Scientists at the BC Cancer Agency and University of British Columbia have identified new breast cancer genes that could change the way the disease is diagnosed and form the basis of next-generation treatments.

Researchers have reclassified the disease into 10 completely new categories based on the genetic fingerprint of a tumor. Many of these genes could offer much-needed insight into breast cancer biology, allowing doctors to predict whether a tumor will respond to a particular treatment. Whether the tumor is likely to spread to other parts of the body or if it is likely to return following treatment.

"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.

"This is a major step forward in building the genetic encyclopedia of breast cancer and in the process we've learned there are many more subtypes of breast cancer than we imagined,” said Dr. Sam Aparicio, study co-lead author and professor in the Department of Pathology and Laboratory Medicine UBC; BC Cancer Agency Chair of Breast Cancer Research.

“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,” Aparicio added.

The study, published online in the international journal Nature, is the largest global study of breast cancer tissue ever performed and the culmination of decades of research into the disease.

In the future, this information could be used by doctors to better tailor treatment to the individual patient.

"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,” said Professor Carlos Caldas, study co-lead author and senior group leader at Cancer Research UK's Cambridge Research Institute and the Department of Oncology. "This means that women who are diagnosed and treated fairly uniformly today will in the future receive treatment targeted to the genetic fingerprint of their tumor.”

Caldas added, “We've drilled down into the fundamental detail of the biological causes of breast cancer in a comprehensive genetic study. Our results have reclassified breast cancer into 10 types – making breast cancer an umbrella term for an even greater number of diseases.”

He said the next stage is to find how tumors classified under each sub group behave. “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.”

The team at the BC Cancer Agency, in collaboration with Cancer Research UK's Cambridge Research Institute and Manitoba Institute of Cell Biology at University of Manitoba, analyzed the DNA and RNA of 2,000 tumor samples taken from women diagnosed with breast cancer between five and 10 years ago.

The sheer number of tumors mapped allowed researchers to spot new patterns in the data.

Study milestones include:

• Classified breast cancer into 10 subtypes grouped by common genetic features, which correlate with survival. This new classification could change the way drugs are tailored to treat women with breast cancer.
• Discovered several completely new genes that had never before been linked to breast cancer. These genes that drive the disease are all targets for new drugs that may be developed. This information will be available to scientists worldwide to boost drug discovery and development.
• Revealed the relationship between these genes and known cell signaling pathways – networks that control cell growth and division. This could pinpoint how these gene faults cause cancer, by disrupting important cell processes.

This is the second major breakthrough announced by BC Cancer Agency scientists in as many weeks.

On April 4, a team led by Dr. Sam Aparicio celebrated the decoding of the genetic makeup of the most-deadly of breast cancers, triple-negative breast cancer, which until then was defined by what it was missing, not what it was.

Similar to that announcement, the new discovery identifies genes that were previously unknown to be linked to breast cancer and makes it clear that breast cancer is an umbrella term for what really is a number of unique diseases.

While the research is unlikely to benefit women who currently have breast cancer, it substantially advances how scientists approach further research and clinical trials by providing them with a springboard to develop new treatment options and drugs targeted to specific genes.

The research was carried out in collaboration with the following institutes:

• British Columbia Cancer Agency, Vancouver
• University of British Columbia, Vancouver
• Department of Oncology, University of Cambridge
• Department of Applied Mathematics and Theoretical Physics, University of Cambridge
• Department of Genetics, The Institute for Cancer Research
• Oslo University Hospital
• Department of Histopathology, University of Nottingham
• Cambridge Breast Unit, Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre
• King's College London, Breakthrough Breast Cancer Research Unit
• Manitoba Institute of Cell Biology, University of Manitoba
• NIHR Comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London
• Institute for Clinical Medicine, Faculty of Medicine, University of Oslo
• Cambridge Experimental Cancer Medicine Centre.