The demand for BRCA1 and BRCA2 mutation screening is increasing as their identification will affect medical management. However, both the contribution of different mutation types in BRCA1 and BRCA2 and whom should be offered testing for large genomic rearrangements have not been well established in the U.S. high-risk population. We define the prevalence and spectrum of point mutations and genomic rearrangements in BRCA genes in a large U.S. highrisk clinic population of both non-Ashkenazi and Ashkenazi Jewish descent, using a sample set representative of the U.S. genetic testing population. Two hundred fifty-one probands ascertained through the University of Pennsylvania high-risk clinic, all with commercial testing for BRCA1 and BRCA2, with an estimated prevalence of BRCA mutation z10% using the Myriad II model and a DNA sample available, were studied. Individuals without deleterious point mutations were screened for genomic rearrangements in BRCA1 and BRCA2. In the 136 non-Ashkenazi Jewish probands, 36 (26%) BRCA point mutations and 8 (6%) genomic rearrangements (7 in BRCA1 and 1 in BRCA2) were identified. Forty-seven of the 115 (40%) Ashkenazi Jewish probands had point mutations; no genomic rearrangements were identified in the group without mutations. In the non-Ashkenazi Jewish probands, genomic rearrangements constituted 18% of all identified BRCA mutations; estimated mutation prevalence (Myriad II model) was not predictive of their presence. Whereas these findings should be confirmed in larger sample sets, our data suggest that genomic rearrangement testing be considered in all non-Ashkenazi Jewish women with an estimated mutation prevalence z10%.

Age greater than 40 years, parity, and a personal history of breast cancer were associated with choosing prophylactic BSO in our cohort. A short time interval was noted from the time of receiving positive genetic test results to undergoing prophylactic surgery.

BACKGROUND.Women who are at increased risk for breast and ovarian cancers, especially BRCA1 and BRCA2 mutation carriers, face a myriad of risk‐reduction options, including increased surveillance, chemoprevention, prophylactic oophorectomy, and prophylactic mastectomy. However, little is known about which clinical, demographic, or cancer‐related factors are associated with risk‐reduction interventions.METHODS.The authors conducted a retrospective review of records for 554 women who had undergone testing at The University of Texas M. D. Anderson Cancer Center between 2000 and 2006 for deleterious BRCA1 and BRCA2 gene mutations. Data were collected on the risk‐reduction interventions these women adopted after they underwent genetic testing. These data were tested for associations with demographic and clinical characteristics.RESULTS.Among the 554 women who underwent genetic testing for BRCA mutation, 78 were found to have a deleterious mutation in the BRCA1 gene, and 54 had a mutation in the BRCA 2 gene. Of the 554 women, 85 underwent prophylactic mastectomy, 30 prophylactic oophorectomy, and 52 both surgeries; 387 women opted for surveillance. Women who had BRCA mutations, a history of breast cancer or ductal carcinoma in situ (DCIS), or previous breast biopsies were more likely to have prophylactic surgery. Women with a family history of ovarian cancer were more likely to undergo prophylactic oophorectomy. Women with a personal history of ovarian cancer or advanced breast cancer were more likely to undergo surveillance only. Women with breast cancer who had had a total mastectomy as part of their prior breast cancer treatment underwent prophylactic mastectomy more frequently than women who either had breast‐conserving surgery or no history of breast cancer. In multivariate analysis, only positive BRCA mutation carrier status was associated with having had prophylactic surgery. In addition, breast cancer history was significantly associated with prophylactic mastectomy.CONCLUSIONS.Women who were BRCA carriers, women who had a history of breast cancer, DCIS, or breast biopsy, or had a family history of ovarian cancer were more likely to have undergone surgery for cancer risk reduction. Women with ovarian cancer or advanced breast cancer were more likely to have undergone surveillance. Cancer 2006. © 2006 American Cancer Society.

We report on benign multicystic peritoneal mesothelioma in two siblings whose family had a history of multiple familial diseases including diverticulosis. After a genetic evaluation and a chromosomal analysis, we were not able to identify a specific genetic cause of the family's pattern of disease. We assumed that previous surgical procedures and the chronic inflammatory process from diverticulitis were the underlying etiology. Both patients had multiple recurrences with indolent courses similar to those reported in other cases. After the recurrences, one patient was treated with cystic aspiration and the other with hormones. The cysts in both cases regressed partially but the patients were relieved of their clinical symptoms, for 2 years after cystic drainage in one case and for 5 years after hormonal treatment in the other.

Deleterious BRCA1 and BRCA2 mutations occur at considerable frequency within the Hispanic population, many of which have been identified previously in other ethnic populations. The BRCAPRO model appears to perform equally well in Hispanics as in whites.