Difficult decisions faced by women with a BRCA gene mutation

The news about Angelina Jolie opting for a double mastectomy to reduce her risk of breast cancer has undoubtedly raised concerns among women with a family history of the disease. Whilst this news has certainly raised awareness of hereditary cancer, there are two key points that it is important to emphasize. Firstly, the majority of breast and ovarian cancer is not due to an inherited cause, and secondly, double mastectomy may not be the right choice for every woman who has a genetic predisposition to the disease.

One in eight women will develop breast cancer at some point in their lifetime, mostly after the age of 50. Ovarian cancer is less common, with approximately one woman in 70 developing the disease, again usually after the menopause. Many women will therefore have a family history of the disease and most of these women will not be at risk of hereditary cancer.

Most cancer occurs as we get older because our cells acquire faults (mutations) in their DNA over time. These mutations can affect genes that regulate cell growth. Most of these, so-called somatic mutations, are repaired by highly evolved biological mechanisms. The BRCA1 and BRCA2 genes encode proteins that play an essential role in DNA repair, and so help to prevent cancer developing. Although our cells acquire mutations through ageing, most of us also carry inherited mutations we were born with. These 'constitutional mutations' can affect how our bodies develop and function. Constitutional mutations in BRCA1 or BRCA2 can affect DNA repair and cause an increased risk of developing cancer. However, only around one in 500 people from most populations carry a mutation in either BRCA1 or BRCA2, making them a rare cause of breast cancer.

A person who inherits a BRCA1 or BRCA2 mutation will be more likely to develop breast and ovarian cancer. However, cancer is not inevitable. The lifetime risks associated with mutations in these genes are high (up to approximately 80 percent risk of breast cancer and 50 percent risk of ovarian cancer by age 70). However, the risk to the individual woman depends on a number of factors, such as age, ethnicity, family history and the gene involved. Men who have a BRCA1/2 mutation may also be at increased risk of cancer and, like women, can pass a mutation onto their children.

A woman with a strong family history of breast and ovarian cancer will be offered genetic counselling via a Regional Genetics Centre. Genetic counselling is provided by doctors and genetic counsellors with specialist training in clinical genetics and aims to help the individual and family to understand and adjust to the genetic condition and to choose a course of action to manage the risks.

In some families, genetic testing may be offered. For genetic testing to be useful in clarifying a person’s risk of developing cancer, a gene mutation must first be identified in a relative who has had the relevant cancer (a diagnostic test). If such a mutation is found, a predictive genetic test for that mutation can then be offered to other members of the family. Deciding whether or not to take a genetic test involves careful consideration of the possible outcomes and implications of testing for the individual and family.

For women who have inherited a BRCA1 or BRCA2 gene mutation there are complex and difficult decisions to make about how to manage the cancer risks. Breast screening is offered from age 30 and involves a combination of mammograms and MRI, magnetic resonance imaging scans, which are more sensitive than mammograms at detecting early cancer in young women. At present there is no ovarian screening available on the NHS, but women with a mutation may opt to have their ovaries and fallopian tubes removed once they have completed their families and when they reach their early 40s.

Double mastectomy and reconstruction is an option that women may consider. This surgery reduces the risk of breast cancer by 90 percent, bringing the risk down to a level similar to that of women in the general population. However, the psychological, social and physical impact of risk-reducing surgery needs careful thought. For some women, the decision to have surgery is straightforward; for others it is extremely complex. Involvement of the multidisciplinary team and the provision of support, both during decision-making and after surgery, are vital.

It is important to remember that most breast and ovarian cancer is not inherited. However, the revelation made by Angelina Jolie raises awareness of the difficult choices faced by women with a strong family history of the disease. It also highlights the importance of providing genetic counselling, information and support to women who are making tough decisions about genetic testing and risk management.