Decreased Prostate Cancer-Specific Survival of Men with BRCA2 Mutations from Multiple Breast Cancer Families

Abstract

The role of a germ-line BRCA2 mutation in the development of prostate cancer is established, but the clinical presentation linked to outcome for this group of men has not been well described.A total of 148 men from 1,423 families were ascertained from the kConFab consortium. Each participant met the following criteria: (i) a verified case of prostate cancer; (ii) confirmed as either a carrier or noncarrier of a family-specific BRCA pathogenic mutation; (iii) comprehensive clinical and treatment data were available. Clinical data were linked to treatment received and overall survival was analyzed by Kaplan-Meier.Prostate cancer in men from breast cancer-prone families has a high risk of disease progression, irrespective of mutation status. BRCA2 mutation carriers have an increased risk of death and prostate cancer-related death [HR (95% CI) 4.5 (2.12-9.52), P ¼ 8.9 Â 10 À5 ] by comparison with noncarriers. Serum PSA readings taken prior to diagnosis in 90% of all men, age adjusted, were above clinical significance. Following D'Amico risk stratification, 77.5% of BRCA2 mutation carriers and 58.7% of noncarriers had high-risk disease. BRCA2 mutation status was also an independent prognostic indicator of overall survival. Furthermore, there was a poor overall survival outcome for both the BRCA2 mutation carriers and noncarriers given curative-intent treatment.All men in breast cancer-prone families are at risk of developing aggressive prostate cancer. This information is significant and should be included in discussions with genetic counselors and medical professionals when discussing prostate cancer treatment options for men in these families, irrespective of mutation status.

The role of BRCA1 and BRCA2 in prostate cancer

“…We have not seen differences in age at diagnosis as previously reported by others. 65,84,89,91 This contradicts Tryggvadottir's observations, 64 but our study 63 did not include any patients with the Icelandic founder mutation BRCA2 999del5, and we cannot exclude that some mutations are associated with younger age at diagnosis. BRCA1 and BRCA2 carriers had a higher incidence of poorly differentiated tumours, presented with larger tumours and a higher incidence of node involvement and distant metastasis.…”

“…Carriers had a median OS of only 4.8 years compared with 8.5 years for the noncarriers. More recently, Thorne et al 89 reported the analysis of the outcome of PCa in 40 BRCA2 mutation carriers compared with 97 BRCA wild-type patients. Non-carriers belonged to families with a history of breast cancer.…”

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

“…There remains debate about whether there is an increased risk of PrCa associated with BRCA1 mutations, with some studies reporting no increased risk to those reporting a 1.8-3.75 fold increased risk (Thompson et al, 2002;Leongamornlert et al, 2012;Moran et al, 2012). A number of studies have reported that BRCA2 mutation carriers have more aggressive disease, suggested by their younger age at diagnosis, higher rates of lymph node involvement and distant metastasis at diagnosis, and higher mortality rates compared with non-carriers (Tryggvadóttir et al, 2007;Mitra et al, 2008;Edwards et al, 2010;Gallagher et al, 2010;Thorne et al, 2011;Castro et al, 2013). There is increasing evidence that BRCA1 mutation carriers may also harbour more aggressive disease (Giusti et al, 2003;Gallagher et al, 2010;Castro et al, 2013).…”

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

“…12 Other similar studies corroborate these findings. [13][14][15][16] Until recently, reports on the screening outcomes of male BRCA1/2 carriers have been scarce and often limited to specific founder mutations studied in a select population. In 2005, our centre evaluated the utility of targeted screening for detecting prostate cancer in BRCA1/2 carriers.…”

“…[11][12][13][14][15][16][21][22][23][24] This study sought to understand the screening characteristics, cancer detection, and treatment outcomes for mutation carriers as compared to men with a family history of prostate cancer to understand the most appropriate screening and treatment regimens for these high-risk patients.…”