Rates of risk-reducing salpingo-oophorectomy in patients with CHEK2 mutations in a large healthcare system

Abstract

Objectives: CHEK2 mutations are associated with increased risk of breast, colon, and prostate cancer but not ovarian cancer. Our study investigated if women with CHEK2 mutations underwent risk reducing salpingo-oophorectomies (RRSO), despite no known risk of ovarian cancer associated with CHEK2, and if personal or family history of ovarian cancer was related to uptake of salpingo-oophorectomy. Methods: Retrospective cohort study was conducted from 2015-2018 in a large integrated healthcare system. Eligible patients were female, at least 18 years old and identified as CHEK2 mutation carriers. Those with concurrent non-CHEK2 pathogenic gene mutations were excluded. Surgical indications, personal history, family history up to third degree relatives, and mutation type were collected retrospectively. Primary outcome was RRSO rates among women with pathogenic CHEK2 mutation. Secondary outcomes included association of personal and family cancer history in patients with salpingo-oophorectomy. Results: Of 11,640 men and women who had genetic testing, 150 (1.3%) were identified with pathogenic CHEK2 mutation. 37 patients were excluded because they had more than one gene mutation, and 11 men in the remaining cohort were excluded, resulting in 102 women with a pathogenic CHEK2 mutation in the final cohort. A total of eighteen (18%) patients underwent uni- or bilateral salpingo-oophorectomy (BSO) for any reason, and six (6%) were for risk-reduction. Mean age at time of surgery was 53.0 years for all patients who underwent salpingo-oophorectomy and 54.4 years for those who underwent RRSO. Four (4%) patients total had personal history of ovarian cancer. 24 (24%) patients had family history of ovarian cancer. Four (67%) of the six patients who underwent RRSO had family history of ovarian cancer (p=0.03). Of the two patients without family history: one chose to have BSO for risk-reducing purposes as opposed to follow up for a unilateral benign ovarian cyst after being counseled that there was no increased risk of ovarian cancer and the other chose BSO for hormonal management of breast cancer but also cited risk reduction of ovarian cancer as an indication. Conclusions: Although, personal history of ovarian cancer is uncommon, family history of ovarian cancer is present in almost one quarter of CHEK2 mutation carriers. Most women with CHEK2 mutations did not have RRSO and the majority of those who chose RRSO had family history of ovarian cancer. This suggests that women and providers correctly assessed risk of ovarian cancer related to CHEK2, with few electing for RRSO because of increased perceived risk.