Prevalence of founder mutations in the BRCA1 and BRCA2 genes among unaffected women from the Bahamas.

Population-based testing for BRCA1/2 mutations detects a high proportion of carriers not identified by cancer family history-based testing. We sought to determine whether population-based testing is an effective approach to genetic testing in the Bahamas, where 23% of women with breast cancer carry one of seven founder mutations in the BRCA1 or BRCA2 gene. We determined the prevalence of founder BRCA mutations in 1847 Bahamian women without a personal history of breast or ovarian cancer, unselected for age or family history. We found that 2.8% (20/705) of unaffected women with a family history of breast/ovarian cancer and 0.09% (1/1089) of unaffected women without a family history carry a BRCA mutation. A total of 38% of unaffected women with a known mutation in the family were found to carry the familial mutation. We previously suggested that all Bahamian women with breast or ovarian cancer be offered genetic testing. These current data suggest that additionally all unaffected Bahamian women with a family history of breast/ovarian cancer should be offered genetic testing for the founder BRCA mutations.

Strategies for recruitment of relatives of BRCA mutation carriers to a genetic testing program in the Bahamas.

The prevalence of BRCA1 and BRCA2 mutations among unselected breast cancer patients in the Bahamas is 23%. It is beneficial to advise relatives of mutation carriers that they are candidates for genetic testing. Women who test positive are then eligible for preventive interventions, such as oophorectomy. It is not clear how often relatives of women with a mutation in the Bahamas wish to undergo genetic testing for the family mutation. Furthermore, it is not clear how best to communicate this sensitive information to relatives in order to maximize patient compliance. We offered genetic testing to 202 first-degree relatives of 58 mutation carriers. Of 159 women who were contacted by the proband or other family member, only 14 made an appointment for genetic testing (9%). In contrast, among 32 relatives who were contacted directly by the genetic counselor, 27 came for an appointment (84%). This study suggests that for recruitment of relatives in the Bahamas, direct contact by counselor is preferable to using the proband as an intermediary.

Demographics of breast cancer in a small cohort of women in the Caribbean

OBJECTIVES: To address the prevalence and spectrum of breast cancer (BRCA1 and BRCA2) mutations in the Caribbean population. DESIGN AND METHODS: Demographic and clinical pathologic data was collected from 347 women of Afro-Caribbean decent. The cohort included women with breast cancer from the following countries: the Cayman Islands, Jamaica, Barbados, Dominica, Trinidad & Tobago and Haiti. RESULTS: The mean age of onset in the cohort was 48.1 yrs. with a mean body mass index (BMI) of 27.7. 70% of breast cancer cases were estrogen receptor-positive (ER+) (n=241) and in Jamaica 27% (n=105) of breast cancer cases were human epidermal growth factor receptor 2 positive (Her2+). Total Abdominal Hysterectomy Bilateral Salpingo Oophorectomy (TAH-BSO) delayed invasive breast cancer from 48 to 53 years (p=0.005). Parity was a significant factor (p<0.0001), which delayed age of onset by 8 yrs. Additionally, pregnancy alone delayed age of onset (p<0.005) by 8 yrs. Only three women out of 347 were found to have a mutation. CONCLUSIONS: This population-based study provided an insight into pattern of risk factors – both genetic and environmental of breast cancer incidence and subtype across the Caribbean. In conclusion 1) genetic causes of breast cancer appeared rare outside of the Bahamas, 2) fertility factors appeared important in the development of breast cancer, 3) TAH-BSO was common as both a form of contraception and because of the high incidence of fibroids, it may be protective, 4) BMI may impact on breast cancer development and 5) screening mammography was rare and the vast majority was diagnostic in nature.

The spectrum of BRCA1 and BRCA2 mutations in breast cancer patients in the Bahamas.

We sought to identify the full range of founder mutations in BRCA1 and BRCA2 in the Bahamas and to estimate the proportion of all BRCA1 and BRCA2 mutations that are accounted for by founder mutations. We studied 214 Bahamian women with invasive breast cancer, unselected for age or family history. A founder mutation had previously been identified in 49 patients. We conducted full sequencing of the BRCA1 and BRCA2 genes and multiplex ligation-dependent probe amplification (MLPA) for 156 patients. A novel founder mutation in BRCA2 (exon 17 818delA) was seen in four different patients and five other unique mutations in BRCA1 and BRCA2, including a large deletion (exons 8-9) in BRCA1. In total, a mutation was seen in 58 of the 214 patients (27%); 92% of carriers carried one of the seven founder mutations. Approximately 27% of unselected cases of breast cancer in the Bahamian population are attributable to a mutation in BRCA1 or BRCA2, a prevalence which far exceeds that of any other country. The majority of women who carry a mutation in the Bahamas, carry one of the seven founder mutations, making it possible to offer genetic testing to all women at risk for breast cancer in the Bahamas.