Managing healthcare for female BRCA carriers in the population screening era: developing a harmonized national policy for surveillance and risk-reduction

Background: The implementation of Israeli National screening for BRCA1/BRCA2 pathogenic variants (PVs) in 2020 has led to a significant increase in the number of unaffected female carriers who are referred to high-risk surveillance clinics (HRSCs). Lack of standardization in protocols for risk reduction and surveillance between HRSCs results in confusion and gaps in care. We aimed to identify discrepancies in existing practices and lead to policy development of a national policy for surveillance, management and risk reducing strategies in BRCA-PV carriers. Methods: A comparative analysis of risk reduction and surveillance protocols of the nine leading HRSCs across Israel, comprising the Israeli Consortium for hereditary breast and ovarian cancer (HBOC), and multi-center meetings to develop consensus guidelines for HRSCs. Results: Our analysis revealed a high level of prior consensus on critical aspects including risk-reducing mastectomy, salpingo-oophorectomy, fertility treatment, contraception, hormone replacement therapy, and general health behavior. For breast cancer (BC) imaging surveillance there was variability regarding frequency (e.g. only one HRSC offers biannual MRI for BRCA1 carriers), age limits (five centers continue in women older than 75 years), frequency during pregnancy and lactation (four HRSCs every three months and four others every six months; one does not recommend any surveillance), and surveillance post-mastectomy. For ovarian cancer (OvCa) surveillance, there was also variability: six centers recommend biannual/annual serum CA-125 level and pelvic sonography for all women, one center recommends this for all women till risk-reducing-bilateral-salpingo-oophorectomy (RRBSO), and two centers exclusively for women from age 35 till RRBSO. Surveillance recommendations for malignancies other than BC and OvCa differed greatly among centers.