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Endometrial Cancer: Causes, Symptoms, Diagnosis And Treatment

Endometrial cancer is the rapid growth of cells in the endometrium (uterus lining). It is also known as uterine cancer. It's the fourth common cancer found in women [1] and around 40,000 die every year from this disease. It mostly occurs in women post-menopause, mostly when they are in their seventies.

Endometrial cancer has worse chances of survival in a 5-year period than breast or prostate cancers. In the early stages, it can be treated by hysterectomy. However, it becomes lethal in the advanced stage.

Causes Of Endometrial Cancer

The main risk factors associated [1] with uterine cancer are menopause, obesity, diabetes, unopposed oestrogen and hypertension.

1. Menopause

Women who mostly undergo postmenopausal treatment with hormones are at a higher risk of contracting uterine cancer than the rest of them. According to epidemiologic studies, frequent use of unopposed oestrogens can increase substantial risk, especially among lanky women. Hormone Replacement Therapy was widely used earlier for treating menopausal weakness, fatigue and heart disease. Nevertheless, it isn't used much these days, as it maximizes the possibility of breast cancer, blood clots and endometrial cancer. When endometrium is exposed [3] to oestrogen, without added progesterone, it can stimulate rapid cell proliferation in the uterus, hence resulting in excess oestrogen without progesterone.

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2. Obesity

Obesity [4] is a major risk factor for more than half of uterine cancer cases. Women with higher BMI are more susceptible to this cancer than the ones with normal BMI. Body fat, which is a complex endocrine gland, comprises adipocytes, preadipocytes, infiltrating macrophages, nerve, stromal and stem cells. All these combined secrete adipokines that have localized effects; it increases endometrial cell growth and can form tumours. Besides, adipose tissues in fats, also promote tumour formation, as it contains mesenchymal stem cells. More number of adipose tissues can cause aromatase activity, which converts androgens to estrogens. It can also cause hyperglycemia, which sources endometrial proliferation.

3. Diabetes

A Swedish mammography study found [5] a positive relation between diabetes and decreased physical activity. Type 2 diabetes is associated with hyperinsulinaemia. It increases oestrogen levels by simultaneously lowering the sex hormone globulin. High levels of IGF-1 and IGF- binding protein-1, have been known to cause endometrial cancer, especially in elder obese women. C-reactive protein, an inflammatory biomarker [6] increases by insulin resistance, which is caused during diabetes, thus increasing the chances of uterine cancer post menopause.

4. Hypertension

Although the relation between hypertension [7] and endometrial cancer isn't significant, it can be attributed to factors like lifestyle changes, medical conditions revolving around diet, less exercise, BMI and diabetes. Hypertension inhibits apoptosis; it can also be related to hysterectomies, which has the potential to bias the risk analysis. The medications used to cure anxiety can increase the risk of cancer.

There are also other reasons that can be involved.

  • Use of tamoxifen to prevent the occurrence of breast cancer
  • Suffering from metabolic syndrome
  • Estrogen produced by the body, reaching the endometrium tissue. The following can be the reasons: unable to give birth, early menstruation, late menopause and suffering from polycystic ovary syndrome.
  • A family history of uterine cancer in mother or sister.
  • Genetic conditions like Lynch syndrome
  • Suffering from endometrial hyperplasia

Symptoms Of Endometrial Cancer

Mostly the signs and symptoms are accompanied by abnormal vaginal bleeding or pelvic region pain. One should immediately consult the doctor on observing such signs.

  • Any bleeding or discharge from the vagina that is not related to periods.
  • Vaginal bleeding, despite the occurrence of menopause
  • Pain or difficulty while urination
  • Painful sex
  • Soreness or pain in the pelvis

Diagnosis Of Endometrial Cancer

Usually, endometrial cancer is not detected easily in the Pap test, as the cell growth starts in the uterus. To find out the signs, a uterus tissue should be removed and examined under a microscope, to confirm cell growth [9] . The following methods can be used for the purpose:

  • Endometrial biopsy: A thin and flexible tube is inserted via cervix, into the uterus. This scrapes off a small quantity of endometrium tissue and then collects the tissue samples.

