Recommendation 5

• RRSO should be offered to women who harbour a pathogenic or likely pathogenic variant in BRCA1 after the age of 35 and BRCA2 from between 40 and 45 years for ovarian/tubal/peritoneal carcinoma risk reduction.

• For women diagnosed as pathogenic variant carriers after menopause, RRSO should be offered upon diagnosis.

• RRSO should be considered for breast cancer risk reduction in women younger than 50 years who harbour a pathogenic or likely pathogenic variant in BRCA2.

• After a breast cancer diagnosis, RRSO for breast cancer mortality reduction can be considered within two years to women who harbour a pathogenic or likely pathogenic variant in BRCA1 if younger than the recommended age range for ovarian cancer risk reduction. RRSO before the age of 40 and specifically for breast cancer treatment in BRCA2 should be considered only if recommended by their breast cancer oncologist. This is endorsed from Jacobson et al. 2018 [23].

Qualifying Statements for Recommendation 5

• In a Canadian cohort study, 3722 unaffected women who harboured a pathogenic or likely pathogenic variant in BRCA1 and BRCA2 who had undergone only RRSO were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. In BRCA1 carriers, HRs of breast cancer after RRSO were not significant at 0.96 (95% CI, 0.73 to 1.26), nor were they significant in BRCA2 carriers (HR, 0.65; 95% CI, 0.37 to 1.16). However, when the latter group was stratified by age, RRSO had a significant reduction in breast cancer incidence when it was performed before the age of 50 years (HR, 0.18; 95% CI, 0.05 to 0.63) [30].

Key Evidence for Recommendation 5

We endorse the recommendations from the clinical practice guideline conducted by Jacobson et al. [23] on behalf of the SOGC. This guideline scored well on the AGREE II scale. The scores are reported in Table 4–3 in Section 4 of this document. The evidence underpinning the recommendations is primarily comprised of a guideline from 2017 and comparative studies.

Justification for Recommendation 5

The Working Group members are confident in their endorsement of this recommendation. The source had adequate quality ratings, there is an excellent alignment with research questions of interest to the Working Group, methods and evidence and synthesis are convincing, and the treatments and patients included in the evidence base are generalizable to the Ontario context.