DNA-testing for <it>BRCA1/2</it> prior to genetic counselling in patients with breast cancer: design of an intervention study, DNA-direct

Abstract Background Current practice for patients with breast cancer referred for genetic counseling, includes face-to-face consultations with a genetic counselor prior to and following DNA-testing. This is based on guidelines regarding Huntington’s disease in anticipation of high psychosocial impact of DNA-testing for mutations in BRCA1/2 genes. The initial consultation covers generic information regarding hereditary breast cancer and the (im)possibilities of DNA-testing, prior to such testing. Patients with breast cancer may see this information as irrelevant or unnecessary because individual genetic advice depends on DNA-test results. Also, verbal information is not always remembered well by patients. A different format for this information prior to DNA-testing is possible: replacing initial face-to-face genetic counseling (DNA-intake procedure) by telephone, written and digital information sent to patients’ homes (DNA-direct procedure). Methods/design In this intervention study, 150 patients with breast cancer referred to the department of Clinical Genetics of the Radboud University Nijmegen Medical Centre are given the choice between two procedures, DNA-direct (intervention group) or DNA-intake (usual care, control group). During a triage telephone call, patients are excluded if they have problems with Dutch text, family communication, or of psychological or psychiatric nature. Primary outcome measures are satisfaction and psychological distress. Secondary outcome measures are determinants for the participant’s choice of procedure, waiting and processing times, and family characteristics. Data are collected by self-report questionnaires at baseline and following completion of genetic counseling. A minority of participants will receive an invitation for a 30 min semi-structured telephone interview, e.g. confirmed carriers of a BRCA1/2 mutation, and those who report problems with the procedure. Discussion This study compares current practice of an intake consultation (DNA-intake) to a home informational package of telephone, written and digital information (DNA-direct) prior to DNA-testing in patients with breast cancer. The aim is to determine whether DNA-direct is an acceptable procedure for BRCA1/2 testing, in order to provide customized care to patients with breast cancer, cutting down on the period of uncertainty during this diagnostic process. Trial registration The study is registered at the Dutch Trial Registry http://www.trialregister.nl (NTR3018).</p

Stopping ovarian cancer screening in BRCA1/2 mutation carriers: Effects on risk management decisions & outcome of risk-reducing salpingo-oophorectomy specimens

Objective: Ovarian cancer screening (OCS) for BRCA1/2 mutation carriers was stopped in our family cancer clinic in 2009 because of its ineffectiveness. The study objective was to investigate the effect of stopping OCS on the timing and uptake of risk-reducing salpingo-oophorectomy (RRSO) and on the percentage of occult cancers in the specimens. Methods: 419 BRCA1/2 mutation carriers were recruited between January 1999 and June 2013. Uptake, timing and the outcome of the RRSO specimens before stopping OCS (period I) were compared to those after stopping OCS (period II). Results: The percentage of women undergoing RRSO within the recommended age range increased from 81% to 95%. Receiving DNA test results in period II independently predicted a shorter time interval to RRSO (hazard ratio: 2.48,95% confidence interval: 1.81-3.39). The incidence of detecting occult cancers in RRSO specimens before and after stopping OCS was 1.3% and 1.8%, respectively, and was not statistically significantly different. Conclusions: The presentation of risk management options to women may influence their decision. The increased patient awareness of the ineffectiveness of OCS could have led to a higher percentage of women undergoing RRSO and doing so more often within the recommended age range. (C) 2014 Elsevier Ireland Ltd. All rights reserved

Novel BRCA1 and BRCA2 Tumor Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas

With the recent introduction of Poly(ADP‐ribose) polymerase inhibitors, a promising novel therapy has become available for ovarian carcinoma (OC) patients with inactivating BRCA1 or BRCA2 mutations in their tumor. To select patients who may benefit from these treatments, assessment of the mutation status of BRCA1 and BRCA2 in the tumor is required. For reliable evaluation of germline and somatic mutations in these genes in DNA derived from formalin‐fixed, paraffin‐embedded (FFPE) tissue, we have developed a single‐molecule molecular inversion probe (smMIP)‐based targeted next‐generation sequencing (NGS) approach. Our smMIP‐based NGS approach provides analysis of both strands of the open reading frame of BRCA1 and BRCA2, enabling the discrimination between real variants and formalin‐induced artefacts. The single molecule tag enables compilation of unique reads leading to a high analytical sensitivity and enabling assessment of the reliability of mutation‐negative results. Multiplex ligation‐dependent probe amplification (MLPA) and Methylation‐specific multiplex ligation‐dependent probe amplification (MS‐MLPA) were used to detect exon deletions of BRCA1 and methylation of the BRCA1 promoter, respectively. Here, we show that this combined approach allows the rapid and reliable detection of both germline and somatic aberrations affecting BRCA1 and BRCA2 in DNA derived from FFPE OCs, enabling improved hereditary cancer risk assessment and clinical treatment of ovarian cancer patients

DNA-testing for BRCA1/2 prior to genetic counselling in patients with breast cancer: design of an intervention study, DNA-direct

Contains fulltext : 110772.pdf (publisher's version ) (Open Access)BACKGROUND: Current practice for patients with breast cancer referred for genetic counseling, includes face-to-face consultations with a genetic counselor prior to and following DNA-testing. This is based on guidelines regarding Huntington's disease in anticipation of high psychosocial impact of DNA-testing for mutations in BRCA1/2 genes. The initial consultation covers generic information regarding hereditary breast cancer and the (im)possibilities of DNA-testing, prior to such testing. Patients with breast cancer may see this information as irrelevant or unnecessary because individual genetic advice depends on DNA-test results. Also, verbal information is not always remembered well by patients. A different format for this information prior to DNA-testing is possible: replacing initial face-to-face genetic counseling (DNA-intake procedure) by telephone, written and digital information sent to patients' homes (DNA-direct procedure). METHODS/DESIGN: In this intervention study, 150 patients with breast cancer referred to the department of Clinical Genetics of the Radboud University Nijmegen Medical Centre are given the choice between two procedures, DNA-direct (intervention group) or DNA-intake (usual care, control group). During a triage telephone call, patients are excluded if they have problems with Dutch text, family communication, or of psychological or psychiatric nature. Primary outcome measures are satisfaction and psychological distress. Secondary outcome measures are determinants for the participant's choice of procedure, waiting and processing times, and family characteristics. Data are collected by self-report questionnaires at baseline and following completion of genetic counseling. A minority of participants will receive an invitation for a 30 min semi-structured telephone interview, e.g. confirmed carriers of a BRCA1/2 mutation, and those who report problems with the procedure. DISCUSSION: This study compares current practice of an intake consultation (DNA-intake) to a home informational package of telephone, written and digital information (DNA-direct) prior to DNA-testing in patients with breast cancer. The aim is to determine whether DNA-direct is an acceptable procedure for BRCA1/2 testing, in order to provide customized care to patients with breast cancer, cutting down on the period of uncertainty during this diagnostic process