Dilatation and curettage: The process is also called D&C; the cervix is dilated enough so that a spoon-shaped instrument, called curette, could be inserted inside for tissue removal. Later the tissues are checked for the sign of cancer.

  • Hysteroscopy: A hysteroscope which is a thin, tube kind of instrument is inserted via vagina and cervix, into the uterus lining. It also has a light and lens to check for viewing inside endometrium, and also a tool to gather tissue sample.
  • Other tests to diagnose the disease [9] are given below.

    • The patient is also given a thorough physical test to see the general signs of health, any past record of illness, addictions, any unusual lumps in the body, etc.
    • Transvaginal ultrasound, a process to detect any anomaly in the vagina, fallopian tubes, uterus and bladder helps to create an image of internal tissues, by using ultrasound waves. The image is called sonogram, and it proves effective to identify any tumour formation.

    Post Cancer Diagnosis

    This usually involves a thorough check up to see if cancer is limited to uterus [9] or has spread to other body parts. This process is called staging and the treatment is decided on the basis of cancer stage. Cancer first spreads through tissues, then it starts travelling through lymph vessels and bloodstream. When the disease starts escalating through lymph, it's called metastasis.

    Endometrial cancer has been divided into four stages.

    • Stage I: involves the spread in the endometrium, and gradually myometrium.
    • Stage II: Cancer grows into the connective tissue of the cervix, but not outside the uterus.
    • Stage III: The disease has spread inside uterus and cervix, in the entire pelvic region, but not beyond.
    • Stage IV: Involves the spread in the gallbladder, bowel system, abdomen and maybe lymph nodes in the groin.

    Stage 3 and 4 come under high-risk treatment.

    In the initial stages of cancer, hysterectomy is used to detect cancer. An operation is done for removal of the uterus. A thorough examination of the vagina, fallopian tubes, cervix, ovaries and rectum is done using the Pap test. The nurse/ doctor inserts two lubricated fingers, of first hand inside the vagina and another hand over the lower abdomen to detect the placement, shape and size of ovaries and uterus. Also, a gloved finger is put inside the rectum to figure out any lump growth or abnormality.

    Treatment Of Endometrial Cancer

    Presently, five types of treatments are available [8] for this type of cancer:

    1. Surgery

    It is the most common treatment used to cure cancer. The following methods can be used while surgery:

    • Total hysterectomy: It includes removal of uterus along with cervix. If they are taken out through the vagina, it's called vaginal hysterectomy. When taken out through large cut made in the abdomen, the operation is termed abdominal hysterectomy. Similarly, laparoscopic hysterectomy involves using a laparoscope, to make a small cut made in the abdomen.
    • Bilateral salpingo-oophorectomy is the operation to remove uterus as well as fallopian tubes.

    Radical hysterectomy takes out a small part of the vagina, along with uterus and cervix. If required, even ovaries, lymph nodes or fallopian tubes can be discarded.

    Lymph node dissection involves removal of lymph nodes surrounding the pelvic region, to check for symptoms of cancer.

    Post-surgery, the patient is given adjuvant therapy, which is to minimize the chances of cancer returning back to the source. Hormone treatment or radiation therapy might be used to eradicate the leftover cancer cells fully.

    2. Radiation therapy

    This therapy involves the use of powerful X-rays or other forms of radiation to eliminate cancer cells or curb their growth.

    • External radiation therapy uses a machine externally to project radiation waves toward cancer.
    • Internal radiation therapy uses needles, wires, seeds or catheters that are radioactive; they are directly placed nearby the cancer cells.

    These therapies can also be used to provide relief from symptoms and give a healthier life.

