30 years of BRCA

How the discovery of two breast cancer genes continues to drive progress

By Amy Warnock

A radiographer looking at a mammogram

A discovery was made 30 years ago. This discovery would change the way that we thought about the prevention and diagnosis of certain cancers, and even pave the way for a new type of innovative treatment.  

That discovery was identifying the first breast cancer gene, also known as BRCA1.  

We’re proud to have played an important role, from funding scientists involved in the initial discovery to supporting the development of drugs to treat cancers caused by a faulty BRCA gene.  

This is the story of BRCA, and how its discovery caused a domino effect of three decades of revolutionary research.  

Diagram of Chromosome 17
Diagram of chromosome 17 with a small area highlighted
A diagram of chromosome 17 showing the location of BRCA

Discovering BRCA1 

The idea of heritable cancer goes back a long way. As far back as 1866, French surgeon Pierre Paul Broca described the history of breast cancer in his wife's family, which included 10 women with breast cancer over three generations. 

Over 80 years later in 1948, British researcher Sir David Smithers published a paper that looked at the family trees of more than 450 people with breast cancer and showed that breast cancer can occasionally run in families.  

From here the evidence kept growing, and it became clear that these hereditary cases of breast cancer were being caused by a faulty gene. So, researchers began a race to find it. 

Although with today’s technology it’s possible to read an entire human genome in a matter of hours, back in the 1980s progress was painstakingly slow. Research groups from around the world were competing to be the first to discover the gene, which had been dubbed ‘Breast Cancer 1’ (BRCA1). 

By the early 1990s researchers were starting to narrow down the search for BRCA1 to a region in the middle of human chromosome 17.  

This was further narrowed down by a team of scientists funded by one of our predecessor charities, The Cancer Research Campaign, who published a paper that helped to pinpoint the search to an even smaller region on the chromosome. Importantly, they also confirmed that there were likely other breast cancer genes elsewhere in the genome (which we’ll come to later...) 

A team led by Professor Bruce Ponder (who went on to become the first director of the Cancer Research UK Cambridge Research Institute) then published a paper including a detailed map of the region on chromosome 17 that contained the gene. But it was a team of US scientists who, in October 1994, revealed the exact location of BRCA1. 

Read more about the discovery of BRCA1

A diagram of chromosome 13
A diagram of chromosome 13 with a small area highlighted
A diagram of chromosome 13 showing the location of BRCA2

The hunt for BRCA2 

But as we hinted at earlier, the discovery of BRCA1 isn’t the end of the story, as evidence from our scientists had suggested that there was at least one more important breast cancer gene still to be discovered.  

The hunt for BRCA2 was on.  

A team of our researchers led by Professor Mike Stratton at The Institute of Cancer Research were among the first to narrow down the search, by pinpointing a region on one end of chromosome 13.  

And, at the end of 1995, Stratton, along with a team that included several other Cancer Research Campaign-funded scientists, revealed the exact location of BRCA2. 

Read more about the discovery of BRCA2

What are the BRCA genes? 

Everyone has BRCA1 and BRCA2 genes. They’re an important type of gene called ‘tumour suppressor genes’ that stop the cells in our body from growing and dividing out of control. 

A fault (or mutation) in the BRCA1 or BRCA2 gene means that cells can grow out of control more easily. This can lead to cancer developing. 

Both men and women can have faulty BRCA1 or BRCA2 genes. People who inherit faulty versions of these genes have an increased risk of developing different types of cancers. This includes: 

  • breast cancer 
  • ovarian cancer
  • prostate cancer
  • pancreatic cancer (although the risk associated with prostate and pancreatic cancer is much lower)

Only around 1 in every 400 people have faulty BRCA1 or BRCA2 genes.  

Find out more about inherited cancers

The impact of BRCA 

We’ve come a long way in the 30 years since the first BRCA gene was discovered, and the impacts reach far beyond just the cancer type that gives the gene its name. 

Genetic testing for the faulty BRCA genes became available for clinical use in 1996, and in February of this year, the NHS launched a national BRCA gene testing programme for people with Jewish ancestry, as BRCA mutations are more common in this group.  

Since their discovery, Stratton estimates that thousands, if not millions, of people have been tested for faults in BRCA1 and BRCA2 genes. 

Knowing if they have a mutation in their BRCA genes can help people understand their risk of cancer and allow them to take steps to manage their health. This includes receiving early and more regular breast surveillance or taking preventative drugs like tamoxifen or anastrozole. Some people also choose to have their breasts or ovaries surgically removed to help reduce their cancer risk.  

