Prophylactic Surgery Reduces Gynecologic Cancer Risk in Women w. Lynch Syndrome

Prophylactic Surgery Reduces Gynecologic Cancer Risk in Women with Lynch Syndrome

Preventive surgery to remove the uterus and ovaries appears to greatly reduce the risk of developing endometrial or ovarian cancer among women with Lynch Syndrome. These results were published in the New England
Journal of Medicine.

Lynch Syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), results from inherited mutations in genes involved in DNA mismatch repair.[1] These mutations greatly increase the risk of developing colorectal cancer and also increase the risk of several other cancers.

Average age at diagnosis of colorectal cancer is 44 years in individuals with an HNPCC mutation, compared to 64 years in the general population. Other cancers that are more common in HNPCC families include cancers of the endometrium (the lining of the uterus), ovary, small intestine, ureter, and renal pelvis.

Overall, roughly 3% to 5% of all colorectal cancers are thought to result from HNPCC mutations. The following families are more likely to have an HNPCC mutation: those with a family member diagnosed with an HNPCC-related cancer before the age of 50; HNPCC-related cancer in at least two generations, with at least three affected relatives; and no evidence of familial adenomatous polyposis (another inherited genetic condition linked with colorectal cancer). Consulting a physician or genetic counselor can help clarify the likelihood that a family carries an HNPCC mutation.

Because women with HNPCC mutations are at increased risk of developing endometrial and ovarian cancers, there is interest in the extent to which cancer risk can be decreased by prophylactic (preventive) surgery. Specifically, female mutation carriers may benefit from the surgical removal of their uterus (hysterectomy) and/or fallopian tubes and ovaries (salpingo-oophorectomy) before endometrial or ovarian cancer are diagnosed.

To assess the effect of prophylactic hysterectomy and oophorectomy among women with HNPCC mutations, researchers assessed cancer risk in 315 women-47 had undergone both hysterectomy and salpingo-oophorectomy, 14 had undergone hysterectomy alone, and 254 had not had prophylactic surgery.[2]

  • Endometrial cancer developed in 33% of women without prophylactic hysterectomy and none of the women with prophylactic hysterectomy.
  • Ovarian cancer developed in 5.5% of the women without prophylactic salpingo-oophorectomy and none of the women with prophylactic salpingo-oophorectomy.
  • Given the median ages at which endometrial and ovarian cancers developed in the women without prophylactic surgery (46 years for endometrial cancer and 42 years for ovarian cancer), the researchers note that it may be appropriate to consider prophylactic surgery after the age of 35, or once childbearing has been completed.

The researchers conclude that “prophylactic hysterectomy with bilateral salpingo-oophorectomy is an effective strategy for preventing endometrial and ovarian cancer in women with Lynch Syndrome.”

An accompanying editorial notes that many of the cancers that developed among women without prophylactic surgery were detected at stage I or stage II.[3] The editorial notes, “If gynecologic cancers associated with HNPCC are predominantly at an early stage and curable at the time of detection, the costs of prophylactic surgery (including premature menopause and its sequelae) may outweigh the benefits.”

In response to this and other arguments, the author of the editorial recommends that women with HNPCC mutations be offered either prophylactic surgery or frequent and intensive cancer screening beginning at a young age. Results from developing studies should provide additional evidence about the optimal approach to reducing the risk of gynecologic cancers in women with HNPCC mutations.

References:

[1] National Cancer Institute. Genetics of Colorectal Cancer (PDQ®). Health Professional Version. http://www.cancer.gov/cancertopics/pdq/genetics/colorectal (Accessed January 19, 2006).

[2] Schmeler KM, Lynch HT, Chen L-M et al. Prophylactic Surgery to Reduce the Risk of Gynecologic Cancers in the Lynch Syndrome. New England
Journal of Medicine. 2006;354:261-9.

[3] Offit K, Kauff ND. “Reducing the Risk of Gynecologic Cancer in the Lynch Syndrome.” New England
Journal of Medicine. 2006;354:293-295.

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