uterine cancer

see also:

• menorrhagia / PV bleeding
• cervical cancer
• neoplasia / cancer / tumours
• gynaecology

• overall risk for all women is 3%
• genetic:
  • FH increases risk
    • hereditary nonpolyposis colon cancer (HNPCC or Lynch syndrome) have 70% chance of endometrial cancer
      • most cases are caused by a defect in either the mismatch repair gene MLH1 or the gene MSH2
      • at least 5 other genes can cause HNPCC: MLH3, MSH6, TGBR2, PMS1, and PMS2.
  • mutations of the ARID1A and PIK3CA genes are frequently found together in the development of endometrial cancer, as well as in endometriosis-associated ovarian cancer
    • ARID1A is a tumor suppressor. When it mutates, chromatin, cellular material that keeps DNA compacted in cells, loses its structure, allowing cancer to spread.
    • PIK3CA is an instructional gene that tells the body to produce certain proteins and leads to uncontrolled growth of cells when it mutates.
    • these same mutations often are found in women who have endometriosis but many of those affected never develop endometrial cancer suggesting additional factors are required to develop cancer
• obesity
• advancing age
• oestrogen-related issues:
  • unopposed oestrogen therapy in menopause without progestogen (but taking combined increases risk of VTE and breast cancer)
  • anti-oestrogens in menopause can cause endometrial hyperplasia and increase risk to 1% per annum
  • combined oral contraceptive pill (OCP) reduces risk for 10 yrs after ceasing
  • higher number of menstrual cycles over a lifetime increases risk
    • early menarche before age 12yrs increases risk
    • late menopause increases risk
  • pregnancy reduces risk
    • 3 pregnancies reduces risk by 50% compared to no pregnancies ¹⁾
  • certain ovarian tumours such as granulosa cell tumor which secretes high levels of oestrogen
  • polycystic ovary syndrome (PCOS) 3-4x risk ²⁾
• iucd seems to lower risk
• diet - high fat diets are thought to be associated with increased risk
• lack of exercise
• type 2 diabetes appears to double risk but obesity and lack of exercise are confounding factors
• PH breast cancer or colorectal cancer (bowel cancer)
• endometrial hyperplasia
  • Simple atypical hyperplasia becomes cancer in 8% if untreated
  • Complex atypical hyperplasia (CAH) becomes cancer in 29% if untreated
• pelvic radiotherapy

• suspicious clinical pictures include:
  • any post-menopausal bleeding
  • clinically suggestive lesions such as cervical lesions, pelvic masses, enlarged uterus (although this may just be uterine fibroids (leiomyomas) or adenomyosis)
  • intermenstrual bleeding
  • post-coital bleeding
  • endometrial hyperplasia - eg. the perimenopausal patient with a preceding period of amenorrhoea, or those on oestrogen only Rx.
• indications for uterine sampling³⁾:
  • women over 45 years age
  • women with BMI > 30
  • women with FH bowel cancer
  • women with irregular bleeding
  • abnormal endometrium on US
  • NB. the chances of any endometrial pathology being present in a slim woman under age 45 years with regular menses is very small.
• indications of hysteroscopy⁴⁾:
  • suspected focal uterine pathology on US
  • suboptimal US visualisation of the endometrium
  • abnormal cavity seen on US
  • no endometrial sample can be obtained through pipelle biopsy

• short term vaginal oestrogen therapy < 2yrs appears to be safe for young endometrial cancer survivors⁵⁾