
Peter Hulick ◽  
Michael McGuire ◽  
...  

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