Prostate cancer screening characteristics in men with BRCA1/2 mutations attending a high-risk prevention clinic

Abstract

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 agematched 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.

Implications of High Rates of Metastatic Prostate Cancer inBRCA2Mutation Carriers

“…The MEDLINE database query resulted in 289 studies, of which 12 met inclusion criteria (Table ). Mitra et al consisted of preliminary findings that were later reported in the Bancroft et al study, so it was not included in the analysis .…”

“…The data extracted from each study included year of publication, study type, population of interest, identified mutations, age, PSA level, GS, tumor stage, and outcomes data of overall and cause‐specific survival. Tumor stage was determined by clinical and surgical findings. Chi‐squared statistics and P ‐values were calculated to compare GS and stage among retrospective and prospective studies , as well as by average age groupings (<65 vs. >65 years ).…”

“…Associated with hereditary breast and ovarian cancer (HBOC), approximately 1.2% of prostate cancer cases among men less than 65 years of age and 6% of metastatic castration resistant prostate cancer (mCRPC) cases carry germline BRCA2 mut . Men who carry germline BRCA2 mut are up to eight times more likely to develop prostate cancer compared to non‐carriers, and develop an aggressive disease variant with advanced stage and grade at presentation and poor survival outcomes . These findings have been reflected in numerous studies comprised of small samples from disparate populations.…”

Tumor characterization by ultrasound-release of multiple protein and microRNA biomarkers, preclinical and clinical evidence

“…In the clinical environment of blood-based biomarker studies it has been shown that a single biomarker is generally not effective in detecting or guiding management and detection of disease, and that panels of multiple biomarkers are required [ 15 – 19 ]. Protein blood biomarkers such as carcinoembryonic antigen (CEA), cancer antigen 19–9 (CA19-9) and prostate specific antigen (PSA) used in this study, have been widely studied for many decades and are used in mainstream clinical disease management [ 20 – 24 ]. Endothelin-1, cancer antigen 125 (CA125) and cancer antigen 15–3 (CA15-3) have been studied in uterine fibroids [ 25 – 27 ].…”

Expressão da proteína BRCA2 em prostatectomia e sua correlação com a biópsia em pacientes com câncer de próstata

“…Um biomarcador é definido como uma molécula ou outro dado que caracteriza um processo biológico em estado normal e patológico, sendo que sua expressão se diferencia ou só é estabelecida em estado patológico. Logo, é uma ferramenta importante, utilizada para se Nossa hipótese a respeito do PSA, que ainda é um método de intensa controvérsia, pode ser sustentada pelo fato do PSA não ser considerado câncer específico, podendo estar alterado em outros processos patológicos da próstata, reforçando a ideia de que o aumento do PSA visto em tumores da próstata não esteja diretamente relacionado ao processo neoplásico, diminuindo a confiabilidade da utilização do PSA no diagnóstico prostático, fato que tem sido cada vez mais sugerido por estudiosos da área(56)(57)(58)(59)(60). Gleason =7, apresentaram expressão positiva para o marcador em questão.…”