ENDOMETRIAL CANCER

For women with problematic symptoms that are unresponsive to other drugs, short-term estrogen may be an option. Estrogen in this setting is unlikely to significantly increase the recurrence rate of endometrial cancer

This prospective, randomized, placebo-controlled study was initiated to examine whether estrogen replacement therapy had a deleterious effect on the risk of recurrence in patients with early-stage endometrial cancer. More than 1,236 women were randomized to either estrogen replacement therapy or placebo. Although the study did not complete accrual, and therefore definitive answers about the effect of estrogen replacement on survival cannot be made, some useful clinical information resulted.

The absolute recurrence rate in those taking estrogen therapy was 2.1%, which is quite low. This low rate did not differ significantly from the recurrence rate in the placebo group. It is unlikely that a randomized clinical trial will ever definitively answer the question of safety of estrogen replacement therapy in women with early-stage endometrial cancer. Therefore, the decision to use estrogen replacement therapy has to be individualized.

Estrogen replacement therapy will most likely be for the approximately one quarter of all women with endometrial cancer who are under the age of 50 and for whom surgical treatment of endometrial cancer will result in premature menopause.

Symptoms including hot flashes and night sweats can be addressed initially with agents such as venlafaxine, a serotonin and norepinephrine reuptake inhibitor.

For women whose problematic symptoms do not improve with these drugs, however, short-term estrogen may be an option. Estrogen in this setting was unlikely to significantly increase the recurrence rate of endometrial cancer, this study found.

Practice recommendations

The ACOG Committee Opinion for Hormone Replacement Therapy in Women Treated for Endometrial Cancer, Number 234, May 2000 (published before completion of this study) recommends individualization on the basis of potential benefit and risk to the patient.

It is a good recommendation, and now this study’s results can be included, as well, in discussions with patients about risks and benefits.

Surgery prevents Lynch syndrome cancers

Schmeler KM, Lynch HT, Chen L-M, Munsell MF, Soliman PT, Clark MB, Daniels MS, White KG, Boyd-Rogers SG, Conrad PG, Yang KY, Rubin MM, Sun CC, Slomovitz BM, Gershenson DM, Lu KH. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006;354:261–269.

Lu K, Broaddus R. Gynecologic cancers in HNPCC. Familial Cancer. 2005;4:249–254.

Prophylactic hysterectomy with bilateral salpingo-oophorectomy is an effective strategy for prevention of endometrial and ovarian cancer in women with the Lynch syndrome

Although ObGyns are familiar with the Hereditary Breast/Ovarian Cancer syndrome and the BRCA1 and BRCA2 genes, few are familiar with the increased risk of endometrial cancer in the Lynch syndrome, also called hereditary nonpolyposis colorectal cancer syndrome (HNPCC).

The Lynch syndrome is an inherited cancer predisposition syndrome that increases risk for endometrial cancer, colon cancer, and ovarian cancer. There are also less common cancers associated with Lynch syndrome. The genes that are responsible for inherited cancer susceptibility in families with Lynch syndrome are MLH1, MSH2, and MSH6. These genes are part of a family of genes that are responsible for repairing DNA mistakes during DNA replication. Mutations in one of the genes occur in about 1 in 1,000 individuals, which is similar in frequency to mutations in BRCA1 and BRCA2.

Women with Lynch syndrome have a 40% to 60% lifetime risk of colon cancer and a 40% to 60% risk of endometrial cancer (compare this to the 5% lifetime risk of colon cancer and 3% lifetime risk of endometrial cancer in the general population).

ObGyns can:

• Identify women who may have Lynch syndrome
• Manage their endometrial and ovarian cancer risks

The New England Journal of Medicine report helps to further define prevention strategies. Of 315 women with documented germline mutations associated with the Lynch syndrome, 61 underwent prophylactic hysterectomy and were matched with 210 women who did not undergo hysterectomy.

Key results

• None of the women who underwent prophylactic hysterectomy developed endometrial cancer, whereas 69 women in the control group (33%) developed endometrial cancer.
• None of the women who underwent bilateral salpingo-oophorectomy developed ovarian cancer, whereas 12 women in the control group (5%) developed ovarian cancer.

Practice recommendations

• These findings suggest that prophylactic hysterectomy with bilateral salpingo-oopherectomy is an effective strategy for preventing endometrial and ovarian cancer in women with the Lynch syndrome.
• For endometrial and ovarian cancer screening, the available studies have shown that measurement of the endometrial stripe is unlikely to be effective.
• Current consensus group recommendations advise an annual endometrial biopsy and a transvaginal ultrasound to examine the ovaries.
• For colon cancer screening, a colonoscopy every 1 to 2 years is recommended.