Cancer is the quintessential genetic disease, so it comes as little surprise to find it has benefited most from the unravelling of the human genome – the blueprint of life written in the digital DNA code of the cell's chromosomes. It is now more than 10 years since the full DNA sequence of the human genome was first published and the benefits of that understanding are now apparent in a remarkable breakthrough in breast cancer genetics.
For the first time, scientists have been able to tease apart differences in the DNA of breast cancer patients that go far beyond the results of classical medical science, based on the tradition of analysing tumour tissue under a microscope.
Researchers have used advances in genetics to determine 10 subtypes of breast cancer, each of which has a unique genetic fingerprint that could in the future determine a patient's tailor-made treatment – or cure.
At present, breast cancers are classified according to the presence or absence of a few "markers" or proteins found on the surface of tumour cells. In future, doctors will classify breast cancers based on the presence, absence or even activity of the smallest bits of DNA code.
The power of the latest study, published in the journal Nature, resides in the ability to retrospectively analyse some 2,000 frozen samples of breast-tumour tissue collected from women in Britain and Canada between five and 10 years ago.
Using powerful new developments in DNA analysis, such as computer-controlled "micro arrays" that can automatically scan the entire three-billion-letter code of the human genome for the smallest of mutations, scientists were able to confidently pigeonhole each tissue sample into one of 10 subtypes.
Each subtype had defined characteristics in terms of DNA variations and gene activity. The scientists could also show that each subtype displayed subtle but important features in terms of a patient's prognosis – in other words the DNA differences mattered.
Instead of looking at breast cancer as a single disease with a limited range of treatments, the scientists believe that their breakthrough demonstrates a range of cancer subtypes that can and should be treated differently.
"Our results will pave the way for doctors to diagnose the type of breast cancer a woman has, the types of drugs that will work, and those that won't, in a much more precise way than is currently possible," said Professor Carlos Caldas of Cambridge University, a senior member of the Anglo-Canadian research consortium. "Essentially we've moved from knowing what a breast tumour looks like under a microscope to pinpointing its molecular anatomy – and eventually we'll know which drugs it will respond to," Professor Caldas said.
It would mean that breast cancer patients in the future would have a genetic test before doctors decide on which treatment options to consider. This would end the blunderbuss approach of past therapy, leading to custom-designed "silver bullets" to treat cancer subtypes.
"This has the potential to change the face of breast cancer; from how we diagnose and treat it, to how we follow it up," said Julia Wilson, head of research at the charity Breakthrough Breast Cancer.
At present, some patients are receiving treatment that serves no benefit and is likely to have harmful side effects.
The DNA revolution could change this, although scientists emphasised it will take many years before NHS patients experience the benefits first-hand.
"I want to be very cautious here. This is a very important first step, and now what follows is to validate its clinical use," Professor Caldas said. "My caution is that this will not be available immediately to every single NHS hospital. It will be available to those hospitals with the clinical trials infrastructures and expertise."
Being able to classify breast cancers into 10 subtypes will have immediate implications for how clinical trials are designed. The streaming of a clinical trial's patients into different groups should lead to rapid development of new drugs and therapies tailor-made for each cancer.
"It's happening already in the context of clinical trials and I think a lot of these [genetic] tests, or a fraction of these tests, will be used on NHS patients within the next three to five years," Professor Caldas said. One of the first groups to benefit, he said, would be patients who are currently being "over treated" with potentially toxic drugs because current tests do not distinguish between those patients who will benefit from a particular drug and those who do not.
"We have a better classification with better powers to predict. It is a new way of selecting the best trials for patients and that's the first use we will make of this," Professor Caldas said.
"It's not going to change the way we manage women being treated in the NHS tomorrow, but it will surely change the way we manage clinical trials [so that] we will be running trials that are much more targeted at each of these different cancer subtypes," he said.
The study, carried out in co-operation with the University of British Columbia (UBC) in Vancouver, also discovered that certain genes are involved in either driving breast cancer or holding it back from spreading. Some of these genes are known to be involved in the production of enzymes within human cells, which will make them attractive targets for the development of new anti-cancer drugs, said Sam Aparicio of UBC, the study's co-leader.
Case study: 'I don't want my daughter to go through it'
Samantha Harper found a cancerous lump in her breast two weeks after giving birth to her son Freddie in 2009. Doctors thought the lump might be a blocked milk duct, but Samantha, from Northamptonshire, was sent for a biopsy when it got bigger.
"We weren't expecting the news. It was cancer, and it was aggressive," said Samantha, whose first child Sophie was 18 months old. "I was in shock. I was told I needed chemotherapy, and probably a mastectomy, because of the size. I was devastated because I was only 26 and my children were so young."
Scans revealed the cancer had spread to Samantha's lymph nodes. She began chemotherapy at Peterborough Hospital and the tumour shrank significantly. In July 2010, Samantha had her right breast removed and reconstructed at Addenbrooke's Hospital. She later tested positive for a mutation of the BRCA1 gene, which puts women at significantly higher risk of breast and ovarian cancers. She had her other breast and her ovaries removed as a preventative measure. She welcomes the new research as she hopes it could possibly help her daughter if it emerges she has inherited the mutation.
"The fact that I had the gene has made me anxious for my daughter's future. I don't want her to have to go through what I've been through. There is a 50 per cent chance that she could inherit it. That is why research is so important.
"Whenever I hear about developments in cancer research I instinctively think about Sophie".
Timeline: Milestones in the study of human genetics
1953 James Watson and Francis Crick at the Cavendish Laboratory in Cambridge and Maurice Wilkins of King's College London unravel the double-helix structure of the DNA molecule and so open the doors to the age of modern genetics.
1977 Fred Sanger of the Laboratory of Molecular Biology in Cambridge devises a method of "sequencing" the four-letter genetic code of DNA and thereby laying the foundations for unravelling the human genome.
1979 The first natural "tumour suppressor" – a gene named p53 – is discovered by Lionel Crawford and David Lane.
1990 The Human Genome Project is launched with the aim of sequencing the entire three billion letters on the DNA in each of the 23 pairs of human chromosomes.
1990 Mary-Claire King and her colleagues at UC Berkeley prove the existence of the first gene to be associated with hereditary breast cancer, now known as BRCA1.
1994 BRCA1 isolated by Myriad Genetics.
2003 Final version of the human genome is published. The ultimate "Book of Life" finds that we have about 23,000 genes, far less than originally estimated.
2006 Scientists find people can carry more than two copies of any gene. Variations in the "copy number" are normal and healthy.
2009 Stephen Quake of Stanford University declares he has decoded his own genome for under $50,000.