Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer

Castro, Elena; Goh, Chee; Leongamornlert, Daniel; Saunders, Ed; Tymrakiewicz, Malgorzata; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Ellis, Steve; Frost, Debra; Bancroft, Elizabeth; Cole, Trevor; Tischkowitz, Marc; Kennedy, Michael J.; Eason, Jacqueline; Brewer, Carole; Evans, D. Gareth; Davidson, Rosemarie; Eccles, Diana; Porteous, Mary; Douglas, Fiona; Adlard, Julian; Donaldson, Alan; Antoniou, Antonis C.; Kóte-Jarai, Zsofia; Easton, Douglas F.; Olmos, David; Eeles, Rosalind

doi:10.1016/j.eururo.2014.10.022

Cited by 301 publications

(241 citation statements)

References 25 publications

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“…However, there were no differences in median PSAV between carriers and noncarriers. Given the possibility that higher PSAV may associate with aggressive PrCa (D'Amico et al, 2004; D'Amico et al, 2005), we would expect BRCA2 carriers who are at risk of aggressive disease would exhibit higher PSAVs (Castro et al, 2013;Castro et al, 2015). BRCA2 carriers in this group may be too young to demonstrate this trend at this point of follow up.…”

Section: Discussionmentioning

confidence: 83%

“…This may help delineate PSAV among men diagnosed with PrCa with low PSA values (Carter et al, 1992; Kitagawa et al, 2014). A strength of this study is the unique patient cohort of men with a genetic predisposition to PrCa, in particular BRCA2 carriers who are predisposed to aggressive PrCas (Mitra et al, 2008;Narod et al, 2008;Castro et al, 2013;Castro et al, 2015). Within the group of BRCA2 carriers, PSAV proved predictive of any grade cancer, however, given the low number of cancers diagnosed overall it was not possible to assess whether PSAV was associated with high grade cancer and BRCA2 status.…”

Section: Discussionmentioning

confidence: 99%

“…However, early diagnosis and identification of men with high-risk disease is important to prevent mortality from PrCa. This might be particularly essential in light of recent publications indicating that men with a BRCA1 or BRCA2 mutation are at risk of more aggressive disease (Castro et al, 2013;Castro et al, 2015), early identification of those with clinically significant disease will be imperative. In view of the controversy about the role of PSAV in prostate screening in the general population, it was important to assess its role in BRCA1 and BRCA2 carriers and whether it added to the ability to detect clinically significant disease.…”

Section: Discussionmentioning

confidence: 99%

“…It may lead to better prognosis for men at risk for more aggressive disease and better disease-free survival when treated early. Although there are no definitive treatment recommendations for men with BRCA2 mutations when found to be diagnosed with low grade cancers, their risk for aggressive disease may spur them to follow a more active treatment plan such as radical prostatectomy vs external-beam radiation therapy or active surveillance (Bratt and Loman, 2015;Castro et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Erratum: Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

Mikropoulos¹,

Selkirk²,

Saya³

et al. 2018

Br J Cancer

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Erratum: Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

Mikropoulos¹,

Selkirk²,

Saya³

et al. 2018

Br J Cancer

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“…About 9% of men with PCa have truly hereditary disease, which is associated with an onset six to seven years earlier than spontaneous cases, but the biology does not differ. The only exception are carriers of the rare BRCA2 germline abnormality, who seem to have an increased risk of early-onset PCa with aggressive behaviour [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

et al. 2017

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Prevalence of Germline Variants in Prostate Cancer and Implications for Current Genetic Testing Guidelines

et al. 2019

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IMPORTANCE Prostate cancer is the third leading cause of cancer-related death in men in the United States. Although serious, most of these diagnoses are not terminal. Inherited risk for prostate cancer is associated with aggressive disease and poorer outcomes, indicating a critical need for increased genetic screening to identify disease-causing variants that can pinpoint individuals at increased risk for metastatic castration-resistant prostate cancer.OBJECTIVE To identify positive (pathogenic, likely pathogenic, and increased risk) germline variants in a large prostate cancer cohort and to evaluate the usefulness of current practice guidelines in recognizing individuals at increased risk for prostate cancer who would benefit from diagnostic genetic testing. DESIGN, SETTING, AND PARTICIPANTSCross-sectional study of data from 3607 men with a personal history of prostate cancer who underwent germline genetic testing between 2013 and 2018 and were unselected for family history, stage of disease, or age at diagnosis. Referral-based testing was performed at a Clinical Laboratory Improvement Amendments/College of American Pathologists-certified diagnostic laboratory. All analysis took place between February 2017 and August 2018. MAIN OUTCOMES AND MEASURESThe frequency and distribution of positive germline variants, and the percentage of individuals with prostate cancer who met National Comprehensive Cancer Network (NCCN) guidelines for germline genetic testing. RESULTSOf 3607 men (mean [SD] age at testing, 67 [9.51] years; mean age at diagnosis, 60 [9.05] years) with a personal diagnosis of prostate cancer who were referred for genetic testing, 620 (17.2%) had positive germline variants, of which only 30.7% were variants in BRCA1/2. Positive variants in HOXB13, a gene associated only with prostate cancer risk, were identified in 30 patients (4.5%). DNA mismatch repair variants with substantial known therapeutic implications were detected in 1.74% of variants in the total population tested. Examination of self-reported family histories indicated that 229 individuals (37%) with positive variants in this cohort would not have been approved for genetic testing using the NCCN genetic/familial breast and ovarian guidelines for patients with prostate cancer. CONCLUSIONS AND RELEVANCECurrent NCCN guidelines and Gleason scores cannot reliably stratify patients with prostate cancer for the presence or absence of pathogenic germline variants. Most positive genetic test results identified in this study have important management implications for patients and their families, which underscores the need to revisit current guidelines.

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Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer

Cited by 301 publications

References 25 publications

Erratum: Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

Erratum: Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

Prevalence of Germline Variants in Prostate Cancer and Implications for Current Genetic Testing Guidelines

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