    3. Chemotherapy

    Chemotherapy is effective in cancer treatment, by using drugs to either kill or inhibit the growth of cancer cells. When the drugs can travel through blood vessels to the cells within the entire body, it's called systematic chemotherapy. The drugs can be administered orally or through muscles and veins. Regional chemotherapy is used to directly affect the cancer cells in the cerebrospinal fluid, some organ, and the abdominal cavity.

    4. Hormone Therapy

    This therapy stops the growth of tumour cells by removing hormones or preventing their flow around. Receptors, surgery, drugs or sometimes radiation is used to stop the hormones; the test results show the exact hormones that are attaching themselves to cancer cells.

    5. Targeted Therapy

    In this therapy, the cancer cells are identified and then removed, without causing any harm to normal cells. There are three types within targeted therapy, which are used to treat endometrial cancer.

    • Monoclonal antibody therapy makes use of antibodies derived from a particular type of immune cell within the system. These antibodies prove helpful in the identification of substances promoting the growth of cancer cells; they attach to these substances and eradicate cancer cells, or stop their growth. These antibodies are infused with the body, either alone, or with some drugs, receptors or radioactive chemical. Bevacizumab is used in stage 3, 4 or recurrent cancer symptoms.
    • mTOR inhibitors prevent the working of a protein called mTOR, which controls the cancer cells division, and formation of tumours, new blood vessels. Everolimus and ridaforolimus are the frequently used mTOR inhibitors.
    • Signal transduction inhibition is an effective method to stop the signals sent from one molecule to another, to stop cancer cells from functioning. Metformin is immensely effective during the last stages of cancer.

    Endometrial cancer cannot be prevented completely, but sure minor lifestyle changes can lower the risk factors. A healthy lifestyle should be maintained, with consumption of timely diet. Less smoking, drinking can help reduce hypertension. Keeping a balanced diet and light exercise minimizes the chances of obesity and diabetes. Regular monthly health check-ups, even of vagina and uterus can assist in keeping track. If cancer is detected in early stages, it is much easier to completely get rid of it.

    View Article References
    1. [1] Leslie, K. K., Thiel, K. W., Goodheart, M. J., De Geest, K., Jia, Y., & Yang, S. (2012). Endometrial cancer. Obstetrics and gynaecology clinics of North America, 39(2), 255-68.
    2. [2] Ali AT. (2013). Risk factors for endometrial cancer. Ceska Gynekol. 78(5), 448-459.
    3. [3] Brinton, L. A., & Felix, A. S. (2013). Menopausal hormone therapy and risk of endometrial cancer. The Journal of steroid biochemistry and molecular biology, 142, 83-89.
    4. [4] Onstad, M. A., Schmandt, R. E., & Lu, K. H. (2016). Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 34(35), 4225-4230.
    5. [5] Lucenteforte, E., Bosetti, C., Talamini, R., Montella, M., Zucchetto, A., Pelucchi, C., Franceschi, S., Negri, E., Levi, F., … La Vecchia, C. (2007). Diabetes and endometrial cancer: effect modification by body weight, physical activity and hypertension. British journal of cancer, 97(7), 995-8.
    6. [6] Hye Joung, K., Jeong, J., & Ku., B. J. (2015). The Association between Type 2 Diabetes Mellitus and Women Cancer: The Epidemiological Evidences and Putative Mechanisms. BioMed Research International.
    7. [7] Aune, Dagfinn & Sen, Abhijit & J Vatten, Lars. (2017). Hypertension and the risk of endometrial cancer: A systematic review and meta-analysis of case-control and cohort studies. Scientific Reports. 7. 44808.
    8. [8] Endometrial Cancer Treatment (2018). PDQ Cancer Information Summaries Bethesda (MD): National Cancer Institute (US)
    9. [9] Denschlag, D., Ulrich, U., & Emons, G. (2011). The diagnosis and treatment of endometrial cancer: progress and controversies. Deutsches Arzteblatt international, 108 (34-35), 571-577.
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    Story first published: Thursday, December 27, 2018, 13:15 [IST]