In 2006, a European workshop of 21 experts in the treatment of hereditary gastrointestinal cancers from ninecountries (the Mallorca group) recommended the following endometrial cancer surveillance strategy for patients with HNPCC or Lynch II syndrome: annual pelvic examination, transvaginal ultrasound, and endometrial biopsy beginning at 30 to 35 years of age (53). These recommendations are by expert opinion only, and it is unknown whether these interventions are cost-effective or will impact mortality from endometrial or ovarian cancer in patients with Lynch II syndrome. An attractive alternative to early detection is prophylactic surgery after completion of childbearing (54,55). In 2006 a multi-institutional, matched case-control study found that prophylactic hysterectomy withbilateral salpingo-oophorectomy is an effective primary prevention strategy in women with Lynch II syndrome (51). No woman with hysterectomy and bilateral salpingo-oophorectomy developed endometrial, ovarian, or primary peritoneal carcinoma during the period of follow-up. In contrast, endometrial cancer developed in 33% and ovarian cancer in 5% of women who did not undergo prophylactic surgery (51).
There are rare reports of pedigrees in which family members are affected by endometrial cancer alone, and genetic studies have not found a germline mutation associated with site-specific endometrial cancer (42,56,57). A population-based study of endometrial cancer and familial risk in younger women (Cancer and Steroid Hormone, or CASH, Study Group) reported that a history of endometrial cancer in a first-degree relative increased the risk of endometrial cancer by nearly threefold (odds ratio of 2.8; 95% confidence interval [CI], 1.9–4.2) (58). A significant association was found with colorectal cancers, with an observed odds ratio of 1.9 (95% CI, 1.1–3.3). The presence of Lynch II syndrome families within the cohort may explain the latter association, but a family history of endometrial caner was an independent risk factor for endometrial cancer, after adjusting for age, obesity, and number of relatives (58).
Endometrial cancer and breast cancer share some of the same reproductive and hormonal risk factors such as nulliparity and exposure to unopposed estrogen (4,8,59–63). However, the familial association between breast and endometrial cancer is still uncertain and studies report conﬂicting results (63–67). For example, in the past it was thought that patients with BRCA mutations were at elevated risk for endometrial cancer, in addition to breast and ovarian cancer. A study suggests that this increase in risk is seen only in those patients with a personal history of breast cancer who are taking tamoxifen (68).