Ovarian cancer is the most lethal gynaecological cancer but, thankfully, the incidence of the disease is low. The lifetime risk of the disease in the general population is only 1.4 per cent, but some women are at much greater risk. This is due to the fact that they carry a genetic mutation that makes them susceptible to developing the disease. The peak incidence in the general population is at 56 years of age.
Ovarian cancer can be difficult to detect in the early stages, as its symptoms are notoriously vague. The more common symptoms include abdominal bloating or distension, pain, or the finding of an abdominal mass. Less frequent symptoms include altered bowel habit, weight loss, decreased appetite and increased frequency of passing urine. Due to the fact that these symptoms can be vague and often attributed to other conditions, in 75 per cent of cases ovarian cancer is detected at an advanced stage.
Surgery alone can be curative in the early stages of the disease, but chemotherapy is required to treat more advanced presentations.
If the disease is found in the early stages, the five-year survival is very good: 90 per cent of women diagnosed with stage 1 disease survive at least five years. Unfortunately, for those presenting with advanced disease the prognosis is poor, with fewer than 25 per cent of women surviving five years after presenting with stage 3 to 4 disease.
Risk factors
A family history of ovarian cancer is a major risk factor and is present in 10-15 per cent of cases.
Other factors that increase the risk to a lesser extent include young age at onset of periods, late age at menopause, and never having had children.
Factors that have been associated with a decreased risk of developing ovarian cancer include having your fallopian tubes removed or tied, the use of the oral contraceptive pill, having had children, and breastfeeding.
Women with one family member affected by ovarian cancer have a 4-5 per cent risk, while those with two affected relatives have a 7 per cent risk of developing the disease. By contrast, women with hereditary ovarian cancer syndromes, who carry a harmful genetic mutation, defined as having at least two first-degree relatives (parents or siblings) with ovarian or breast cancer, have a lifetime risk as high as 13-46 per cent.
Genetic factors
The most common hereditary cancer syndrome associated with ovarian cancer involves mutations in the BRCA gene (breast cancer gene). People who carry harmful mutations in this tumour-suppressor gene are at increased risk of breast and ovarian cancer. The lifetime risk of ovarian cancer for carriers of BRCA1 is 35-46 per cent, and for BRCA2 mutation carriers it is 13-23 per cent. The risk of developing breast cancer by the age of 70 for carriers of BRCA 1 is more than 80 per cent, and for BRCA 2 carriers it is more than 45 per cent.
Other less common genetic syndromes found to be associated with ovarian cancer include Lynch syndrome and Peutz-Jegher’s syndrome. Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is associated with a 3-14 per cent lifetime risk of ovarian cancer. Women who have Lynch syndrome also harbour an 80 per cent risk of developing bowel cancer and a 20-60 per cent chance of developing cancer of the womb.
Peutz-Jegher’s syndrome – a rare condition causing abnormal skin lesions and bowel polyps, also known as hereditary intestinal polyposis syndrome – is associated with a 20 per cent lifetime risk of ovarian cancer. This condition is also associated with a 57 per cent risk of bowel cancer and an 11 per cent risk of pancreatic cancer.
Genetic testing for all of these conditions is available and involves a blood test for women with a strong family history of relevant cancers. The syndromes mentioned above are all autosomal dominant conditions, which means that if you test positive for the defective gene, your children have a 50 per cent chance of being affected by the abnormal gene.
Risk reduction with screening
Some women who have been found to be at high risk of ovarian cancer choose to undergo six-monthly screening by ultrasound and a blood test to look for abnormal elevations in an ovarian tumour marker called CA125. While this may detect some tumours, unfortunately screening has not been found to reduce death from ovarian cancer.
Cancers can develop between screening intervals and can be advanced by the time of diagnosis. CA125 levels are increased only in 50-60 per cent of early-stage ovarian tumours and, therefore, screening can miss some early-stage tumours. Screening is recommended only for women who decline risk-reducing surgery in the absence of a better alternative.
