Endometrial Cancer; Clinical Aspects and Prognosis

Victor Manuel Vargas Hernandez¹* and Victor Manuel Vargas Aguilar²

¹Department of Gynecology, Hospital Juarez of Mexico, USA

²Oncology Hospital, CMN XXI century, Mexican Social Security Institute, USA

*Corresponding author: Victor Manuel Vargas Hernandez, Department of Gynecology, Hospital Juarez of Mexico, Insurgentes Sur 605-1403, Col. Napoles, 03810 DF Mexico, USA

Received: July 11, 2015; Accepted: November 11, 2015; Published: November 13, 2015

Abstract

In developed countries, endometrial cancer is common and is the second most common cancer in women; the lifetime risk of developing endometrial cancer is 2.6% and the average age at diagnosis is 61 years; 68% are diagnosed at an early stage; It manifests with abnormal uterine bleeding, especially in postmenopausal women; Risk factors are related to the effects of estrogen; reducing the risk with oral contraceptives, there are no screening tests; The treatment is surgical and minimally invasive surgery improves morbidity and mortality.

Keywords: Epidemiology; Symptoms; Risk Factors; Prognostic Indicators; Types of Endometrial Cancer

Epidemiology

Worldwide 288,000 women are diagnosed with cervical cancer [1,2], it is the most common gynecologic cancer in developed countries, with an incidence of 5.9 to 12.9 per 100,000 women and mortality rate [3] of 2.4 per 100,000. The mortality rate was 1.7 to 2.4 per 100,000 women; United States (US), is the most common gynecologic cancer; with 50,000 new cases and 8,600 deaths each year [1,2]; with incidence of 23.9 per 100,000 women [4-7], is presented at a mean age at diagnosis of 61 years and age is (20-34yrs); 1.5%, (35- 44yrs); 6% (45-54yrs ); 19% of (55-64yrs); 32.6% of (65-74yrs); 22.6%; (75 to 84yrs); 13.5% 85 years of age or older; 4.8%; from the (50-70 yrs) women have a 1.4% risk of being diagnosed with uterine cancer and risk for life in US is 2.6%; 68% are diagnosed at an early stage, the uterus located [8,9]; advanced stage with spread to regional lymph nodes and organs (20%); and distant metastases (8%). Survival rates for localized [5], and loco regional and metastatic spread are 96 %, 67%, and 17%, respectively [8,9].

Classification

Based on clinical features, pathological features, molecular genetics, incidence, response to estrogen and prognosis, the endometrial cancer could be classified as the following; there are two types of endometrial cancer [8-10 ]:

Type I endometrial cancer include endometrioide grade 1 or 2; they comprise 80%; have favorable prognosis, they are estrogen-dependent and are preceded by endometrial intraepithelial neoplasia (complex atypical endometrial hyperplasia).
Type II endometrial cancer represent 10 to 20%; They are grade 3 endometrioide or not endometrioide histopathology; clear, serous, mucinous, squamous, transitional, and mesonephric cell undifferentiated cells; They are high grade, poor prognosis without association to estrogen stimulation without precursor lesion.

Women with endometrial cancer are obese associated with chronic diseases and have higher surgical risk; robotic surgery compared with classic and laparoscopic surgery have better prognosis for surgical staging; no differences in rates of recurrence and death, but with better postoperative quality of life. The survival rate is 86% for classical radical surgery and 90% for laparoscopic and robotic surgery in patients of the same age, body mass index, associated chronic diseases, number of previous surgeries. Classical surgery has more complications compared with robotic surgery (26 vs 6.4%, p <0.001) [11].

Clinical Presentation

Abnormal uterine bleeding is the main symptom of endometrial cancer 65-90%, occasionally detected in cervical cytology screening [1- 3,12]. It is most common in postmenopausal women. The suspected presence of endometrial neoplasia (endometrial hyperplasia or carcinoma neoplastic) depends on the symptoms, age and presence of risk factors [1-3,12]. The amount of bleeding is not correlated with the risk of cancer.

Risk Factors

The main risk factor for type I endometrial cancer is prolonged exposure to excessive endogenous or exogenous estrogen without progestin right opposition [8]. Other risk factors include obesity, nulliparity, diabetes mellitus and hypertension, see Table 1; exogenous estrogen exposure includes estrogen replacement therapy after menopause and tamoxifen, whereas the endogenous exposure results from obesity, chronic anovulation, and estrogen-secreting tumors [8].

