Performance characteristics of brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed ovarian cancers.

Abstract

e22525 Background: Ovarian cancer (OC) is the third most common Lynch syndrome (LS)-associated cancer in women but there is no established screening strategy to identify LS in this population. An adequate family history may identify patients suspected of LS, prompting a referral to genetic assessment. We have previously validated the 4-item brief Family History Questionnaire (bFHQ) in endometrial cancers. The objective of this study was to assess whether bFHQ can be used as a screening tool to identify women with OC at risk of LS. Methods: Prospective cohort study recruited women with newly diagnosed non-serous/non-mucinous OC from three cancer centers in Ontario, Canada. Participants completed bHFQ, extended Family History Questionnaire (eFHQ; encompassing Amsterdam II criteria, Society of Gynecologic Oncology 20-25% criteria and Ontario Ministry of Health criteria), immunohistochemistry (IHC) for mismatch repair (MMR) proteins and universal germline testing for LS. The performance characteristics were compared between bFHQ, eFHQ, and IHC. Results: Of 215 participants, 169 (79%) were evaluable with both bFHQ and germline mutation status; 12 of these 169 were confirmed to have LS (7%). Nine of 12 patients (75%) with LS were correctly identified by bFHQ, compared to 6 of 11 (55%) by eFHQ and 11 of 13 (85%) by IHC. The sensitivity, specificity, positive predictive values and negative predictive values of bFHQ were 75%, 66%, 15% and 98%, compared to 55%, 92%, 35% and 96% for eFHQ and 85%, 90%, 39% and 99% for IHC respectively. IHC was the most sensitive and specific approach. The 4-item bFHQ was more sensitive than eFHQ and took less than 10 minutes for each patient to complete. Conclusions: Patient-administered bFHQ may serve as an adequate screening tool to triage women with OC for further genetic assessment for LS, especially in centers without access to universal tumor testing for IHC for MMR.[Table: see text]