Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report

Dominguez-Valentin, M.; Crosbie, E.J.; Engel, C.; Aretz, S.; Macrae, F.; Winship, I.; ... ; Moller, P. (2020)

Article / Letter to editor

Purpose To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants. Methods The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. Results Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. Conclusion Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.

• All authors: Dominguez-Valentin, M.; Crosbie, E.J.; Engel, C.; Aretz, S.; Macrae, F.; Winship, I.; Capella, G.; Thomas, H.; Nakken, S.; Hovig, E.; Nielsen, M.; Sijmons, R.H.; Bertario, L.; Bonanni, B.; Tibiletti, M.G.; Cavestro, G.M.; Mints, M.; Gluck, N.; Katz, L.; Heinimann, K.; Vaccaro, C.A.; Green, K.; Lalloo, F.; Hill, J.; Schmiegel, W.; Vangala, D.; Perne, C.; Strauss, H.G.; Tecklenburg, J.; Holinski-Feder, E.; Steinke-Lange, V.; Mecklin, J.P.; Plazzer, J.P.; Pineda, M.; Navarro, M.; Vidal, J.B.; Kariv, R.; Rosner, G.; Pinero, T.A.; Gonzalez, M.L.; Kalfayan, P.; Ryan, N.; Broeke, S.W. ten; Jenkins, M.A.; Sunde, L.; Bernstein, I.; Burn, J.; Greenblatt, M.; Cappel, W.H.D.T.N.; Valle, A. della; Lopez-Koestner, F.; Alvarez, K.; Buttner, R.; Gorgens, H.; Morak, M.; Holzapfel, S.; Huneburg, R.; Doeberitz, M.V.; Loeffler, M.; Rahner, N.; Weitz, J.; Pylvanainen, K.; Renkonen-Sinisalo, L.; Lepisto, A.; Auranen, A.; Hopper, J.L.; Win, A.K.; Haile, R.W.; Lindor, N.M.; Gallinger, S.; Marchand, L. le; Newcomb, P.A.; Figueiredo, J.C.; Thibodeau, S.N.; Therkildsen, C.; Okkels, H.; Ketabi, Z.; Denton, O.G.; Rodland, E.A.; Vasen, H.; Neffa, F.; Esperon, P.; Tjandra, D.; Moslein, G.; Sampson, J.R.; Evans, D.G.; Seppala, T.T.; Moller, P.
• Date: 2020-12-01
• Journal: Genetics in Medicine
• Volume: 23
• Issue: 4
• Pages: 705 - 712
• DOI: doi:10.1038/s41436-020-01029-1
• Link: https://www.sciencedirect.com/science/article/pii/S1098360021024485?via%...