Prophylactic Surgery to Reduce the Risk of Gynecologic Cancers in the Lynch Syndrome
Kathleen M. Schmeler, M.D., Henry T. Lynch, M.D., Lee-may Chen, M.D., Mark F. Munsell, M.S., Pamela T. Soliman, M.D., Mary Beth Clark, M.S.W., Molly S. Daniels, M.S., Kristin G. White, B.S., Stephanie G. Boyd-Rogers, R.N., Peggy G. Conrad, M.S., Kathleen Y. Yang, M.D., Mary M. Rubin, Ph.D., Charlotte C. Sun, Dr.P.H., Brian M. Slomovitz, M.D., David M. Gershenson, M.D., and Karen H. Lu, M.D.
Background Women with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have a 40 to 60 percent lifetime risk of endometrial cancer and a 10 to 12 percent lifetime risk of ovarian cancer.
The benefit of prophylactic gynecologic surgery for women with this syndrome has been uncertain. We designed this study to determine the reduction in the risk of gynecologic cancers associated with prophylactic hysterectomy and bilateral salpingo-oophorectomy in women with the Lynch syndrome.
Methods Three hundred fifteen women with documented germ-line mutations associated with the Lynch syndrome were identified.
Women who had undergone prophylactic hysterectomy (61 women) and women who had undergone prophylactic bilateral salpingo-oophorectomy (47 women) were matched with mutation-positive women who had not undergone the procedure in question (210 women for the analysis of endometrial cancer and 223 for the analysis of ovarian cancer).
Women who had undergone prophylactic surgery and their matched controls were followed from the date of the surgery until the occurrence of cancer or until the data were censored at the time of the last follow-up visit.
Results There were no occurrences of endometrial, ovarian, or primary peritoneal cancer among the women who had undergone prophylactic surgery. Endometrial cancer was diagnosed in 69 women in the control group (33 percent), for an incidence density of 0.045 per woman-year, yielding a prevented fraction (the proportion of potential new cancers prevented) of 100 percent (95 percent confidence interval, 90 to 100 percent).
Ovarian cancer was diagnosed in 12 women in the control group (5 percent), for an incidence density of 0.005 per woman-year, yielding a prevented fraction of 100 percent (95 percent confidence interval, –62 to 100 percent).
Conclusions These findings suggest that prophylactic hysterectomy with bilateral salpingo-oophorectomy is an effective strategy for preventing endometrial and ovarian cancer in women with the Lynch syndrome.
From the Departments of Gynecologic Oncology (K.M.S., P.T.S., K.G.W., S.G.B.-R., C.C.S., B.M.S., D.M.G., K.H.L.), Biostatistics and Applied Mathematics (M.F.M.), and Clinical Cancer Genetics (M.S.D.), the University of Texas M.D. Anderson Cancer Center, Houston; the Department of Preventive Medicine, Creighton University, Omaha, Nebr. (H.T.L., M.B.C.); and the Departments of Gynecologic Oncology (L.C., K.Y.Y., M.M.R.) and Medicine (P.G.C.), University of California at San Francisco, San Francisco.
Address reprint requests to Dr. Lu at the Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, P.O. Box 301439, Unit 1362, Houston, TX 77230-1439, or at firstname.lastname@example.org.
NEJM,Volume 354:261-269 January 19, 2006 Number 3
ASCO Press Release, 2006
J Clinical Oncology, March, 2008
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