Mother and Daughter Perspectives on Genetic Counseling and Testing of Adolescents for Hereditary Breast Cancer Risk.

OBJECTIVE: To evaluate the risks, benefits, and utility of testing for adult-onset hereditary breast and ovarian cancer (HBOC) in adolescents and young adults. STUDY DESIGN: We evaluated interest in genetic testing of adolescents for adult-onset HBOC genes through semistructured interviews with mothers and adolescents who had previously participated in breast cancer research or had pursued (mothers) clinical testing for HBOC. RESULTS: The majority of mothers (73%) and daughters (75%) were interested in the daughter having genetic testing and were motivated by the future medical utility and current social utility of relieving anxiety and allowing them to prepare. Mothers and daughters both reported that approximately 3 years in the future was the best time to test the daughter regardless of the current age of the daughter. Overall, both mothers and daughters expressed the importance of the involvement of the mother to provide educational and emotional support but ultimately it was the daughter's decision to test. Balancing the independence and maturity of the daughter while reinforcing communication and support within the dyad was a prominent theme throughout the interviews. CONCLUSIONS: There is interest among some high-risk adolescents and young adults to engage in genetic counseling and undergo testing. Providing pretest and posttest genetic counseling, assessing preferences for parent involvement, and offering psychosocial support may be important if genetic testing for HBOC is offered to adolescents and young adults before age 25 years.

The BRCA Self-Concept Scale: a new instrument to measure self-concept in BRCA1/2 mutation carriers.

UNLABELLED: Genetic testing for BRCA1/2 has psychosocial impacts including those related to views of personal health, sense of self and identity and body image. The centrality of a person's self-concept in maintaining physical and psychosocial well-being has been well recognized; however, to date research exploring altered self-concept related to carrier knowledge is limited. OBJECTIVE: The objective of the study was to develop and validate a scale to measure the self-concept among individuals testing positive for BRCA1/2 mutations. METHODS: The study was conducted in two phases: phase I: item generation and refinement and phase II: scale selection and initial validation. During phase I, scale items were generated through individual interviews and focus groups of women with BRCA1/2 mutations, including women with or without a prior diagnosis of cancer. In phase II items were selected based on several criteria resulting in a 25-item scale, which underwent a reliability analyses and preliminary validation with 115 women. A second sample of 126 women was used to conduct further validation and samples were pooled to conduct factor analysis and the final scale selection. RESULTS: A 17-item self-concept scale emerged having three factors: stigma, vulnerability and mastery demonstrating evidence for an instrument with promising psychometric properties (total scale alpha=0.90). CONCLUSIONS: The scale has direct relevance for research in facilitating our understanding of the specific aspects of the self, which are vulnerable to BRCA1/2 testing and which play a role in clinical outcomes, to facilitate the development and specific testing of interventions and may be used as an outcome measure. Specific measurement tools for genetic populations will ultimately assist in the clinical management of these populations.

AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study.

The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.

BRCA1 and BRCA2 mutations in Turkish familial and non-familial ovarian cancer patients: a high incidence of mutations in non-familial cases.

Ovarian cancer is a clinically important cancer in Turkey. The contribution of BRCA1 and BRCA2 to ovarian cancer in Turkish patients has not previously been described. In this study we investigated the presence of BRCA1 and BRCA2 mutations in 102 consecutively ascertained, hospital-based, ovarian cancer cases. Four out of 15 (26.7%, 95% confidence interval (CI), 7.8%-55.1%) familial cases were found to carry mutations in BRCA1. Thirteen of the 87 (14.9%, 95% CI, 7.5%-22.4%) non-familial cases had BRCA1 and BRCA2 mutations, six in BRCA1, and seven in BRCA2. We have further studied the non-familial ovarian cancer cases to determine which subgroups have a likelihood of carrying clinically important mutations. Our study shows that those Turkish ovarian cancer patients with serous histopathology harbor a high proportion of mutations (12/58, 20.7%, 95% CI, 10.3%-31.1%) compared to all non-familial cases (14.9%) regardless of pathology. Within the serous sub-group, those that were also diagnosed below age 50 have an even greater percentage of mutations (8/28, 28.6%, 95% CI, 11.8%-45.3%). Our findings demonstrate that a substantial proportion of Turkish ovarian cancer patients, both with and without a family history, carry BRCA1 and BRCA2 mutations, demonstrating the importance of BRCA1 and BRCA2 in the development of ovarian cancer in this population.

Characteristics associated with participation at various stages at the Ontario site of the cooperative family registry for breast cancer studies.

PURPOSE: The Ontario site of the Cooperative Family Registry for Breast Cancer Studies collects cancer family history, other risk factor information, and biospecimens from individuals with incident breast cancer and their relatives within a defined population. Sampling is based on age and defined genetic risk criteria. The purpose of this analysis was to evaluate the representativeness of the respondents. METHODS: We examined characteristics associated with response to requests for information, biospecimens, and permission to contact relatives among those diagnosed with breast cancer in 1996 in the province of Ontario. RESULTS: Overall, response was good among the largest group, white women, and did not differ between those with and without a family history of breast and/or ovarian cancer. Women who described themselves as other than white and men tended to have lower response. Women of Ashkenazi heritage had high response except for permission to contact relatives. CONCLUSIONS: There was no evidence that participation in a familial breast cancer registry derived from a population-based cancer registry was influenced by having a family history of breast or ovarian cancer. The use of a cancer registry approach is likely more representative of the population than clinic-based recruitment of families for genetic studies.