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. 2012 Dec;127(3):544-51.
doi: 10.1016/j.ygyno.2012.08.031. Epub 2012 Aug 29.

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

Matthew B Yurgelun  1 , Rowena Mercado, Margery Rosenblatt, Monica Dandapani, Wendy Kohlmann, Peggy Conrad, Amie Blanco, Kristen M Shannon, Daniel C Chung, Jonathan Terdiman, Stephen B Gruber, Judy E Garber, Sapna Syngal, Elena M Stoffel
Affiliations

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

Matthew B Yurgelun et al. Gynecol Oncol. 2012 Dec.

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.

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Conflict of interest statement

Conflict of interest statements:

Dr. Gruber reports serving as a consultant for Myriad Genetics.

Dr. Syngal reports serving as an advisor and consultant for Quest Diagnostics, Inc. and for Archimedes, Inc.

All other authors report no conflicts of interest.

Figures

Figure 1
Figure 1
CONSORT diagram for Cohort 1 and Cohort 2.
Figure 2
Figure 2
Endometrial cancer (EC) risk-reducing practices in a longitudinal cohort of women before and after genetic testing for Lynch syndrome. (A) Overall percentage of subjects engaging in EC risk-reductiona at baseline and one yearb after genetic testing. (B) Cumulative rates of prophylactic hysterectomy (PH) at baseline and at one- and three-year follow-up. (C) Rates of annual EC surveillance at baseline and at one-year follow-up. a “Engaging in EC risk-reduction” defined as either (1) having had a PH, (2) reporting annual EC surveillance by transvaginal ultrasound and/or endometrial biopsy, and/or (3) age <35 years old. b Uptake in EC risk-reduction at one-year follow-up is not reported for subjects found to have “true negative” genetic test results, since they would no longer be considered at risk for Lynch-associated EC.
Figure 2
Figure 2
Endometrial cancer (EC) risk-reducing practices in a longitudinal cohort of women before and after genetic testing for Lynch syndrome. (A) Overall percentage of subjects engaging in EC risk-reductiona at baseline and one yearb after genetic testing. (B) Cumulative rates of prophylactic hysterectomy (PH) at baseline and at one- and three-year follow-up. (C) Rates of annual EC surveillance at baseline and at one-year follow-up. a “Engaging in EC risk-reduction” defined as either (1) having had a PH, (2) reporting annual EC surveillance by transvaginal ultrasound and/or endometrial biopsy, and/or (3) age <35 years old. b Uptake in EC risk-reduction at one-year follow-up is not reported for subjects found to have “true negative” genetic test results, since they would no longer be considered at risk for Lynch-associated EC.
Figure 2
Figure 2
Endometrial cancer (EC) risk-reducing practices in a longitudinal cohort of women before and after genetic testing for Lynch syndrome. (A) Overall percentage of subjects engaging in EC risk-reductiona at baseline and one yearb after genetic testing. (B) Cumulative rates of prophylactic hysterectomy (PH) at baseline and at one- and three-year follow-up. (C) Rates of annual EC surveillance at baseline and at one-year follow-up. a “Engaging in EC risk-reduction” defined as either (1) having had a PH, (2) reporting annual EC surveillance by transvaginal ultrasound and/or endometrial biopsy, and/or (3) age <35 years old. b Uptake in EC risk-reduction at one-year follow-up is not reported for subjects found to have “true negative” genetic test results, since they would no longer be considered at risk for Lynch-associated EC.
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