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

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