Comments on Angelina Jolie's story
The recent news headlines that the award-winning actress, Angelina Jolie, had preventative double mastectomy because she was found to be a carrier of a BRCA-1 gene has been received with great interest by the public around the globe.
The BRCA-1 and BRCA-2 genes, which were identified approximately two decades ago, remain the most important genes which pre-dispose individuals carrying them to breast and ovarian cancer. These genes normally carry out repairs to our cellular DNA, which is frequently damaged on a daily basis. When the genes are faulty, then the individual’s ability to repair the DNA damage is impaired, thus leading to an increased risk of breast and ovarian cancer. Faulty BRCA1 or BRCA2 genes affect 1 in 300 individuals. The incidence is significantly higher in certain ethnic groups such as Ashkenazi Jews where the abnormal gene affects 2.5% of women.
The life-time risk of developing breast cancer is approximately 75% and that of ovarian cancer is approximately 40%. However, the risk depends upon the type of gene, whether it is BRCA-1 or BRCA-2, the site of the fault and other risk factors such as the use of the pill. Women with a very strong family history of breast or ovarian cancer, particularly if these cancers appear at a young age and in first degree relatives, should consider the possibility of genetic testing. They can visit their family doctor and request a referral to the local family history clinic. The gene test itself is straight forward and can be carried out on either a blood or saliva sample. It is always preferable that the test is carried out on a first degree relative, who was affected by the disease in order to identify whether a recognisable faulty gene is responsible. When considering the test, the patient should be offered counselling to discuss the implications of both a positive and a negative result.
Those who test positive for a BRCA-1 or BRCA-2 gene mutation would be offered several options, ranging from extensive surveillance (in the form of breast MRI, digital mammography and/or high resolution ultrasound scan) and prophylactic surgery. The timing of surgery will depend upon the woman’s personal circumstances, the type of gene involved and her age. Numerous studies have confirmed that prophylactic mastectomy would reduce the risk by 90%. This means for a woman, who has an 80% probability of developing breast cancer, prophylactic mastectomy would reduce the risk to 8%. The benefit of the surgery in prolonging lifespan depends upon the type of mutation and age at surgery. Recent advances in surgical techniques allow those women, who are considering prophylactic mastectomy, to achieve a good aesthetic result from a skin sparing mastectomy and immediate reconstruction, using implants or own-tissue to replace the breast volume. The recent introduction of biological mesh, derived from human or animal skin, now allows us to carry out bilateral skin sparing mastectomy and immediate reconstruction using implants as a single procedure with excellent aesthetic results.
I have been privileged to look after a large number of women of Ashkenazi Jewish origin in North London, where the prevalence of a gene mutation is relatively high (2.5%). The vast majority of women carrying the gene who opt to have preventative mastectomy seem to be highly satisfied with their decisions.
The risk of ovarian cancer remains significantly lower than that of breast cancer and this disease tends to develop at a later age. Unlike breast cancer, screening for ovarian cancer is relatively ineffective and, therefore, for those women who carry the mutation it would be reasonable for them to consider prophylactic removal of the ovaries and the tubes once they have completed their child-bearing. The additional advantage of preventative removal of the ovaries would also reduce the risk of breast cancer, particularly in women who harbour the BRCA-2 gene mutation. It should be born in mind that the BRCA-1 and BRCA-2 gene mutations increase the risk of other cancers such as pancreatic cancer and they also affect men. Men carrying the BRCA gene mutation have an increased risk of breast and prostate cancer. However, the life-time risk for breast cancer is relatively low compared with women (approximately 7.5%).
For women who carry a BRCA gene mutation, and who are specifically at increased risk of hormone sensitive (ER positive) breast cancer also have the options to consider taking anti-oestrogen drugs, such as Tamoxifen, to reduce the risk if they decide not to have prophylactic surgery. Recent advances in molecular biology have identified a very important enzyme, called PARP, which seems to present a very valid target for prevention of cancer among BRCA gene carriers. It is hoped that further advances in this field will lead to the discovery of simple drugs that down-grade the risk of cancer among BRCA gene carriers without resorting to prophylactic surgery in the future.
Finally life style modifications such as regular exercise, reducing alcohol intake and healthier diet (less animal fat and more fruits/vegetables) should be also considered to minimize the risk among carriers.