The mutation of the BRCA1 gene that led Angelina Jolie to choose preventive mastectomies reduced her risk of developing breast cancer from 87 per cent to under five per cent.
A familial predisposition for breast or ovarian cancer may still exist involving some other gene or lifestyle
She is no doubt happy with this decision and delighted with the surgical procedures and reconstructions, having given a positive account of her experience so far.
She describes the series of life-changing major surgical procedures as relatively simple, with normal life resuming after only a few days. Her scars are minimal, the results “beautiful”, and her femininity remains intact.
What can we do here in Malta? Why are these tests so costly, especially in the US?
The reason why BRCA1 and BRCA2 defects tend to lead to cancers of the breast and ovary or prostate and testes is not known. Hundreds of different gene changes have been identified – some appear to be harmless variations.
On the other hand, high-risk gene defects can have disastrous effects. They fail to ensure our body’s DNA repair systems are free of faulty tissue and result in a significant increase in breast, ovarian and other cancers. The cancer risk varies significantly and depends on the location of the gene defect and other factors.
Genes do matter and more so BRCA genes, which affect what happens when cells divide. As molecular units of heredity, genes and their variants carry the instructions to build and maintain each cell in our body. We expect less than 0.2 per cent of women to carry this gene.
Women with harmful mutations in either BRCA1 or BRCA2 have risk of breast cancer that is about five times the normal risk, and a risk of ovarian cancer that is about 10 to 30 times the normal risk. Having a high-risk mutation does not always mean a cancer was actually caused by the mutation, rather than by some other factor like lifestyle.
Mutations from either parent may be passed on to both boys and girls. Each child has a 50 per cent chance of inheriting the mutated gene from the parent who carries the mutation. As a result, half the people with BRCA gene mutations are male.
BRCA mutations can increase the risk of other cancers, notably prostate, colon and pancreatic cancer. Methods to diagnose the likelihood of a patient with BRCA1 and BRCA2 mutations getting cancer were covered by patents owned by Myriad Genetics, and testing is expensive. This led to an ongoing landmark lawsuit in the US. A ruling is expected this summer. In Europe, this patent was revoked through a court order in 2004.
Counselling by experts is recommended. Genetic counsellors inform the person about the likelihood of a positive result, the risks and benefits of being tested, the practical meaning of the results, and the risk-reducing actions that may be taken if positive. Because the knowledge of a mutation can produce substantial anxiety, some people choose not to be tested or to postpone testing.
A gene defect may well interest your life insurance company – hence the reason why weighting against a familial breast cancer is outlawed in some countries. What happens in Malta is unclear.
Incidentally, those considering the radical surgical procedure or bilateral mastectomy and reconstructions undertaken by Jolie should get from their surgeon an upfront estimate of the risks involved. Ask for the good and bad results and the blunt truth about the cosmetic outcomes and complications.
Do not expect to read online the out-of-hospital treatment and expertise described in Jolie’s case. Much of what she underwent is simply not available as mainstream therapy. It is sound practice to have each client who requests such an irreversible operation reviewed at a multidisciplinary team meeting (geneticist, surgeon and counsellors).
It is considered poor practice for a surgeon to advise bilateral mastectomy without a psychological assessment or profile. Many women experience regret and a perceived ‘loss of self’ after the event, and this has led to some bitter lawsuits.
The test consists of DNA testing for mutations within the genes of interest. DNA is commonly extracted from a blood sample, although saliva can also be used. Once a mutation is identified, a search for this mutation can then be offered to other direct family members.
Testing is commonly covered by public healthcare programmes for people at high risk of having a mutation, not people with low risk. Maltese insurance companies remain reluctant to cover genetic tests for familial cancer.
The purpose of limiting testing to high-risk people is to ensure the person will receive a meaningful, actionable result from the test.
The tests can only be requested by a geneticist and are carefully interpreted before a patient explanation is given. In Malta, test results are commonly received within four to 12 weeks.
A negative test result may exclude a BRCA-related predisposition for cancer, although it will not guarantee that he or she will not develop a non-hereditary form of cancer. A familial predisposition for breast or ovarian cancer may still exist involving some other gene or lifestyle. Some 30 to 40 per cent of women seen at hospital clinics have this familial tendency without any identifiable gene defect.
Since taking birth control pills before the age of 20 is occasionally associated with very early development of breast cancer in BRCA mutation carriers, it has been suggested that teenage girls with a familial trait be tested.
Testing young children is not recommended.
Dr Psaila is lead EU ImagenX project consultant, Ministry for Health, National Health Screening Programmes.