Purpose Increased prostate cancer risk has been reported for BRCA mutation carriers but BRCA-associated clinicopathologic features have not been clearly defined. Experimental Design We determined BRCA mutation prevalence in 832 Ashkenazi Jewish (AJ) men diagnosed with localized prostate cancer between 1988 and 2007 and 454 AJ controls, and compared clinical outcome measures among 26 BRCA mutation carriers and 806 non-carriers. Kruskal-Wallis tests were used to compare age of diagnosis and Gleason Score (GS), and logistic regression models to determine associations between carrier status, prostate cancer risk, and GS. Hazard ratios for clinical endpoints were estimated using Cox proportional hazards models. Results BRCA2 mutations were associated with a threefold risk of prostate cancer (OR [95% CI]=3.18 [1.52-6.66]; p = 0.002), and presented with more poorly differentiated (GS ≥ 7) tumors(85% vs. 57%, p= 0.0002) compared with non-BRCA associated PC. BRCA1 mutations conferred no increased risk. After 7,254 person-years of follow-up, and adjusting for clinical stage, PSA, GS, and treatment, BRCA2 and BRCA1 mutation carriers had a higher risk of recurrence (HR [95% CI] = 2.41[1.23, 4.75] and 4.32 [1.31, 13.62], respectively) and prostate cancer -specific death (HR [95% CI] = 5.48 [2.03, 14.79] and 5.16 [1.09,24.53], respectively) than non-carriers. Conclusions BRCA2 mutation-carriers had an increased risk of prostate cancer and a higher histological grade, and BRCA1 or BRCA2 mutations were associated with a more aggressive clinical course. These results may have impact on tailoring clinical management of this subset of hereditary prostate cancer.

Wissen, worauf es ankommt: Das einfachste Photosyntheseprotein, das Sonnenlicht in andere Energieformen umwandelt, wurde kovalent mit einem maßgeschneiderten organischen Farbstoff verknüpft, um einen voll funktionsfähigen Hybridkomplex zu erhalten, der das natürliche System hinsichtlich der Lichtsammlung und ‐umwandlung übertrifft.

BACKGROUND Multiple observational studies have suggested that BRCA-associated ovarian cancers have improved survival compared to BRCA-negative ovarian cancers. Most of these studies, however, have combined BRCA1 and BRCA2 patients or evaluated only BRCA1 patients. We sought to examine if BRCA1− and BRCA2-associated ovarian cancers were associated with different outcomes. METHODS A single-institution retrospective analysis of patients seen between January 1, 1996 and February 1st, 2011 for a new diagnosis of histologically confirmed Stage III or IV serous ovarian, fallopian tube, or primary peritoneal cancer and who underwent BRCA mutation testing on one of two IRB approved follow-up studies. Patients tested for BRCA mutations beyond 24 months of diagnosis were excluded from analysis to minimize selection bias from including patients referred for genetic testing because of long survival. RESULTS Data from 190 patients (143 BRCA−, 30 BRCA1+, 17 BRCA2+) were analyzed. During the study period, 73 deaths were observed (60 BRCA−, 10 BRCA1+, 3 BRCA2+). Median follow-up time for the remaining 117 survivors was 2.5 years. At 3 years, 69.4%, 90·7%, and 100% of BRCA−, BRCA1+, and BRCA2+ patients were alive, respectively. On univariate analysis, age, BRCA2, debulking status, and type of first-line therapy (intravenous or intraperitoneal) were significant predictors of overall survival (OS). On multivariate analysis, BRCA2 status (HR .20; 95% CI, .06–.65; P=.007) but not BRCA1 status (HR .70; 95% CI, .36–1.38; P=.31) predicted for improved OS compared to BRCA-patients. When carriers of BRCA2 mutations were directly compared to carriers of BRCA1 mutations, BRCA2 mutation status appeared to confer an improved OS (HR .29; 95% CI, 0.08–1.05; P=.060), although this finding did not reach significance. CONCLUSION Our data suggest that BRCA2 status confers an overall survival advantage compared to both BRCA− and BRCA1 status in high-grade serous ovarian cancer. This finding may have important implications for clinic trial design.

BRCA mutation status predicted OS independent of primary platinum sensitivity, suggesting that underlying tumor biology contributes to disease outcome and may be worthy of consideration in future clinical trial design.

IntroductionPrevious studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour.MethodsWe used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach.ResultsThe results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status.ConclusionsThe associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.