A major study carried out by Cancer Research UK scientists could revolutionise the way women with breast cancer will be diagnosed and treated in the future, by reclassifying the disease into 10 completely new categories based on the genetic fingerprint of a tumour.
Doctors should one day be able to predict survival more accurately in women with breast cancer based on these new subtypes, and better tailor treatment to the individual patient.
The research – published in Nature1 today (Wednesday) – is the largest global gene study of breast cancer tissue ever performed – the culmination of decades of research into the disease.
The team at Cancer Research UK’s Cambridge Research Institute, in collaboration with the BC Cancer Agency Vancouver Canada, analysed the DNA and RNA2 of 2,000 tumour samples taken from women diagnosed with breast cancer between five and 10 years ago.
- Classified breast cancer into at least 10 subtypes3 grouped by common genetic features that correlate with survival. This new classification could change the way drugs are tailored to treat women with breast cancer.
- Discovered several completely new breast cancer genes that drive the disease. They are all potential targets for the development of new types of drugs. This information will be available to scientists worldwide to boost drug discovery and development.
- Revealed the relationship between these genes and known cell signalling pathways – networks that control cell growth and division. This could pinpoint how these gene faults cause cancer, by disrupting important cell processes.
Study co-lead author, Professor Carlos Caldas, senior group leader at Cancer Research UK’s Cambridge Research Institute and the Department of Oncology, University of Cambridge, said: “Our results will pave the way for doctors in the future 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.
“This research won’t affect women diagnosed with breast cancer today. But in the future, breast cancer patients will receive treatment targeted to the genetic fingerprint of their tumour.
“We’ve drilled down into the fundamental detail of the biological causes of breast cancer in a comprehensive genetic study. Based on our results we’ve reclassified breast cancer into 10 types – making breast cancer an umbrella term for an even greater number of diseases.
“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.
“The next stage is to discover how tumours in each subgroup behave – for example do they grow or spread quickly? And we need to carry out more research in the laboratory and in patients to confirm the most effective treatment plan for each of the 10 types of breast cancer.”
Professor Samuel Aparicio, co-lead author of the study based at the BC Cancer Agency in Vancouver, Canada, said: “Breast cancer is a global problem and it’s exciting to see a new framework for the understanding of breast cancer emerge from our partnership with colleagues in the UK.
“The new molecular map of breast cancer points us to new drug targets for treating breast cancer and also defines the groups of patients who would benefit most.”
He added: “The size of this study is unprecedented and provides insights into the disease such as the role of immune response, which will stimulate other avenues of research.”
Dr Harpal Kumar, chief executive of Cancer Research UK, said: “This landmark study will completely change the way we look at breast cancer. It’s the result of decades of research by our scientists to identify the causes and drivers of the disease, which included a pivotal role in decoding the well-known BRCA genes.
“We’re entirely funded by the generosity of the public and this incredible support has put us at the heart of progress that’s underpinned the dramatic increase in the number of women surviving from breast cancer in the UK. This new study will enable us to make a further step-change for patients with breast cancer.
“Our research has underpinned important drugs, such as tamoxifen and herceptin, which have saved the lives of many thousands of women with breast cancer. And we’ve helped to improve and refine radiotherapy for breast cancer – a vital part of treatment for this disease.
“These latest results demonstrate again how solid scientific research is the foundation for translation into patient benefit and ultimately improving breast cancer survival.”
Cancer Research UK is a major funder of breast cancer research in the UK. Eight out of 10 women now survive breast cancer for more than five years, compared with five out of 10 women in the 1970s.
Dr Kumar added: “More women than ever before are surviving breast cancer thanks to our work. But there is much more to be done. We’ve a clear view of the questions- ahead and now we must focus on finding the answers.”
For media enquiries please contact the Cancer Research UK press office on 020 3469 8300 or, out-of-hours, the duty press officer on 07050 264 059.
1. The integrative genomic and transcriptomic architecture of 2000 breast tumours. Curtis et al. Nature. DOI: 10.1038/nature10983
2. To date the holy grail of molecular analysis of breast cancers has been to examine RNA – which translates DNA into proteins – to find out which genes are switched on or off in each tumour sample. By testing DNA from the same tumours the scientists were able to analyse genetic markers that vary from person to person – called single nucleotide variants (SNPs). They also examined the number of copies of each gene that is present on chromosomes in each tumour sample. This combined analysis of DNA and RNA helped reveal the identity of oncogenes – the drivers of cancer, and tumour suppressor genes – which protect against cancer. The analysis also revealed only a fraction of genes are switched on and off by these SNPs and copy number changes, paving the way for future studies to look for the remainder of the genetic faults that drive breast cancers. These studies will be guided by the map of the disease generated by the current study.
3. The research completely reclassifies breast cancer into 10 new categories based on gene activity rather than the currently used tests done in pathology laboratories, which look for the presence of markers such as oestrogen receptor (ER) or the cell surface receptor HER2.