Nancy Feldman

Prevalence and Type of BRCA Mutations in Hispanics Undergoing Genetic Cancer Risk Assessment in the Southwestern United States: A Report From the Clinical Cancer Genetics Community Research Network

PURPOSE To determine the prevalence and type of BRCA1 and BRCA2 (BRCA) mutations among Hispanics in the Southwestern United States and their potential impact on genetic cancer risk assessment (GCRA). PATIENTS AND METHODS Hispanics (n = 746) with a personal or family history of breast and/or ovarian cancer were enrolled in an institutional review board-approved registry and received GCRA and BRCA testing within a consortium of 14 clinics. Population-based Hispanic breast cancer cases (n = 492) enrolled in the Northern California Breast Cancer Family Registry, negative by sequencing for BRCA mutations, were analyzed for the presence of the BRCA1 ex9-12del large rearrangement. RESULTS Deleterious BRCA mutations were detected in 189 (25%) of 746 familial clinic patients (124 BRCA1, 65 BRCA2); 21 (11%) of 189 were large rearrangement mutations, of which 62% (13 of 21) were BRCA1 ex9-12del. Nine recurrent mutations accounted for 53% of the total. Among these, BRCA1 ex9-12del seems to be a Mexican founder mutation and represents 10% to 12% of all BRCA1 mutations in clinic- and population-based cohorts in the United States. CONCLUSION BRCA mutations were prevalent in the largest study of Hispanic breast and/or ovarian cancer families in the United States to date, and a significant proportion were large rearrangement mutations. The high frequency of large rearrangement mutations warrants screening in every case. We document the first Mexican founder mutation (BRCA1 ex9-12del), which, along with other recurrent mutations, suggests the potential for a cost-effective panel approach to ancestry-informed GCRA.

Factor VII deficiency in pregnancy treated with recombinant factor VIIa.

BACKGROUND Factor VII deficiency is an autosomal recessive bleeding disorder with an incidence of one in 500,000. Few cases have been reported in pregnancy, and only two patients were treated with recombinant factor VIIa. In the past, fresh frozen plasma or factor VII concentrate has been the conventional treatment for this disorder. CASE We report a case of factor VII deficiency diagnosed during pregnancy with a factor VII level of 1%. After prophylactic treatment with recombinant factor VIIa, the patient did not manifest any signs or symptoms of excessive bleeding during labor or postpartum. CONCLUSION Given the inherent risks of transmission of human immunodeficiency virus and hepatitis with blood products, recombinant factor VIIa treatment is an alternative that is safe and effective during labor, delivery, and the puerperium.

Social‐cognitive aspects of underserved Latinas preparing to undergo genetic cancer risk assessment for hereditary breast and ovarian cancer

Objectives: As Latinos are a growing ethnic group in the United States, it is important to understand the socio‐cultural factors that may be associated with cancer screening and prevention in this population. The socio‐cultural factors that may affect preparedness to undergo genetic cancer risk assessment (GCRA) deserve particular attention. The pre‐GCRA period can provide insight into variables that may influence how medically underserved Latinas, with limited health resources and access, understand hereditary cancer information and subsequently implement cancer risk management recommendations. This study explores social, cognitive and cultural variables in Latinas prior to undergoing GCRA.

Abstract A50: Differences in perceived personal control among Latina women undergoing genetic cancer risk assessment for hereditary breast and ovarian cancer

Introduction: Genetic cancer risk assessment (GCRA) is a growing subspecialty that identifies individuals at risk for hereditary predisposition to cancer. Despite recognition of GCRA as a standard-of-care service, there are significant disparities in access to GCRA among at-risk underserved Latina women. Therefore, little is known about the emotional and decisional experience of Latinas undergoing GCRA. Previous studies have looked at the concept of perceived personal control (PPC) as an outcome variable of GCRA, measuring an individual9s feelings of control related to the possibility of having a hereditary condition. This study examined PPC among patients participating in a randomized controlled study examining the effect of an adapted motivational interview (AMI) pre-GCRA telephone intervention to promote uptake of GCRA by underserved Latinas. Purpose: To evaluate the influence of the AMI intervention and GCRA on PPC at baseline, immediately pre- and post-GCRA among English and Spanish-speaking Latinas at risk for hereditary breast and ovarian cancer. Method: Eligible participants were adult women who self-identified as Latina, understood English and/or Spanish, and met NCCN criteria for BRCA1 and BRCA2 testing. Participants were randomized to a motivational interview intervention, time and attention control, or usual care. A validated 9-item instrument to assess three dimensions of perceived personal control (behavioral, decisional, and cognitive control) over a genetic problem and the counseling process was translated to Spanish and verbally administered in the patients9 preferred language at baseline (prior to randomization) and immediately pre and post-GCRA. A higher PPC score indicates an increased sense of PPC. The three dimensions of PPC encompass a total PPC score. Results: Of the 411 participants, 323 (78.6%) were affected by breast cancer and 88 (21.4%) were unaffected at time of enrollment. Two-hundred and eighty-two (68.6%) were Spanish-speakers and 129 (31.4%) spoke English. While not significant, total PPC scores increased from baseline to post-GCRA and from pre-GCRA to post-GCRA, but decreased from baseline to pre-GCRA for all participants (the affected and unaffected individuals, including English and Spanish-speakers). Unaffected women had significantly higher total PPC scores than women affected with cancer (p=0.001). Unaffected patients had higher cognitive PPC scores at baseline (p=0.008), pre-GCRA (p=0.019), and post-GCRA (p=0.001) compared to the affected participants at all three time points. Unaffected individuals scored higher in behavioral PPC at post-GCRA than the affected participants (p=0.012). The unaffected individuals scored higher in decisional PPC at post-GCRA compared to the affected individuals (p=0.005). There were no significant differences in PPC scores between English and Spanish-speaking participants or between study arms. Conclusion: Cognitive, decisional, behavioral, and total PPC scores were highest at post-GCRA among all groups (unaffected and affected individuals, and English and Spanish-speakers). Unaffected individuals had higher cognitive PPC scores at all three times points compared to affected participants. Interestingly, the affected participants scored higher in behavioral PPC at baseline, but scored lower post-GCRA compared to those who are unaffected. This suggests that after receiving information during GCRA, the unaffected individuals may believe that they have more control over their health and opportunities for cancer prevention. Decrease in total PPC from baseline to pre-GCRA may be associated with pre-counseling anxiety. More investigation into the three dimensions of PPC should be conducted in order to better understand their distinctions and relationship to GCRA. Citation Format: Tanya A. Chavez, Bita Nehoray, Charite Ricker, Kathleen R. Blazer, Sharon Sand, Kimlin T. Ashing, Jaime Cordova, Gwen Uman, Kai Yang, Nancy Feldman, Jeffrey N. Weitzel. Differences in perceived personal control among Latina women undergoing genetic cancer risk assessment for hereditary breast and ovarian cancer. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A50.