title: 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 = 8.9 × 10(-5)] 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.
authors: kConFab, Research Department, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia, 3002. heather.thorne@petermac.org.
authors: Heather
authors: H
authors: Thorne
authors: Amber J
authors: AJ
authors: Willems
authors: Eveline
authors: E
authors: Niedermayr
authors: Ivan M Y
authors: IM
authors: Hoh
authors: Jason
authors: J
authors: Li
authors: David
authors: D
authors: Clouston
authors: Gillian
authors: G
authors: Mitchell
authors: Stephen
authors: S
authors: Fox
authors: John L
authors: JL
authors: Hopper
authors: Damien
authors: D
authors: Bolton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000150:complications* / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000401:mortality* / Q000628:therapy; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human