Endometrial cancer

Endometrial cancer refers to tumours that originate in the endometrial lining of the uterus (not the uterus itself, a muscle). Endometrial cancer is the most common form of uterine cancer – more than 90 per cent.

Endometrial cancer occurs more commonly in postmenopausal women, and signs are often investigated early, resulting in reasonable survival rates.

Ninety per cent of endometrial cancers are thought to be sporadic and the rest hereditary.​1,2​ Endometrioid carcinomas make up about 80 per cent of endometrial cancers and are usually a result of a mutation in the PTEN gene.​3​

Symptoms of endometrial cancer

  • Vaginal bleeding in postmenopausal women​4​
  • Metrorrhagia in premenopausal women (bleeding between periods, irregular bleeding)
  • Discharge may come before bleeding
  • A Pap test revealing endometrial cells in postmenopausal women
  • Atypical Pap test result in any woman
  • Feeling a pelvic mass
  • Unexplained weight loss
  • Pain that is not necessarily specific due to tumour growth – back, pelvis, urinating, sex,
  • Non-specific symptoms like bloody stools, weight loss, bloody urine

Outcomes of endometrial cancer

In Australia, this cancer is found in one in 80 women by the age of 70 – that is, 1,400 diagnoses every year, out of which about 260 will die. In the United States, incidence rates are higher, with endometrial cancer affecting one in every 50 women.

In 2013, 49,560 women were diagnosed and out of those women, 8,190 women die. Higher grade tumours, more advanced age, and more extensive spread all have worse outcomes. Over 60 per cent of all patients are cancer-free five years post-treatment. ​5​     

Average five-year survival rates:

  • Stage I or II – 70-95 per cent survival rates
  • Stage III or IV – 10-60 per cent survival rates

Who gets endometrial cancer?

Many of the risk factors for endometrial cancer involve the hormone oestrogen. For examplem, in premenopausal women, a dominance of oestrogen in relation to progesterone increases risk of endometrial cancer. It is important to remember not all women with endometrial cancer appear to have known risk factors.​6–8​

  • It most commonly occurs in women aged 50-70
  • 20 per cent of endometrial cancers are found in premenopausal women, with five per cent of those under 40
  • Overweight women – lack of exercise, high energy intake, high fat calories
  • Women with unopposed oestrogen (low or no progesterone)
  • Those without regular ovulation (anovulatory cycles or amenorrhoea)
  • Developed countries with diets high in fat have more endometrial cancer
  • Use of tamoxifen (part of some breast cancer treatments) may increase incidence (especially in use for over five years)
  • Women with high blood pressure and diabetes
  • Previous pelvic radiation therapy
  • Women on oestrogen-only and oestrogen plus progestin hormone therapy
  • Women with endometrial hyperplasia
  • Women without their own children (pregnancies) (called nulliparity – never bore children)
  • Women who had their first period at an early age and had a late menopausal age (long ovulation span)
  • Some women with Polycystic ovarian syndrome (PCOS)
  • Family or personal history of breast or ovarian cancers
  • A family history of hereditary nonpolyposis colorectal cancer or (in first-degree relatives) endometrial cancer

 Protective factors

  • Oral contraceptive pill (OCP) use​9​
  • Multiple pregnancies
  • Breastfeeding​10​
  • Prophylactic hysterectomy and oophorectomy (removal of uterus, cervix, and ovaries)
  • Exercise and healthy weight

Types of endometrioid cancers

  • Adenocarcinoma – usually younger women, good prognosis except when late age or stage​11​
  • Adenosquamous carcinoma – glandular and squamous cells, poor prognosis​12​
  • Adenoacanthoma – benign squamous cells, glandular cells are cancerous
  • Mixed cell adenocarcinoma – more than one type of endometrial cancer, 10 per cent of all endometrial cancers​13​
  • Papillary serous adenocarcinoma – 10 per cent of endometrial cancers, tends to be aggressive, more likely to metastasise, like ovarian cancers, often late detection, poor prognosis​14​

Non-endometrioid and rare endometrial cancers

  • Clear cell adenocarcinoma – 4-5 per cent of all endometrial cancers, tends to be aggressive, more likely to metastasise, often late detection, usually caused by women exposed to estrogenic drug diethylstilbestrol (DES) prescribed between 1938 and 1971 for preventing miscarriage, poor prognosis​15​
  • Mucinous adenocarcinoma and serous adenocarcinoma – less than one per cent of all endometrial cancers, found with genetic mutation at p53, a tumour suppression gene​16​

Prevention and screening of endometrial cancer

There are no standard screening tests for endometrial cancer, so postmenopausal women should be vigilant about bleeding – 30 per cent of postmenopausal women with vaginal bleeding have endometrial cancer.

Premenopausal women should also be very cautious about mid-cycle spotting and bleeding, though in your fertile years, this can have many other causes.

Seeing your doctor for examination if you experience any mid-cycle spotting, bleeding or abnormal discharge (any discharge that is not normal for you) helps with early detection and survival. In its early stages, endometrial cancer is very curable, so getting diagnosed quickly is beneficial.​17,18​

Stages and classifications of endometrial cancer

  1. Stage I – Tumour growth is confined to the uterus. This is then split up into Stage 1A, Stage 1B and State IC.
  2. Stage II – There is uterine and cervical involvement, but the tumours to not extend outside of the uterus. This is then split further into two more stages: Stage IIA and Stage IIB.
  3. Stage III – The tumour(s) have invaded the uterus, but not beyond the true pelvis. This is then split once again into another three stages: Stage IIIA, Stage IIIB, and Stage IIIC, depending on where it has spread.
  4. Stage IV – There is involvement of the bladder or intestines or a distant metastases, with further stages being Stage IVA and Stage IVB.

