Rapid progression of prostate cancer in men with a BRCA2 mutation

Abstract

Men with BRCA2 mutations have been found to be at increased risk of developing prostate cancer. There is a recent report that BRCA2 carriers with prostate cancer have poorer survival than noncarrier prostate cancer patients. In this study, we compared survival of men with a BRCA2 mutation and prostate cancer with that of men with a BRCA1 mutation and prostate cancer. We obtained the age at diagnosis, age at death or current age from 182 men with prostate cancer from families with a BRCA2 mutation and from 119 men with prostate cancer from families with a BRCA1 mutation. The median survival from diagnosis was 4.0 years for men with a BRCA2 mutation vs 8.0 years for men with a BRCA1 mutation, and the difference was highly significant (Po0.01). It may be important to develop targeted chemotherapies to treat prostate cancer in men with a BRCA2 mutation. British Journal of Cancer (2008) BRCA2 is a multisite cancer gene. It is generally thought that BRCA2 mutations primarily affect women, but men with mutations are also at elevated cancer risk. The two most important cancer sites for males who carry a mutation are the prostate and the pancreas (Liede et al, 2004). The risk of prostate cancer is elevated approximately fivefold in BRCA2 carriers, compared to noncarriers. Genetic counselors and urologists advise men with BRCA2 mutations to undergo surveillance with annual PSA testing from the age of 40 years -a recommendation based on the perceived effectiveness of prostate screening. It is hoped that screening leads to early diagnosis, when cure rates are high. A recent study from Iceland suggests that prostate cancers in men with a BRCA2 mutation may be unusually aggressive (Tryggvadottir et al, 2007). Tryggvadottir et al (2007) identified the Icelandic founder mutation (BRCA2 999 del5) in 30 of the 527 prostate cancer patients studied (5.7%). Men with a BRCA2 mutation had a median survival of only 2.1 years, compared with 12.4 years for noncarriers (Po0.01). The survival difference could not be explained by stage or grade. It is important that these findings be replicated because of the implications for the screening of men with a BRCA2 mutation. We identified the prostate cancer patients in a panel of 2673 families with a BRCA1 or a BRCA2 mutation and estimated survival of the men in the two subgroups. METHODSMen with prostate cancer were included in the survival analysis if they were from a family with a BRCA mutation and if they were (a) known to carry the familial BRCA mutation, or (b) if they were a first-degree relative of a known carrier, or (c) if they were a firstdegree relative of a woman diagnosed with breast or ovarian cancer. For each eligible man with prostate cancer, information was collected on age at diagnosis, age at death (if deceased) or age when last known alive (if alive). Information was collected by the

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

“…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.…”

The role of BRCA1 and BRCA2 in prostate cancer

“…Narod et al 90 reported a series of 67 BRCA2 and 37 BRCA1 mutation carriers or obligate carriers of different BRCA mutations. The study analysed the prognosis of BRCA1 vs. BRCA2 mutation carriers and did not include a BRCA wild-type group for comparison.…”

The therapeutic ratio is preserved for radiotherapy or cisplatin treatment in BRCA2-mutated prostate cancers

“…[3][4][5] BRCA2 is a tumour suppressor protein involved in the repair of DNA double-strand breaks via homologous recombination (HR). Tumour tissues derived from BRCA2 mutation carriers (e.g., male or female breast cancers, ovarian cancer and prostate cancer being the most common) may respond differently to radiotherapy (RT) and chemotherapy when compared to tumours with normal BRCA2 and HR protein function.…”