Table 1: Endometrial cancer classification.




  
    TYPE I 
    TYPE II 
    TYPE III (Family) 
  
  
    Under differentiated or degree
      <Depth of invasion
      It develops HE
      Perimenopausal
      Estrogen dependent
      Reproductive age
      Obese 
    High-grade or
      undifferentiated
      > Depth of invasion
      Papillary serous cells or clear
      endometrial atrophy
      lower weight
       
    Lynch syndrome II
      HNPCC
  
  
     
      HNPCC: Hereditary Nonpolyposis    Colorectal Cancer



Table 1:  Endometrial cancer classification.

Estrogen therapy alone in women with a uterus increases the risk of endometrial hyperplasia or cancer. Endometrial hyperplasia is identified in 20-50% of women after a year with estrogen therapy alone [13-15]; and the relative risk is 1.1 to 15% for endometrial cancer [8,9]; therapy with estrogen and progestin reduces the risk [8,9]. Tamoxifen use increases the risk of endometrial cancer in postmenopausal women [16,17]. Tamoxifen is a selective estrogen receptor modulator with both agonist and antagonist properties, depending on individual target organ and circulating serum estrogen levels [8,9]. In breast tissue, is blocks estrogen stimulation and is used for prevention and treatment.

Tamoxifen endometrial activity seems to depend on menopausal status, dose and duration [8,9]. In general, the risk increased with increasing tamoxifen (rate ratio 2.40) [8,9].

The effect of phytoestrogens on the risk of endometrial carcinoma is controversial [18-21]. Phytoestrogens are nonsteroidal compounds that occur naturally in many plants, fruits and vegetables and have both estrogenic and anti estrogen properties [8,9].

Excess endogenous estrogen is chronic anovulation or excessive endogenous conversion of androstenedione to estrone and estradiol by fat cells in obese women [9]. Estrogen-secreting tumors are rare, but can also result in endometrial carcinoma. Anovulation is common during menarche and the menopausal transition. Polycystic ovary syndrome is the most common endocrine disorder associated with anovulation. Thyroid dysfunction and elevated prolactin levels are common endocrine disorders associated with anovulation. Obese women are more likely to develop endometrial cancer; each increase in body mass index (BMI) of 5kg / m2 incurred a significantly higher risk of developing endometrial carcinoma (RR 1.59, 95% CI 1.50 to 1.68) [22]. Body Mass Index (MBI) also higher is associated with the development of endometrial carcinoma at an early age (<45 years) [9]. Unlike other disorders, however, the risk of developing endometrial carcinoma unrelated to the distribution of adipose tissue [8,9,22]. Obese women may also have other endocrine abnormalities. They may have lower circulating levels of sex hormone binding globulin (leading to increased activity of the steroid hormone), alterations in the concentration of factor insulin-like binding proteins and growth, and resistance to insulin, all of which may contribute to the increased risk of endometrial carcinoma in these women [8,9]. Women with severe obesity (=40 kg / m2) who develop endometrial cancer are more likely than women with a BMI <30kg/m2 for a less aggressive histologic subtype (endometrioide: 87% versus serous or clear cell: 75%) [9]. Severe obesity is also associated with an increased risk of death [23] obese premenopausal women, especially those with PCOS, are often also anovulatory.

The age of early menarche and late menopause are risk factors [8,9]. Both factors result from prolonged estrogen stimulation in reproductive years during which anovulatory cycles are common.

Some producers mainly estrogen ovarian tumors granulosa cells are associated with endometrial neoplasia. Endometrial biopsy endometrial hyperplasia detected in 25 to 50% of women with tumors and carcinoma of [8,9] granulosa cells in 5 to 10%. Endometrial adenocarcinomas are associated with tumors of granulosa cell-stromal are generally early stage and well differentiated [8,9]. Endometrial cancer occurs in postmenopausal women and in lower under 50 years who develop endometrial cancer often have risk factors such as obesity or chronic anovulation [8,9].

