Bereks - Uterine Cancer

• Endometrial carcinoma is the most common malignancy of the female genital tract, accounting for almost one-half of all gynecologic cancers in the United States
• In 2018, an estimated 63,230 new cases and 11,350 cancer-related deaths are anticipated
• Endometrial carcinoma is the fourth most common cancer, ranking behind breast, lung, and colorectal cancers, and the sixth leading cause of death from malignancy in women
• Overall, about 2.8% of women develop endometrial cancer during their lifetimes
• Endometrial cancer is a disease that occurs primarily in postmenopausal women and is increasingly virulent with advancing age
• Type I endometrial cancer


  Occurs in younger, perimenopausal women with a history of exposure to unopposed estrogen, either endogenous or exogenous. Tumors begin as hyperplastic endometrium and progress to carcinoma. These "estrogen-dependent" tumors tend to be better differentiated and have a more favorable prognosis than tumors not associated with hyperestrogenism
• Type II endometrial cancer


  Occurs in women without estrogenic stimulation of the endometrium. These spontaneously occurring cancers are not pathologically associated with endometrial hyperplasia, but may arise in a background of atrophic endometrium. They are less differentiated and associated with a poorer prognosis than estrogen-dependent tumors. These "estrogen-independent" tumors tend to occur in older, postmenopausal, thin women and are present disproportionately in African American and Asian women
• Risk factors for endometrial cancer

  • Nulliparity
  • Late menopause
  • Obesity
  • Diabetes mellitus
  • Unopposed estrogen therapy
  • Tamoxifen therapy
  • Atypical endometrial hyperplasia
  • Lynch II syndrome
• Endometrial hyperplasia


  Represents a spectrum of morphologic and biologic alterations of the endometrial glands and stroma, ranging from an exaggerated physiologic state to carcinoma in situ
• Types of endometrial hyperplasia

  • Simple (cystic without atypia)
  • Complex (adenomatous without atypia)
  • Atypical simple (cystic with atypia)
  • Atypical complex (adenomatous with atypia)
• The risk of endometrial hyperplasia progressing to carcinoma is related to the presence and severity of cytologic atypia
• 25% to 43% of patients with atypical hyperplasia detected in an endometrial biopsy or curettage specimen will have an associated, usually well-differentiated, endometrial carcinoma detected during hysterectomy
• Fertility-sparing treatment of endometrial hyperplasia and cancer


  Nonsurgical treatment with hormonal therapy may be an option for appropriately selected women desiring to preserve fertility. High regression rates for endometrial cancer and atypical hyperplasia following treatment with progestin therapy are extensively documented
• Progestational therapy can successfully treat disease while preserving fertility for patients with atypical hyperplasia and well-differentiated presumed stage I endometrial cancer
• Only 1 month of progestational treatment was required to achieve a response in the 76% of patients without recurrence
• Twenty patients achieved pregnancy following treatment
• 24% (19/81) of the original cohort never responded to treatment, and only 68% had any documented follow-up endometrial sampling
• Progestational therapy


  Can successfully treat disease while preserving fertility for patients with atypical hyperplasia and well-differentiated presumed stage I endometrial cancer
• Appropriate patient selection and exclusion criteria remain undefined
• Patients must be counseled that failure to identify recurrence or extension of disease during progestational treatment may lead to a delay in definitive surgery and ultimately a compromised prognosis
• Continuous progestin therapy with megestrol acetate (40 to 160 mg per day)


  Probably the most reliable treatment for reversing complex or atypical hyperplasia, recognizing that higher doses may be associated with reduced compliance secondary to side effects
• No clear consensus exists for an optimal follow-up interval
• Therapy should be continued for at least 3 to 6 months, and endometrial biopsy should be performed to assess response
• Periodic endometrial biopsy or transvaginal ultrasonography is advisable in patients being monitored on progestin therapy for atypical hyperplasia because of the presence of undiagnosed cancer in at least 25% of cases and the high recurrence rate after treatment with progestins
• In this setting the use of progesterone should be considered a temporary, rather than long-term, treatment
• For women with atypical complex hyperplasia who no longer desire fertility, hysterectomy is recommended
• Screening for endometrial cancer should not be undertaken because of the lack of an appropriate, cost-effective, and acceptable test that reduces mortality
• Routine Papanicolaou (Pap) testing is inadequate, and endometrial cytologic assessment is too insensitive and nonspecific to be useful in screening for endometrial cancer, even in a high-risk population
• Transvaginal ultrasonographic examination of the uterus and endometrial biopsy are too expensive to be employed as screening tests
• Screening for endometrial cancer or its precursors may be justified for certain high-risk women, such as members of families with hereditary nonpolyposis colorectal cancer
• Women taking tamoxifen receive no benefit from routine screening with transvaginal ultrasonography or endometrial biopsy
• There is insufficient evidence to recommend screening for endometrial cancer in women because of a history of unopposed estrogen therapy, late menopause, nulliparity, infertility or failure to ovulate, obesity, diabetes, or hypertension
• Most patients with endometrial cancer present with abnormal perimenopausal or postmenopausal uterine bleeding when the tumor is still confined to the uterus
• Application of an appropriate and accurate diagnostic test in this situation usually results in early diagnosis and high cure rate with timely treatment
• It is important to recognize that the workup of abnormal uterine bleeding should include endometrial biopsy even in premenopausal patients, as 5% of cases are in women under the age of 40
• Most endometrial carcinomas are sporadic, but at least 10% of cases have a hereditary basis
• Two genetic models were described in the development of familial endometrial cancer: Lynch II syndrome and patients with a predisposition for endometrial cancer alone, both of which are inherited in an autosomal dominant fashion
• The majority of studies focused on the increased incidence of endometrial cancer associated with Lynch II syndrome, a highly penetrant disorder (80% to 85%)
• Lynch II syndrome is caused by an inherited mutation in one of the following mismatch repair genes: hMSH2, hMLH1, PMS1, PMS2, or hMSH6
• The lifetime risk of endometrial cancer in women with Lynch II syndrome is 32% to 60% and the lifetime risk of ovarian cancer is 10% to 12%