For high-risk women who decline risk-reducing surgery, some expert groups have recommended screening with transvaginal ultrasound and CA125 levels every six months. This should commence at the age of 35 years, or five to 10 years earlier than the earliest age of first diagnosis of ovarian cancer in the family.
While this may be a reasonable option, the evidence indicates limited effectiveness of screening in this population, and clinicians and patients should not be falsely reassured by negative screening results. Most groups advise risk-reducing surgery for this group by the age of 35-40, or when childbearing is complete.
Risk reduction with medication
It has been suggested that women with a hereditary ovarian cancer syndrome who have not elected for risk-reducing surgery and who are not trying to conceive should consider using the combined oral contraceptive pill, which has been found to reduce the ovarian cancer risk in BRCA carriers.
Risk reduction with surgery
Surgery to reduce the risk of ovarian cancer involves the removal of the ovaries and the fallopian tubes
and can usually be performed by laparoscopy or keyhole surgery.
The lack of effective screening has led many clinicians to recommend risk-reduction surgery when women no longer wish to conceive. The risk of developing a cancer in the area around the ovary after removing both ovaries and tubes is below 1 per cent.
Removing the ovaries and tubes of these high-risk women also decreases their risk of breast cancer by between 30 per cent and 75 per cent. Of course, prophylactic or risk-reduction mastectomy is recommended for women who carry the BRCA gene due to the very high risk of breast cancer; this reduces the risk of breast cancer to less than 2 per cent.
Woman who have a family history of ovarian cancer but who have not been found to carry an abnormal gene can consider risk-reduction surgery based on their own individual risk factors and concerns.
There are studies that suggest some ovarian cancers may start in the fallopian tubes. This has led to many gynaecologists suggesting the removal of fallopian tubes prophylactically in premenopausal women who are not at increased risk of ovarian cancer if they are undergoing hysterectomy and keeping their ovaries. Also, low-risk women who choose to have sterilisation procedures such as tying or clipping their fallopian tubes may wish to have their tubes removed instead, due to a potential decrease in their risk of developing ovarian cancer.
Most BRCA1 carriers will not develop ovarian cancer until they are over the age of 40, and the average age of diagnosis in this group is 50. Therefore, it is appropriate to consider risk-reducing surgery for BRCA1 carriers after the age of 35, once childbearing is complete.
By comparison, BRCA2 carriers who develop ovarian cancer usually do so a decade later than those with BRCA1; 2 per cent of BRCA2 carriers develop the disease by the age of 50, and the average age at diagnosis is 60. Therefore, BRCA2 carriers may wish to delay surgery until the age of 45 but by doing this would not benefit as much from the reduction in breast cancer afforded by the removal of their ovaries by the age of 35.
Women who are considering risk-reduction surgery but who want to have children should be counselled about alternative reproductive options including preservation of ovarian tissue (under investigation), surrogacy, and embryo cryopreservation (storage).
Hysterectomy may be performed at the same time as removing the ovaries and tubes, when there are other gynaecological reasons. This can often be completed laparoscopically. Women who have Lynch syndrome along with a high risk of cancer of the womb should be offered hysterectomy.
There are other situations in which some women might want to consider hysterectomy. These include some BRCA carriers with a history of breast cancer who wish to take tamoxifen for the treatment of breast cancer.
Tamoxifen increases the risk of cancer of the womb and, therefore, BRCA carriers with a history of breast cancer who are taking Tamoxifen would be advised to undergo hysterectomy at the same time as removing the ovaries and tubes if opting for risk-reduction surgery.
Hormone replacement therapy (HRT) is recommended for women who carry the BRCA gene after risk-reducing surgery until the age of 50, and this has not been found to increase their breast cancer risk.
Women who wish to take unopposed oestrogen HRT may consider having a hysterectomy as part of their risk-reduction surgery.
Combined HRT taken after the age of 50 is associated with an increased risk of breast cancer, whereas no such association has been noted with unopposed oestrogen HRT in this group. Unopposed oestrogen HRT can be used only by women who have had a hysterectomy.
Dr Eve Gaughan is an obstetrician-gynaecologist who works at the Rotunda Hospital in Dublin.
