Genetic testing for BRCA1 and BRCA2 in the Province of Ontario

Abstract

In 2001, genetic testing for BRCA1 and BRCA2 was introduced in Ontario, for women at high-risk of breast or ovarian cancer. To date over 30,000 individuals have been tested throughout Ontario. Testing was offered to all Ontario residents who were eligible under any of 13 criteria. We report the results of tests conducted at Mount Sinai Hospital from 2007 to 2014. A total of 4726 individuals were tested, 764 (16.2%) were found to carry a pathogenic variant (mutation). Among 3684 women and men who underwent testing without a known familial BRCA mutation, 331 (9.0%) were found to carry a mutation. Among 1042 women and men tested for a known family mutation, 433 (41.6%) were positive. There were 603 female mutation carriers, of these, 303 were affected with breast or ovarian cancer (50%) and 16 with another cancer (2.3%). Of 284 unaffected female carriers, 242 (85%) were tested for a known family mutation and 42 (15%) were the first person in the family to be tested. By placing greater emphasis on recruiting unaffected female relatives of known mutation carriers for testing, greater than one-half of newly identified carriers will be unaffected.

Efficacy versus effectiveness of clinical genetic testing criteria for BRCA1 and BRCA2 hereditary mutations in incident breast cancer

“…There has long been debate how to refine testing criteria, in order to improve sensitivity and specificity. We agree with Finch et al [6] that a 10% a priori probability of carrying a mutation to merit testing should now be considered outdated. Less strict criteria would allow for more mutation carriers to be identified.…”

“…Many studies have investigated efficacy of various BRCA testing criteria [6–9]. However, the results of these efficacy studies cannot be generalized to real world circumstances, because a mutation carrier can evade detection for other reasons than not fulfilling the selection criteria: i.e.…”

The Impact of Angelina Jolie (AJ)'s Story on Genetic Referral and Testing at an Academic Cancer Centre in Canada

“…In the province of Ontario, the Ministry of Health and Long Term Care (MOHLTC) has published guidelines outlining who should be offered genetic counseling based on their personal and/or family history of cancer and who qualifies for genetic testing (Genetic counseling eligibility, UHN). Genetic testing for BRCA1/2 was introduced in Ontario in 2001, and to date over 30,000 individuals have been tested (Finch et al 2015). Details of the guidelines are presented in Table 1.…”

Eligibility Criteria and Genetic Testing Results from a High-Risk Cohort for Hereditary Breast and Ovarian Cancer Syndrome in Southeastern Ontario

“…This could indicate that first-degree relatives of individuals with ovarian cancer have a 10% probability of carrying a mutation and might warrant expansion of criterion 4 to include first-degree relatives of those affected with ovarian cancer. 15 We demonstrate the importance of the VUS category, because the addition of VUS to our analyses improved the performance of some risk criteria to a better than 10% chance of identifying carriers. Clearly, understanding the pathogenicity of VUS will be critically important to dissect the true detection rate for any risk criterion.…”