The family tendency toward endometrial carcinoma in first grade [24], although there are no genes identified consistently. Women with Lynch (Lynch syndrome) syndrome have an increased risk of developing endometrial cancer and are likely to develop the disease at an early age; also, they run a high risk of colon cancer and ovarian cancer, along with other malignancies. Lynch syndrome is an autosomal dominant disorder that is caused by a germline mutation in one of several DNA repair genes, accounting for 2-5% of all endometrial carcinomas [8,9,25,26], women with this syndrome, have a risk of endometrial cancer of 27-71% compared to 2.6% of the general population and is considered a type 3 of endometrial cancer; It is a genetic or hereditary cancer that has a partnership or is part of Lynch II syndrome, Hereditary Nonpolyposis Colo. Rrectal Cancer (HNPCC); genetic disease is 10% and 5% represents Lynch II syndrome; BRCA1 mutations are associated with endometrial carcinoma; BRCA1 mutation significantly increases the risk of uterine cancer (RR 2.65; 95% CI: 1.69 to 4.16) and higher only for BRCA mutation carriers who take tamoxifen, with increased risk of serous carcinoma endometrium in BRCA carriers [8,9].

Women with Cowden syndrome, an autosomal dominant disorder where there is a mutation in the tumor suppressor gene PTEN, have characteristics mucocutaneous lesions, have a higher prevalence of uterine leiomyomas and endometrial cancer, breast, thyroid, kidney and colorectal. They are rare this rare syndrome; but lifetime risk of endometrial cancer [27-29] 13-19% is reported.

The association between increased consumption of sugars and endometrial cancer are mainly reported in obese; there is no overall association between alcohol consumption and endometrial cancer (RR 1.04, 95% CI 0.91 to 1.18) [8,9].

Associated Factors

The risk of endometrial cancer is not related to parity [8,9]; nulliparity and infertility are not considered independent risk factors; However, the association of women and infertile anovulatory cycles; Women with type 2 diabetes mellitus and hypertension are at increased risk of endometrial carcinoma [30]. Other factors, especially obesity, increased risk represent independent effects [31]; diets rich in carbohydrates, hyper-insulinemia, insulin resistance, and elevated levels of factors insulin-like growth plays a role in the development of endometrial cancer [8,9].

Protective Factors

The use of oral contraceptives reduces the risk of endometrial cancer (> 50%) and persists for 10 to 20 years after stopping [32,33]. Having a first child at late reproductive age, the lower the risk of endometrial cancer [34,35]; smoking reduces the risk by hepatic metabolic clearance of estrogen; sedentary lifestyle contributes to the development of cancer and reduces physical activity; obesity central adiposity, causes immunological, metabolic, functional changes in hormone levels, and growth factors, which favors the development endometrial cancer [36].

The reduced risk of endometrial cancer is proportional to the amount of coffee and tea consumed [37-40]; the use of calcium supplements and aspirin are associated with lower risk of endometrial cancer mainly in obese [41,42].

Prognostic Indicators of Endometrial Cancer

Risk factor for recurrence of endometrial cancer is dividide d in uterine and extra-uterine factors. Uterine factors include histological type, grade, depth of invasion, myometrial, cervical involvement, vascular invasion, presence of atypical endometrial hyperplasia, hormone receptor status and ploidy and S-phase fraction ectopic adnexal factors include commitment, intraperitoneal metastases, positive peritoneal cytology, and metastasis to pelvic and para-aortic lymph nodes. Patients without evidence of extrauterine disease without cervical involvement and no evidence of vascular invasion have a low risk of recurrence generally women with evidence of extrauterine disease, cervical involvement or vascular invasion are a high risk group. If one of these three factors is positive, the recurrence rate is 20% increasing to 43% for two positive factors and 63% for three factors 8.9.

Conclusions

Endometrial cancer is the histopathological diagnosis is performed on the sample of endometrium; no routine screening tests are performed only in those patients with Lynch syndrome, who have lifetime risk of endometrial cancer, 27-71% compared with 3% in the general population. The detection and prevention of endometrial cancer in these women include endometrial sampling and prophylactic hysterectomy.

References

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Citation: Hernandez VMV and Aguilar VMV. Endometrial Cancer; Clinical Aspects and Prognosis. Austin J Womens Health. 2015; 2(2): 1016.

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