Tumour types in endometrial cancer

  • Type I – often oestrogen-responsive, diagnosed in younger, perimenopausal or obese women. Tend to be low-grade, and usually endometrioid. There may be mutations (PTEN, PIK3CA, KRAS, CTNNBI).
  • Type II – tumours usually high-grade (serous, clear-cell histology), occurring in older women. P53 mutations are found in 10-30 per cent of cases. Up to 10 per cent of all endometrial cancers are type II. Tend to recur.

Treatment

Treatment may include: ​19​

  • Surgery
  • Radiation therapy
  • Chemotherapy
  • Hormone therapy

References

  1. 1.
    Lu Y, Ek WE, Whiteman D, et al. Most common ‘sporadic’ cancers have a significant germline genetic component. Human Molecular Genetics. Published online June 18, 2014:6112-6118. doi:10.1093/hmg/ddu312
  2. 2.
    Bell D, O’Hara. The genomics and genetics of endometrial cancer. AGG. Published online March 2012:33. doi:10.2147/agg.s28953
  3. 3.
    Risinger J, Hayes K, Maxwell G, et al. PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics. Clin Cancer Res. 1998;4(12):3005-3010. https://www.ncbi.nlm.nih.gov/pubmed/9865913
  4. 4.
    Clarke MA, Long BJ, Del Mar Morillo A, Arbyn M, Bakkum-Gamez JN, Wentzensen N. Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women. JAMA Intern Med. Published online September 1, 2018:1210. doi:10.1001/jamainternmed.2018.2820
  5. 5.
    Hermens M, van Altena AM, van der Aa M, et al. Endometrial cancer prognosis in women with endometriosis and adenomyosis: A retrospective nationwide cohort study of 40 840 women. Intl Journal of Cancer. Published online December 27, 2021:1439-1446. doi:10.1002/ijc.33907
  6. 6.
    Laaksonen MA, Arriaga ME, Canfell K, et al. The preventable burden of endometrial and ovarian cancers in Australia: A pooled cohort study. Gynecologic Oncology. Published online June 2019:580-588. doi:10.1016/j.ygyno.2019.03.102
  7. 7.
    Raglan O, Kalliala I, Markozannes G, et al. Risk factors for endometrial cancer: An umbrella review of the literature. Intl Journal of Cancer. Published online February 20, 2019:1719-1730. doi:10.1002/ijc.31961
  8. 8.
    Ghanbari Andarieh maryam, Agajani Delavar M, Moslemi D, Esmaeilzadeh S. Risk Factors for Endometrial Cancer: Results from a Hospital-Based Case-Control Study. APJCP. Published online October 2016. doi:10.22034/APJCP.2016.17.10.4791
  9. 9.
    MacKintosh ML, Crosbie EJ. Prevention Strategies in Endometrial Carcinoma. Curr Oncol Rep. Published online November 13, 2018. doi:10.1007/s11912-018-0747-1
  10. 10.
    Jordan SJ, Na R, Johnatty SE, et al. Breastfeeding and Endometrial Cancer Risk. Obstetrics & Gynecology. Published online June 2017:1059-1067. doi:10.1097/aog.0000000000002057
  11. 11.
    Satei J, Afrakhteh AN, Aldecoa KAT. Endometrial Adenocarcinoma in Young Women: A Case Report and Review of Literature. Cureus. Published online September 15, 2023. doi:10.7759/cureus.45287
  12. 12.
    Liu X, Jin S, Zi D. Overall survival prediction models for gynecological endometrioid adenocarcinoma with squamous differentiation (GE-ASqD) using machine-learning algorithms. Sci Rep. Published online May 24, 2023. doi:10.1038/s41598-023-33748-1
  13. 13.
    Pappa C, Le Thanh V, Smyth SL, et al. Mixed Endometrial Epithelial Carcinoma: Epidemiology, Treatment and Survival Rates—A 10-Year Retrospective Cohort Study from a Single Institution. JCM. Published online October 5, 2023:6373. doi:10.3390/jcm12196373
  14. 14.
    Foerster R, Kluck R, Rief H, Rieken S, Debus J, Lindel K. Survival of women with clear cell and papillary serous endometrial cancer after adjuvant radiotherapy. Radiat Oncol. Published online June 18, 2014. doi:10.1186/1748-717x-9-141
  15. 15.
    Abdulfatah E, Sakr S, Thomas S, et al. Clear Cell Carcinoma of the Endometrium. International Journal of Gynecological Cancer. Published online October 2017:1714-1721. doi:10.1097/igc.0000000000001050
  16. 16.
    Ferriss JS, Erickson BK, Shih IM, Fader AN. Uterine serous carcinoma: key advances and novel treatment approaches. Int J Gynecol Cancer. Published online July 1, 2021:1165-1174. doi:10.1136/ijgc-2021-002753
  17. 17.
    Yap S, Vassallo A, Goldsbury D, et al. Pathways to diagnosis of endometrial and ovarian cancer in the 45 and Up Study cohort. Cancer Causes Control. Published online October 9, 2022:47-58. doi:10.1007/s10552-022-01634-2
  18. 18.
    Shen Y, Yang W, Liu J, Zhang Y. Minimally invasive approaches for the early detection of endometrial cancer. Mol Cancer. Published online March 17, 2023. doi:10.1186/s12943-023-01757-3
  19. 19.
    Kuhn TM, Dhanani S, Ahmad S. An Overview of Endometrial Cancer with Novel Therapeutic Strategies. Current Oncology. Published online August 27, 2023:7904-7919. doi:10.3390/curroncol30090574


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