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Old 04-18-2012, 03:31 PM   #1
Lani
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Major study of 2000 tumors divides breast cancer into 10 diseases

Already read the article-- lumps both ER+ and ER- her2+ tumors into same category which has worst prognosis on their chart which was........generated before perception started to be given adjuvantly

It seems to me their will be additional subdivisions in the future, but article says they hope confirmatory work within 2-3 years may make this classification a working one for use clinically.


Contact: Brian Lin
brian.lin@ubc.ca
604-822-2234
University of British Columbia
Scientists rewrite rulebook on breast cancer in landmark global study

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.

Note to editors:

*Nature. "The integrative genomic and transcriptomic architecture of 2000 breast tumours." Curtis et al. DOI: 10.1038/nature10983
Quotes:

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

Media Contact
David Weir
Senior Public Affairs Officer
Provincial Health Services Authority

t. 604.675.4000 ext. 554292
c. 604.861.8079
David.Weir@phsa.ca
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Old 04-18-2012, 04:18 PM   #2
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Re: Major study of 2000 tumors divides breast cancer into 10 diseases

Lani,

Thanks for sharing the exciting news. One question: did you mean to say "...generated before 'Herceptin' started to be given adjuvantly"?
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Old 04-19-2012, 12:17 PM   #3
Lani
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Re: Major study of 2000 tumors divides breast cancer into 10 diseases

Absolutely. Herceptin aka "vitamin H" on this board, not perception!
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Old 04-19-2012, 07:40 PM   #4
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Re: Major study of 2000 tumors divides breast cancer into 10 diseases

Lani is there a link to the article? Can you explain the 10 types? How do thy lump hormone positive and her2 together? I have had some genetic assays done on my tumor and lymph spread so I am interested in how they broke it up into 10 groups and what the profiles were.
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Old 04-19-2012, 07:59 PM   #5
Lani
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Re: Major study of 2000 tumors divides breast cancer into 10 diseases

http://www.nature.com/nature/journal...ture10983.html

Not sure this will work, but try

Otherwise google entrez pub med and put in Aparicio S

Of the 10 subtypes, one is her2 + and includes both Er+her2+ and ER- her2+ Of all the 10 subtypes, when not treated with perception, it had the worst prognosis.
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Old 04-19-2012, 09:13 PM   #6
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Re: Major study of 2000 tumors divides breast cancer into 10 diseases

Does that mean Her2 is distinct front the other 10 types? I found the article too scientific for me to read! How does this fit with the new BRCA information?
Also other mutations such as P53 expression - how does this fit in? I'm sorry but I find this so confusing.
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40 year old Mum to three gorgeous kids - son 5 and daughters 8 and 11
Wife to my wonderfully supportive husband of 17 years!
22 February 2011 - Diagnosed Early Breast Cancer IDBC Stage2b (ER/PR -ve, Her2+ve +++) - 38 years old
(L) skin sparing mastectomy with tissue expander, axilla clearance (2/14 affected) clear margins.
Fec*3, Taxotere and herceptin*2 - stopped due to secondary diagnosis

June 24 2011 Stage IV - Skin met, axilla node, multiple lung lesions

Bolero3 trial - Navelbine, Hereptin weekly, daily Everolimus/Placebo
February 2012 - July 2012 Tykerb and Xeloda - skin mets resolved, Lungs initially dramatically reduced but growing again
August 2012 (turn 40!) tykerb and herceptin (denied compassionate use of TDM1) while holidaying in Italy!
September 2012 - January 2013 TDM1 as part of the Th3resa trial - lymph nodes resolved, lungs slowly progressing.
January 2013 - herceptin, carboplatin and Perjeta (compassionate access)
April 2013 - Some progression in lungs and lymph nodes - Abraxane, Herceptin and Perjeta
July 2013 - mixed response - dramatic reduction of most lung disease, progression of smaller lung nodules and cervical and hilar nodes - ? Add avastin.
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Old 04-20-2012, 12:34 AM   #7
Lani
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Re: Major study of 2000 tumors divides breast cancer into 10 diseases

the new BRCA info is entirely separate info--but may someday serve to separate her2+s (and triple negatives) into those that are more and less aggressive based on whether two genes are amplified/overexpressed or just one

the genes and pathways of 2000s tumors were examined and her2+ breast cancers whether ER+ or ER- had more in common with each other than they did with any other types of breast cancer and...if perception was not given adjuvantly...had the worse prognosis of all 10 types if I read the graph correctly

p53 is just another gene, in this case a tumor suppressor gene, which can be mutated in breast cancer. This study looked at genes and copy numbers as well as pathways (including immune gene pathways)

If you try to read scientific papers by substituting words like chocolate and ice cream for p53 or BRCA they are a lot easier to get through!!!
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Old 04-20-2012, 03:30 AM   #8
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Re: Major study of 2000 tumors divides breast cancer into 10 diseases

Thanks Lani for responding to Amanda's questions as I was also struggling to understand.
Just to clarify her 2 tumours regardless of their hormone receptor status are a distinct subset that before vit h had the worst prognosis? How does this fit in with thoughts that her 2 +and ER+ have a better prognosis than her2+ and ER- ? Have I just got this mixed up?
Thanks Ellie
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Old 04-20-2012, 07:55 AM   #9
Lani
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Re: Major study of 2000 tumors divides breast cancer into 10 diseases

NO, you don't. Most series just have tumors divided by their ER, PR and her2 by Immunohistochemistry staining (or by ER and PR by IHC and her2 by FISH)

Here they divided the tumors by their genetic components by analyzing their "genetic fingerprint"

ER by IHC can be inaccurate due to residual dye from Sentinel lymph node locating, ER and PR and her2 by IHC can be inaccurate because the sample was not placed in formalin and fixed until later (see a recent one of my posts)

Going back to the gene rather than testing for the protein (the final product of gene DNA to messenger RNA to constructed protein, which may be modified) is going back to the most exact identification of what makes the tumor the way it is by the most exact testing.

It is as if they sent out partially blind people to do the census and they came back with their best bet of the characteristics of the citizens they spoke with, rather than a swab from the
citizen's cheeks which would have proven who was male vs female, carbon 14 testing of their age (rather than their stated age-- many "fib a bit'), hair samples to test roots (similarly true hair color vs that which is perceived or reported)...

So it is not surprising that the results on prognosis are different when one is looking at apples and oranges vs smoothie components.

I am a bit doubtful that these 10 groups are the end of the story... but none can blame them from trying to find groups of patients who can be treated similarly as treating each tumor individually will be very expensive for society.
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Old 04-20-2012, 12:01 PM   #10
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Re: Major study of 2000 tumors divides breast cancer into 10 diseases

Thanks Lani for explaining. I strongly suspect that you are right and there will be many more groups identified as research continues. I often remind myself of my oncs comment that every bc tumour is individual as is every patients immune system and response! On one hand this seems a good thing but on the other seems to make the quest for a cure for all very elusive!
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Old 04-20-2012, 05:54 PM   #11
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Re: Major study of 2000 tumors divides breast cancer into 10 diseases

Thanks for this, Lani. I still struggle to explain to folks the type of breast cancer I was dx'd with. If it weren't for this site, and all the research I did on my dx, I would be in the dark, like so many others. And, I would probably not be here to write this!! Thanks to this website, and the amazing people who post here I was, and still am, able to get cutting edge information that even my doctor is not aware of. And because of this I was able to get Herceptin, prescribed "off label" for my early stage breast cancer, strongly Her2+, before it was approved for non-metastasized BC. WOW
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