Not everyone who is eligible will choose to have a genetic test, and there are important considerations to take into account for those who are thinking about getting a genetic test. 

As well as giving people more options around managing their risk, the discovery of BRCA genes also helped pave the way for a new type of treatment that is now used by thousands of people with faulty BRCA-driven cancers every year.  

Unleashing the potential of PARP inhibitors 

BRCA genes are linked to our DNA repair pathways. BRCA1 and BRCA2 instruct cells to make proteins that help repair damage to their DNA, a process that occurs constantly over a cell’s life.  

If a cell experiences damage to either BRCA gene, then its ability to repair its DNA is impaired. These cells are more likely to start growing out of control, increasing the chances of a cell becoming cancerous.  

But there’s a catch. As cells can only tolerate so much damage before they die, faults in the BRCA genes can also push them closer to the edge. 

This gave scientists an idea on how they could treat cancers involving a BRCA mutation. As cells with a BRCA mutation already have impaired repair systems, impairing it further might tip the cells over the edge, killing them.  

This is an idea that two research groups led by Professor Sir Steve Jackson at the University of Cambridge and Professor Ruth Plummer at the University of Newcastle were exploring. Their research had resulted in the development of two new drugs olaparib and rucaparib, known as PARP inhibitors.

These drugs target a protein called PARP, which is also involved in repairing DNA that has been damaged. So they wanted to test the theory that blocking DNA repair using PARP inhibitors in cancer cells with faulty BRCA genes would mean that the cancer cells would have no chance of surviving and die.  

But as this was a new concept, drug companies deemed it too risky to invest in. Instead, our predecessor, The Cancer Research Campaign, stepped up to support the two groups.  

And the theories were right. 

In 2005 our scientists published results showing that cancer cells bearing BRCA mutations were extremely vulnerable to PARP inhibitors. 

Read the full story of PARP inhibitors

PARP inhibitors were first used to treat ovarian cancers, with the National Institute for Health and Care Excellence (NICE) approving the use of olaparib to treat BRCA-mutated ovarian cancers in England in 2015.  

Since then, olaparib has also been approved for use in certain breast and prostate cancers.  

And more PARP inhibitors are being developed and approved for use every year. For example, at the beginning of this year, NICE recommended the PARP inhibitor talazoparib for treatment of advanced breast cancers caused by mutations to BRCA genes.  

But this research is still in its early days, so the full picture of how wide the impact of PARP inhibitors will be is still unknown.

There are ongoing trials to see if PARP inhibitors are effective in other types of BRCA-mutated cancers, including prostate cancer that has spread and pancreatic cancer. And beyond BRCA-mutated cancers, we’re also funding trials looking at the effectiveness of PARP inhibitors in other cancer types such as lung cancer, a type of brain tumour called glioblastoma, and urinary tract cancers.  

An illustration of a pill bottle with 'PARP inhibitors' written on the front

Continuing the journey 

So much progress has been made in the past 30 years, but in research terms, three decades is hardly any time at all. We’re still funding lots of exciting research projects and trials into the BRCA genes, so that we can continue to see improved outcomes for people with cancer.  

For example, Dr Sara Pensa and her team at the University of Cambridge have discovered that before becoming cancerous, breast cells with a BRCA1 mutation undergo changes similar to those normally seen during pregnancy. This research is still in its early stages, but they’re hoping to build on these findings and develop a blood test that could one day detect these early changes in people who have a faulty BRCA1 gene.  

And Professors Douglas Easton and Nitzan Rosenfield at the University of Cambridge are leading a programme to improve the early diagnosis of women who are at higher risk of both breast and ovarian cancer.  

Using pre-existing studies of women at high risk of these cancers, such as the EMBRACE study of women who carry mutations in their BRCA genes, the team will collect various patient samples. They’ll then study them using the most advanced genetic analysis technologies to find out whether these technologies are sensitive enough to detect breast and ovarian cancers from the samples.  

It is hoped that this could help to detect breast and ovarian cancers earlier in women who are at high risk, including those who have faulty BRCA genes.  

These are just a few of the many projects into BRCA genes that we’re funding right now. Since the discovery of the first BRCA gene 30 years ago, it’s clear that the impact of that discovery will continue to be felt for years to come.  

A nurse speaking to a woman at a mammogram appointment
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