Dataset Information

A population-based analysis of germline BRCA1 and BRCA2 testing among ovarian cancer patients in an era of histotype-specific approaches to ovarian cancer prevention.

ABSTRACT: Identifying female carriers of BRCA1 and BRCA2 mutations is imperative for prevention of ovarian cancer and breast cancer. There are five major histologic subtypes of ovarian cancer and high grade serous cancer (the most common) is reported in 75-100% of BRCA1 and BRCA2 mutation carriers. We examined histology-based referral to the Hereditary Cancer Program following an educational prevention campaign recommending BRCA1 and BRCA2 mutation screening for all high-grade serous cancer patients.We conducted a population-based retrospective study in the province of British Columbia, Canada that included all patients visiting the Hereditary Cancer Program for genetic counselling for BRCA1 and BRCA2 mutation between 2001 and 2014. We examined the difference in rates of BRCA1 and BRCA2 testing between serous cancer patients and endometrioid and clear cell cancer patients using a differences in differences analysis. We also calculated the mean number of family members tested for every BRCA1 and BRCA2 identified ovarian cancer patient before and after the educational campaign.There were 5712 women tested for a BRCA1 and BRCA2 mutation at the HCP between 2001 and 2014, 887 of which had previously received a diagnosis of ovarian cancer. By 2013, 43% of serous cancer patients were being tested for BRCA1 and BRCA2 mutations compared with 20% of endometrioid and clear cell patients (p < 0.001). The mean number of family members tested for each BRCA1 and BRCA2 positive ovarian cancer patient increased after the educational campaign from 2.54 to 3.27 (p = 0.071), and the number of family members identified as BRCA positive also increased significantly.Recommendations for histology-based referral significantly increased the likelihood of serous cancer patients being tested for BRCA mutations. There was also an increase in the number of carrier tests performed for each BRCA1 and BRCA2 index ovarian cancer patient.

SUBMITTER: Hanley GE

PROVIDER: S-EPMC5838948 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Aim of workReporting the incidence and the variants of BRCA1/2 mutations in ovarian cancer patients exploring their effects on the treatment outcomes.Patients and methodsIn total, 104 patients with epithelial ovarian cancer were prospectively recruited to the study. Analysis consisted of the sequencing of all the translated exons and immediately adjacent intronic regions of the BRCA1/2 genes. Responses to multiple lines of chemotherapy were assessed, as well as the effect of BRCA gene mutations on progression-free survival (PFS) and overall survival (OS).ResultsPathogenic BRCA1/2 mutations were found in 21.15% of the patients. BRCA1 mutations represented 68.2% of the total mutations. Two novel BRCA1 mutations were identified. Age at diagnosis was a strong predictor of the presence of a pathogenic BRCA1/2 mutation. Patients with a family history of cancer had a higher incidence of BRCA mutations (P=0.005). As high as 72% of the patients with BRCA mutations were diagnosed at advanced stage. High-grade serous tumors have a higher incidence of pathogenic mutation (P=0.07). Response to neoadjuvant chemotherapy was high (93.9%). All patients underwent surgery which was optimal in 73.1% of the patients. As high as 85.6% of the patients received adjuvant chemotherapy. Relapse rate was 45.2%. Visceral metastasis was more often in BRCA carriers (P=0.01). Patients carrying pathogenic BRCA1/2 mutations had a longer median PFS of 42.43 months (95% CI 32.04-52.83) compared to 22.24 months (95% CI 14.83-29.58) for non-carriers (P=0.08). OS was 64.32 months (95% CI 38.09-90.06) for BRCA mutation patients versus 56.63 months (95% CI 50.05-63.21) (P=0.04) for non-carriers. In multivariate analysis, early stage at diagnosis and optimal debulking were the only independent predictors of better PFS and OS.ConclusionWe documented a number of pathogenic BRCA1 and 2 mutations in this patients cohort; two novel mutations were detected. BRCA status seemed to affect survival in ovarian cancer patients.

Project description:BackgroundApproximately 3/4 of ovarian cancers are diagnosed in advanced stages, with the high-grade epithelial ovarian carcinoma (EOC) accounting for 90% of the cases. EOC present high genomic instability and somatic loss-of-function variants in genes associated with homologous recombination mutational repair pathway (HR), such as BRCA1 and BRCA2, and in TP53. The identification of germline variants in HR genes in EOC is relevant for treatment of platinum resistant tumors and relapsed tumors with therapies based in synthetic lethality such as PARP inhibitors. Patients with somatic variants in HR genes may also benefit from these therapies. In this work was analyzed the frequency of somatic variants in BRCA1, BRCA2, and TP53 in an EOC cohort of Brazilian patients, estimating the proportion of variants in tumoral tissue and their association with progression-free survival and overall survival.MethodsThe study was conducted with paired blood/tumor samples from 56 patients. Germline and tumoral sequences of BRCA1, BRCA2, and TP53 were obtained by massive parallel sequencing. The HaplotypeCaller method was used for calling germline variants, and somatic variants were called with Mutect2.ResultsA total of 26 germline variants were found, and seven patients presented germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2. The analysis of tumoral tissue identified 52 somatic variants in 41 patients, being 43 somatic variants affecting or likely affecting protein functionality. Survival analyses showed that tumor staging was associated with overall survival (OS), while the presence of somatic mutation in TP53 was not associated with OS or progression-free survival.ConclusionFrequency of pathogenic or likely pathogenic germline variants in BRCA1 and BRCA2 (12.5%) was lower in comparison with other studies. TP53 was the most altered gene in tumors, with 62.5% presenting likely non-functional or non-functional somatic variants, while eight 14.2% presented likely non-functional or non-functional somatic variants in BRCA1 or BRCA2.

Dataset Information

A population-based analysis of germline BRCA1 and BRCA2 testing among ovarian cancer patients in an era of histotype-specific approaches to ovarian cancer prevention.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets