Following Hollywood actress Angelina Jolie’s revelation last week that she’d undergone a double mastectomy to prevent breast cancer, it has emerged that a 53-year-old man had his prostate removed after abnormal cells were discovered during a study into early cancer detection.
We are becoming more aware about the role of genes that run in families and which increase the chances of getting cancer. BRCA1 and BRCA2 genes, discovered in the 1990s, can increase the risk of breast and ovarian cancer if a person carries a mutation in one of them - also called a gene alteration. In invasive ovarian cancer, for example, around 10% of women carry a BRCA gene.
Population-based studies have shown that around 5% of women with breast cancer under the age of 50 carry a gene alteration in their BRCA1 or BRCA2 gene that increases their cancer risk; this may be higher in certain groups.
BRCA gene alterations are more frequent in certain ethnic groups, such as people of Ashkenazi Jewish and Polish ancestry. These groups have “founder mutations”, thought to be inherited from a common ancestor. These are easier to find and test for. But in the majority of cases in the UK, genetic testing is more difficult as we need to look through the whole gene to find the fault.
Both men and women can carry BRCA gene alterations but the cancer risk is higher in women. The risk of breast cancer with BRCA1 and BRCA2 is around 50-80% over a lifetime and around 10-40% for ovarian cancer.
There is also a link to risk in prostate cancer and male breast cancer. Male cancers are more strongly associated with BRCA2 and the man who underwent surgery to have his prostate removed was found to be carrying BRCA2 - recently linked to more aggressive prostate cancer - and had family members who had suffered from breast and prostate cancers. Men are also offered the choice of BRCA gene testing on the NHS if there’s a family risk, or a BRCA gene mutation is found in other family members.
Who is offered BRCA1 and BRCA2 testing?
Generally in the UK testing is only offered to a person affected with a BRCA-related cancer if they have a family history. If a significant genetic alteration is found then testing can also be offered to people in their wider family.
In about 10% of cases a “variant of uncertain significance” or VUS is found in the gene. VUSs are often difficult to interpret as they may be associated with the risk of cancer but we don’t have enough information to be certain.
Although Jolie urged the price of testing in the US to be reduced from more than $3000, the cost to the NHS in the UK is around £600 for testing both genes.
The Wellcome Trust has just announced £2.7m to test breast and ovarian cancer patients for nearly 100 risk genes from 2014.
What if you’re a carrier?
Since 2006, the National Institute for Clinical Excellence has recommended offering annual MRI breast screening for all female BRCA gene carriers between the age of 30 and 50, and annual mammograms from 40 onwards.
Breast screening does not prevent cancer, so some women choose to have risk-reducing mastectomies along with reconstructive surgery, either using implants or tissue flaps, which is usually done at the same time as the mastectomies.
This service is available on the NHS to female BRCA gene carriers and can reduce breast cancer risk by 90-95%.
Several appointments are offered, including one with a clinical psychologist to discuss sexual and mental health issues, so that a woman can be certain surgery is the right choice for her. Around a third of female BRCA carriers in the UK are thought to choose to have breast surgery. It’s rare but sometimes an “occult” or hidden cancer is also discovered at the time of surgery.
Surgery can also be offered to prevent ovarian cancer by removing both ovaries and fallopian tubes - usually after a woman has had her family, so not before the age of 35. If this type of surgery is carried out before a woman is 45 it can also reduce her risk of getting breast cancer by a half. Up to 70% of female BRCA carriers opt for this kind of surgery.
Because BRCA2 is linked with more aggressive prostate cancer, it is likely that early prostate screening will be offered to these men so that removing the prostate can be carried out while the cancer is still at a very early stage. However, side effects can be serious, including infertility and possible permanent incontinence.
We still don’t know how far drugs can prevent cancer developing in BRCA gene carriers. Tamoxifen, for example, can help protect against breast cancers that respond to the female hormone oestrogen, but data on its use in BRCA carriers is limited. In BRCA1, the majority of cancers do not respond to oestrogen.
To complicate matters, the oral contraceptive pill protects against ovarian cancer but increases breast cancer risk.
Wider testing likely on the NHS
Testing for BRCA1 and BRCA2 is likely to become more widely available on the NHS. And more tests for other genes that could cause breast cancer may start to be offered too. Women who already have breast or ovarian cancer may not need a family history to be offered genetic testing.
As technology improves, we may offer testing more widely to unaffected women with a family history. We’ll also begin to understand more about the VUSs or uncertain variants in BRCA genes. In the case of television presenter Kirstie Allsop and her sister Sofie, for example, BRCA1 and BRCA2 weren’t found but their history suggested a genetic cause for the cancers in their family.
The outlook for women with BRCA genes will improve, with greater access to genetic testing and screening and risk reducing surgery for women who have not yet developed cancer.