Impact of genetic testing on endometrial cancer risk-reducing practices in women at risk for Lynch syndrome

Abstract

OBJECTIVE Due to the increased lifetime risk of endometrial cancer (EC), guidelines recommend that women with Lynch syndrome (LS) age ≥35 undergo annual EC surveillance or prophylactic hysterectomy (PH). The aim of this study was to examine the uptake of these risk-reducing strategies. METHODS The study population included women meeting clinical criteria for genetic evaluation for LS. Data on cancer risk-reducing behaviors were collected from subjects enrolled in two distinct studies: (1) a multicenter cross-sectional study involving completion of a one-time questionnaire, or (2) a single-center longitudinal study in which subjects completed questionnaires before and after undergoing genetic testing. The main outcome was uptake of EC risk-reducing practices. RESULTS In the cross-sectional cohort, 58/77 (75%) women at risk for LS-associated EC reported engaging in EC risk-reduction. Personal history of genetic testing was associated with uptake of EC surveillance or PH (OR 17.1; 95% CI 4.1–70.9). Prior to genetic testing for LS, 26/40 (65%) women in the longitudinal cohort reported engaging in EC risk-reduction. At one-year follow-up, 16/16 (100%) mismatch repair (MMR) gene mutation carriers were adherent to guidelines for EC risk-reduction, 9 (56%) of whom had undergone PH. By three-year follow-up, 11/16 (69%) MMR mutation carriers had undergone PH. Among women with negative or uninformative genetic test results, none underwent PH after testing. CONCLUSIONS Genetic testing for LS is strongly associated with uptake of EC risk-reducing practices. Women found to have LS in this study underwent prophylactic gynecologic surgery at rates comparable to those published for BRCA1/2 mutation carriers.

When is Genomic Testing Cost-Effective? Testing for Lynch Syndrome in Patients with Newly-Diagnosed Colorectal Cancer and Their Relatives

“…The authors concluded that excluding TAH/BSO would have little effect for female probands and mutation carriers, but would substantially reduce costs, thus leading to a lower ICER. Economic analyses specific to gynecologic cancers in LS have concluded that TAH/BSO is likely to be highly cost-effective [ 44 , 45 , 46 ].…”

How does genetic risk information for Lynch syndrome translate to risk management behaviours?

“…Screening recommendations are less clearly established for associated GC, with a suggestion that women should consider starting annual pelvic ultrasounds with endometrial sampling between 30 and 35 years of age for the detection of endometrial cancer, however the evidence of benefit is weak [10]. To date, no benefit has been shown for ovarian cancer screening [11]. The only effective intervention to reduce the risk of GC in women is prophylactic hysterectomy and bilateral salphingo-oophorectomy (BSO) from age 40 years, or once they have completed childbearing [12, 13].…”

Decisions about prophylactic gynecologic surgery: a qualitative study of the experience of female Lynch syndrome mutation carriers

“…A recent study reported that LS carriers were compliant with guidelines for cancer risk reduction in the year following genetic testing, with nearly 70% opting for prophylactic hysterectomy by three-year follow up [ 17 ]. Research suggests prophylactic surgery decisions are complex, driven by demographics (e.g., age, parity), medical factors (e.g., mutation status or abnormal ovarian screening results) and psychosocial factors (e.g., anxiety about cancer risk) [ 14 ]-[ 18 ].…”