Psychosocial factors predicting BRCA1/BRCA2 testing decisions in members of hereditary breast and ovarian cancer families.

Although BRCA1/2 testing has increasingly entered clinical practice, much is to be learned about the most effective ways to provide counseling to persons potentially interested in receiving test results. The purpose of this study was to identify factors affecting genetic testing decisions in a cohort of hereditary breast and ovarian cancer (HBOC) families presented with the choice to undergo testing. Relatives in these families are known to carry BRCA1 or BRCA2 mutations. Sociodemographics, personality traits, and family functioning were self-assessed using validated psychometric instruments at baseline. Among 172 individuals who participated in pretest education and counseling, 135 (78%) chose to undergo genetic testing and 37 (22%) chose not to be tested. Individuals who chose to undergo genetic testing were more likely to be older (> or =40 years), to have lower levels of optimism, and to report higher levels of cohesiveness in their families. A better understanding of factors that influence interest in predictive testing may help to inform the counseling that occurs prior to genetic testing.

Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including 1 family with male breast cancer.

Genetic epidemiological evidence suggests that mutations in BRCA1 may be responsible for approximately one half of early onset familial breast cancer and the majority of familial breast/ovarian cancer. The recent cloning of BRCA1 allows for the direct detection of mutations, but the feasibility of presymptomatic screening for cancer susceptibility is unknown. We analyzed genomic DNA from one affected individual from each of 24 families with at least three cases of ovarian or breast cancer, using SSCP assays. Variant SSCP bands were subcloned and sequenced. Allele-specific oligonucleotide hybridization was used to verify sequence changes and to screen DNA from control individuals. Six frameshift and two missense mutations were detected in 10 different families. A frameshift mutation was detected in a male proband affected with both breast and prostate cancer. A 40-bp deletion was detected in a patient who developed intra-abdominal carcinomatosis 1 year after prophylactic oophorectomy. Mutations were detected throughout the gene, and only one was detected in more than a single family. These results provide further evidence that inherited breast and ovarian cancer can occur as a consequence of a wide array of BRCA1 mutations. These results suggests that development of a screening test for BRCA1 mutations will be technically challenging. The finding of a mutation in a family with male breast cancer, not previously thought to be related to BRCA1, also illustrates the potential difficulties of genetic counseling for individuals known to carry mutations.

Anticipated uptake and impact of genetic testing in hereditary breast and ovarian cancer families.

In anticipation of the identification of the BRCA1 gene, we studied the interest in and anticipated reaction to DNA testing for mutations in this gene in members of high-risk families. We surveyed 91 female and 49 male subjects using a structured interview by study nurses. All subjects were members of inherited breast-ovarian cancer families participating in a genetic linkage study at the National Cancer Institute. The main outcomes of the study were interest in genetic testing and anticipated impact of test results. Seventy nine % of subjects indicated that they would "definitely" want to be tested, and 16% would "probably" want to be tested for mutations in the BRCA1 gene. Subjects with a high self-perceived risk of having an altered BRCA1 gene were more likely to definitely want testing (P = 0.02), while estimated true genetic risk did not predict interest in the test. Females were significantly more likely to definitely want testing (P = 0.005) and had a significantly greater mean anticipated negative-impact score (2.3) compared to males (1.0) (P < 0.001). We found a high level of interest in genetic testing for BRCA1 among members of inherited breast-ovarian cancer families participating in a genetic linkage study. While utilization may fall below levels of interest reported in this and other preliminary surveys, given the potential for early detection and treatment of breast and ovarian cancer, interest in BRCA1 testing may translate into high rates of uptake. These results indicate that it will be critical to incorporate follow-up counseling and support into BRCA1 testing programs.