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 tumour. Many of these genes could offer much-needed insight into breast cancer biology, allowing doctors to predict whether a tumour will respond to a particular treatment. Whether the tumour is likely to spread to other parts of the body or if it is likely to return following treatment.
The study, published online today 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.
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 tumour samples taken from women diagnosed with breast cancer between five and 10 years ago. The sheer number of tumours 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, today’s 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.
The research was generously supported by the BC Cancer Foundation, Canadian Breast Cancer Foundation – BC/Yukon Region and Prairies/NWT Region, Michael Smith Foundation and Cancer Research UK.
Dr. Sam Aparicio, Study Co-lead Author and Professor, Dept. of Pathology and Laboratory Medicine UBC; BC Cancer Agency Chair of Breast Cancer Research
“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. 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.
“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.
Professor Carlos Caldas, Study Co-lead Author and Senior Group Leader at Cancer Research UK’s Cambridge Research Institute and the Department of Oncology.
“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 means that women who are diagnosed and treated fairly uniformly today will in the future 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. Our results have 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 find how tumours classified under each sub group 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.”
Dr. Sohrab Shah, Study Co-Author and Scientist, BC Cancer Agency; Assistant Professor, Depts. of Pathology and Laboratory Medicine and Computer Science, UBC
“We have known for a long time that breast cancer is made up of different subtypes. Based on computational analysis of precise genomic measurements of 2,000 samples, our study provides a further subdivision of the breast cancer population into well-defined groups with different clinical behaviours.
“This provides a molecular scaffold upon which to develop tailored treatment strategies and identifies new cancer genes to target in future therapeutic development.”
Dr. Stephen Chia, MD, Medical Oncologist, BC Cancer Agency; Assistant Professor of Medicine, Department of Medicine, UBC
“The results of this landmark study by Dr. Aparicio and colleagues solidifies and now provides insight into the observation of the widely varied response to treatment and outcome in a population of breast cancers we see.”
Dr. Samuel Abraham, Vice President Research, BC Cancer Agency
“Real improvements to patient outcomes for cancer will only be achieved through research. If we have the will to lead through research and the translation of said research in the clinical arena we can provide a better future for all. Research underwrites our future.”
Ross MacGillivray, Vice-Dean, Faculty of Medicine University of BC
“This major discovery is the result of an international collaboration among fundamental, applied and clinical research scientists across disciplines. It’s this kind of interdisciplinary cooperation that puts BC scientists at the forefront of cancer research, and will no doubt lead to more breakthroughs in the near future.”
Douglas Nelson, President and CEO, BC Cancer Foundation
“This breakthrough is a momentous accomplishment, not only for the scientists and clinicians at the BC Cancer Agency, but also for the 105,000 British Columbians who join us as partners in discovery and supporting groundbreaking cancer research here in B.C. I’m thrilled to see such a tremendous advancement in the knowledge of breast cancer that will impact patient care globally.”
The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. For more information, visit www.bccancer.ca.
The BC Cancer Foundation is the bridge that connects philanthropic support and research breakthroughs in cancer knowledge. As the fundraising partner of the BC Cancer Agency and the largest charitable funder of cancer research in this province, we enable donors to make contributions to leading-edge research that has a direct impact on improvements to cancer care for patients in British Columbia. We fund with the goal of finding solutions. As an independent charitable organization, we raise funds exclusively for the BC Cancer Agency that support innovative cancer research and compassionate enhancements to patient care. Visit www.bccancerfoundation.com to make a donation or to learn how you can make a difference in the lives of those affected by cancer.
Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research. The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. This work is funded entirely by the public. Cancer Research UK has been at the heart of the progress that has already seen survival rates in the UK double in the last forty years. Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses. Together with its partners and supporters, Cancer Research UK’s vision is to beat cancer. For further information about Cancer Research UK’s work or to find out how to support the charity, please call 020 3469 6699 or visit www.cancerresearchuk.org
What did the scientists do?
They examined 2,000 tumours, but instead of studying them under a microscope, they analyzed their genetic profiles. The individual story of every tumour is written in its genes so although this approach is extremely labour intensive and requires highly sophisticated and expensive equipment, it provides scientists with exquisitely detailed information.
What were the researchers looking for?
They were searching for the genetic faults (mutations) that drive breast tumour development. Tumours are littered with faults, but only a select few drive its growth. So spotting “driver mutations” against a much larger backdrop of “passengers” (which do not affect tumour growth or survival) can be extremely difficult.
Why are driver mutations so important?
They are particularly interesting to scientists because cancer cells depend on them for their survival. Because they are cancer-specific, they are appealing targets for new treatments and diagnostics. They might also help doctors predict whether or not a tumour will respond to a particular course of treatment, or whether a tumour is likely to return after treatment.
What did they find?
The researchers identified several potential drivers. They also noticed that tumours clustered together into one of 10 groups; with each group having a distinct set of faults.
Have any drivers for breast cancer already been identified?
Yes. Some tumours have faults that make them produce large amounts of the oestrogen receptor (ER) so patients with these tumours may be offered tamoxifen or drugs called aromatase inhibitors. These block oestrogen activity, making it harder for the tumour to grow. Other tumours have a molecule called HER2 on their surface. Growth of these tumours depends on HER2 so these patients are often given Herceptin which stops HER2 from working.
How do we currently test for these faults?
Doctors look at samples of the tumour under a microscope. This gives them information about the part of the breast that it comes from. They will next examine the tumour to see whether molecules such as ER or HER2 are present or not. They classify the tumour according to what they see and this classification guides treatment decisions.
How could this approach be improved?
Women all over the world have benefited from drugs such as tamoxifen and Herceptin so this approach has saved many lives. But it also relies on the outward appearance of a tumour, which does not always provide meaningful information about its biology. The list of molecules that doctors test for is also too short to explain the complex nature of breast tumour behaviour. So doctors cannot always predict how a tumour will respond to treatment. An improved approach would paint a detailed molecular portrait of the tumour – this could help doctors plan treatment more effectively.
Why is this so exciting?
The research identified new cancer genes which could form the basis of next-generation treatments. This is particularly encouraging for research into tumour types such as the “triple-negative” breast tumours that have traditionally been very difficult to treat. These tumours do not have the molecules that drugs such as tamoxifen and Herceptin target so the choice of drugs that doctors can offer these patients is very limited. This work might lead to more treatment options for these patients.
Many of these genes could offer much needed insight into breast tumour biology; allowing doctors to predict whether a tumour will respond to a particular treatment, whether it is likely to spread to other parts of the body, or whether it is likely to return after treatment. This information could be used to help doctors pick the best treatment plan for individual patients.
Importantly, the researchers found that tumours within each sub-group had similar outcomes, suggesting that this work could form the basis of a classification system for breast tumours in the future. So, doctors will be better placed to offer treatments or clinical trials to patients most likely to benefit from them.
What is the next step?
Scientists will try to find out how specific faults promote tumour growth. They will look for those faults that could be targeted with new drugs in the future.
How will this work affect today’s breast cancer patients?
This research is unlikely to benefit women who currently have breast cancer. The equipment and expertise required to produce and analyze this amount of information is beyond the scope of today’s clinical laboratories, and we still don’t know which treatment plan is best for patients in each of these sub-groups. So the real power of this research is in its potential; it offers scientists and doctors a springboard from which new and exciting avenues of research and drug discovery can be explored.