Unlocking the genetics of breast cancer

The news of Angelina Jolie's mastectomy last year brought breast cancer genetics, risk and prevention into the international spotlight. Her decision was only possible due to the efforts of researchers, over the past twenty years and more, to identify the inherited genetic mutations behind breast cancer and understand what this means for individual women and men.

Twenty years ago we didn't know why breast and ovarian cancer seemed to run in families, meaning there was no way of telling who in the family was likely to develop cancer in the future. This all changed starting with the BRCA1 and BRCA2 genes being cloned in the mid-1990s. Identifying a variety of mutations in these two genes has given us the knowledge that people with a BRCA gene mutation can have up to an 85 percent risk of developing breast cancer and up to a 50 percent risk of ovarian cancer.

However, BRCA mutations cannot explain all inherited risk of the disease. Continued research has led to the discovery of mutations in other genes that increase risk by varying amounts. These range from rare mutations in the genes TP53 and PTEN that increase breast cancer risk by a lot, to mutations in CHEK2, ATM, BRIP1 and PALB2 that are similarly rare but increase risk by a lesser extent. In total, known 'breast cancer genes' can explain 25-30 percent of breast cancer cases in which risk seems to have been inherited.

The knowledge and options now available to women is the true significance of scientific progress. Women with a family history can now have genetic testing to help assess their risk, regular screening to find cancers early, risk-reducing surgery, and risk-reduction with the drugs tamoxifen and raloxifene (chemoprevention). In the past twenty years having these options available has undoubtedly saved the lives of many women.

However, even with all the knowledge and options now available, there is still so much we don't know about the genes behind breast cancer risk. Although we know of some rare mutations that dramatically increase risk, there are likely to be many, many more genetic variations that are more common in the wider population but only increase risk very slightly on their own.

To add another layer of complexity, some mutations may only impact on risk when they are present in combination with others. It is only by identifying and fully understanding the combined effects of these common variations that we will be able to give much more accurate risk information to every individual.

In order to truly personalise our approach to screening and preventing breast cancer, a person's genetic information will also have to be combined with information on family history, biological factors such as breast density and lifestyle factors to give the most reliable picture of risk for every individual. It was therefore fantastic news last month to hear that researchers in the UK have made exciting progress towards precisely this goal.

These issues are some of those raised by Breast Cancer Campaign's 2013 gap analysis research and resulting action plan, Help us find the cures. In 2013, Breast Cancer Campaign brought together over 100 national and world leaders in breast cancer research to identify gaps in research that need to be addressed to accelerate progress in breast cancer. In the resulting paper the number one gap was: 'understanding how genetic changes lead to the development of breast cancer'.

Breast Cancer Campaign has invested over £11 million in research studying the genetics of breast cancer, and we've seen some brilliant achievements, but for us this is only the beginning.

Breast Cancer Campaign has committed to taking further action through research and campaigning that we believe will accelerate progress. Not only will we increase our research spending, we will focus on the most critical research questions, such as how genes influence the outlook for younger women and how genetics and epigenetics can help us to create predictive tests which will give precise and reliable information to even more women.

We have also called on bodies including Genomics England, NICE and international funders of research to use their positions to advance research in genetics and to ensure the implementation of clinical guidelines for familial breast cancer are monitored, so that we can ensure real change for women.

In only twenty years we have made huge progress in our knowledge of genetics and risk, and the options available for women. At Breast Cancer Campaign we take inspiration from the past twenty years and we're ambitious about the future. This is why we hope that by 2025 individual breast cancer risk will be more precisely predictable and up to 20 percent of breast cancers will be prevented. And, ultimately, by 2050 we believe that through global collaboration, we'll be able to overcome the disease.

The Progress Educational Trust is organising a free public event in central London entitled 'Risk Assessment: Breast Cancer, Prediction and Screening' on the evening of Thursday 8 May.

Book your place now by emailing sstarr@progress.org.uk