Pilot Testing of a Psycho-educational Telephone Intervention for Women Receiving Uninformative BRCA1/2 Genetic Test Results.

Evidence suggests that women who receive uninformative results for breast and ovarian cancer (BRCA1/2) gene mutations may experience as much distress as women whose results indicate the presence of a gene mutation. No intervention to reduce distress after receipt of uninformative results has yet been tested. The purpose of this study was to test the feasibility and preliminary effects of a psycho-educational telephone (PET) intervention to reduce distress in women who receive uninformative BRCA1/2 results. A single group with repeated measures was used to assess the impact of the intervention on 72 such women. After receiving the results, most of the women continued to feel uncertain about their carrier genetic status. However, their distress significantly decreased between receipt of uninformative results and 3 months post-intervention (p = 0.01). The preliminary findings suggest that a PET uncertainty intervention is clinically feasible and may reduce the distress of receiving uninformative results.

Les données permettent de croire que les femmes qui obtiennent des résultats non concluants à la suite de tests de dépistage d'une mutation des gènes liés aux cancers du sein et des ovaires (BRCA1 et BRCA2) sont susceptibles d'éprouver une détresse aussi importante que celles dont les résultats indiquent la présence d'une mutation génétique. Aucune intervention visant à atténuer le sentiment de détresse après réception de résultats non concluants n'a encore été mise à l'essai. L'objectif de la présente étude est d'évaluer la faisabilité et les effets préliminaires d'une intervention consistant en un appel psycho-éducatif destiné à réduire la détresse de femmes ayant reçu des résultats de dépistage génétique non concluants concernant les gènes BRCA1 et BRCA2. Un groupe unique sondé à plusieurs reprises a été étudié afin d'évaluer l'effet d'une telle intervention sur 72 femmes. Après la réception de leurs résultats, la plupart éprouvaient toujours de l'incertitude concernant leur statut de porteuse ou non d'une mutation génétique. Toutefois, une diminution considérable de leur détresse a été observée entre la réception des résultats non concluants et une période de trois mois après l'intervention par téléphone (p = 0,01). Les constatations préliminaires donnent à penser qu'une intervention psycho-éducative par téléphone à propos de l'incertitude est réalisable et permet de réduire la détresse des femmes dont les résultats sont non concluants.

The importance of functional testing in the genetic assessment of Muir-Torre syndrome, a clinical subphenotype of HNPCC.

A majority of families with hereditary nonpolyposis colorectal cancer (HNPCC) are attributable to germline mutations in three DNA mismatch repair (MMR) genes, MLH1, MSH2 and MSH6. However, the clinical phenotype appears to reflect a complex interplay between the predisposing mutation and putative constitutional and somatic modifiers. Certain MMR gene mutations predispose to combined occurrence of cutaneous sebaceous gland neoplasms and visceral malignancies, which is known as Muir-Torre syndrome (MTS) and regarded as a phenotypic variant of HNPCC. The sebaceous tumors associated with MTS appear in many patients before visceral malignancies providing important predictability of HNPCC-related integral cancers in mutation carriers. Since most sebaceous skin tumors are, however, sporadic, the contribution of non-truncating mutations found in skin cancer patients is difficult to interpret and genetic assessment of MTS requires a functional test. Here, we studied the repair efficiency of the two MSH2 missense mutations, L187P and C697F, found in HNPCC families including a few mutation carriers with sebaceous skin tumors. Both mutations were completely deficient in an MMR assay, which together with tumor findings suggested their predisposing role in both internal and skin malignancies in the families.

BRCA1/2 predictive testing: a study of uptake in two centres.

Differences in reported uptake of genetic testing for mutations in BRCA1 and BRCA2 can largely be accounted for by different methodologies and by studying research vs nonresearch families. In our joint study of 75 nonresearch families from two UK centres in which at least 3 years had elapsed since the initial proband had been informed of the availability of testing, only 45 and 34% of eligible individuals from Manchester and London, respectively, had come forward for counselling. Final uptake rates using a non-proactive approach were 53 and 29% for women and 11-12% for men, but the figure among those attending clinic was 73 and 62%, respectively. Unlike previous studies, we did not find that uptake had stabilised after a year with 25% of those being tested more than 2 years after the family was informed, and several delaying a considerable time between genetics appointments. We believe that the particularly low uptake even of counselling in men may need to be addressed by improving family communication or providing information sheets for family members to disseminate.