A Guide to Endometrial Cancer

Endometrial cancer is the second most common gynaecological cancer worldwide, and the most common in developed countries. In developing countries, cervical cancer remains the most common cancer of the female reproductive tract. However, unlike cervical cancer, which is declining in incidence across many countries, mainly due to an increased awareness of pap screening and the development of the HPV vaccine; the incidence rates of endometrial cancer are steadily increasing.

Symptoms

The main symptom of endometrial cancer is abnormal vaginal bleeding. This may be bleeding that occurs between your periods if you are premenopausal, or any sort of bleeding if you are postmenopausal. There are a number of reasons why you may be experiencing abnormal bleeding, but you should always consult a doctor to make sure that it is nothing serious. Other, less common, symptoms of endometrial cancer are abdominal pain and discomfort after sexual intercourse.

Risk factors

Approximately 75% of endometrial cancers are oestrogen-dependent, arising as a result of chronic stimulation of the endometrium by oestrogen. The excess of oestrogen causes the cells of the endometrium to divide, unopposed by progesterone, which normally moderates the effects of oestrogen. Historically, endometrial cancer was considered to be predominantly a postmenopausal condition; associated with erratically fluctuating hormone levels. However, it is becoming increasingly prevalent in pre-menopausal women of childbearing age, probably due to a strong association with obesity, which, globally, is increasing in prevalence. Furthermore, women with metabolic conditions, such as PCOS, may also be at higher risk due to the link between PCOS and Obesity. Other aspects of PCOS may put women at a higher risk, such as unopposed oestrogen (due to low progesterone in PCOS) but more research is needed to support this. 

Starting your periods late, or going through the menopause early, both of which result in a shorter menstrual lifespan, are both associated with a lower risk of developing endometrial cancer. Giving birth has also been shown to confer a degree of protection against development of endometrial cancer; with an increasing number of full term pregnancies associated with enhanced protection. Taken together, this suggests that those women who have experienced fewer overall years of menstruating, are at lower risk of developing endometrial cancer. Conversely, those with a higher lifetime exposure to oestrogens, for example those who start their periods at a young age, or never give birth, might have a higher risk of endometrial cancer. However, to date that work is inconclusive and needs further validation. 

Another possibility is that cancer rates have risen in recent years, coinciding with an earlier age of menarche, as a result of environmental hormonal and/or physiological disruptions. These are associations that still need to be explored, but are worth investigating.

Hormone Replacement Therapy (HRT) and Tamoxifen treatment both increase the risk of endometrial cancer. Oestrogen-only HRT will usually only be prescribed to those women who have already undergone a hysterectomy. Those who still have their uterus will preferentially be given a combination of oestrogen and progesterone, as the latter hormone confers protection against too much oestrogenic activity. Tamoxifen is generally used as a highly effective treatment for breast cancer. You should always speak to your doctor prior to deciding whether or not to take Tamoxifen because the benefits of taking it usually outweigh the slightly increased risk of developing endometrial cancer.  

Endometrial cancer also has a familial component and if your mother, or a close family member, has been diagnosed with the condition, your risk will be higher. Those diagnosed with Lynch syndrome, which is also known as hereditary nonpolyposis colorectal cancer (HNPCC), have a higher risk of developing various cancers, including endometrial cancer. With certain Lynch Syndrome gene mutations, the lifetime risk of developing endometrial cancer is as high as 40-60%.     

Treatment and prognosis

The usual treatment for endometrial cancer is to undergo surgical removal of the uterus, known as a hysterectomy. The ovaries and fallopian tubes will probably be removed at the same time to avoid the risk of the cancer spreading to these areas. Depending on the stage and grade of the cancer, your doctor may also recommend a course of chemotherapy and/or radiotherapy to destroy any remaining cancer cells.

If endometrial cancer is diagnosed early (stage I), the five year survival rates are thought to be as high as 92%. However, if diagnosed at stage IV, five year survival rates fall to between 20 and 26%. This highlights the value of early diagnosis. Atypical Endometrial Hyperplasia ( AEH) is often a precursor of endometrial cancer. It usually precedes endometrial cancer by several years, thus, prompt diagnosis of AEH gives a critical window of opportunity for preventative action and/or close monitoring of women considered to be at high risk.

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Sources:

• Committee on Gynecologic Practice. “Tamoxifen and Uterine Cancer.” ACOG, June 2014, www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/06/tamoxifen-and-uterine-cancer. 
• Dossus, Laure, et al. “Reproductive Risk Factors and Endometrial Cancer: the European Prospective Investigation into Cancer and Nutrition.” International Journal of Cancer, vol. 127, no. 2, 15 July 2010, pp. 442–451., doi:10.1002/ijc.25050.
• Ginsburg, Ophira, et al. “The Global Burden of Women’s Cancers: a Grand Challenge in Global Health.” The Lancet, vol. 389, no. 10071, 25 Feb. 2017, pp. 847–860., doi:10.1016/s0140-6736(16)31392-7.
• Manna, P.r., et al. “Dysregulation of Aromatase in Breast, Endometrial, and Ovarian Cancers.” Progress in Molecular Biology and Translational Science Molecular and Cellular Changes in the Cancer Cell, vol. 144, 2016, pp. 487–537., doi:10.1016/bs.pmbts.2016.10.002.
• Murali, Rajmohan, et al. “Classification of Endometrial Carcinoma: More than Two Types.” The Lancet Oncology, vol. 15, no. 7, June 2014, pp. e268–e278., doi:10.1016/s1470-2045(13)70591-6.
• Sanderson, Peter A., et al. “New Concepts for an Old Problem: the Diagnosis of Endometrial Hyperplasia.” Human Reproduction Update, vol. 23, no. 2, 1 Mar. 2017, pp. 232–254., doi:10.1093/humupd/dmw042. 
• “Womb Cancer.” Risks and Causes | Womb Cancer | Cancer Research UK, 6 Sept. 2017, https://www.cancerresearchuk.org/about-cancer/womb-cancer/risks-causes.
• “Womb (Uterus) Cancer: Overview.” NHS Choices, NHS, https://www.nhs.uk/conditions/womb-cancer/.