Breast cancer 'is 10 different diseases'

“Breast cancer is effectively ten different diseases,” the Daily Mail has today reported. The newspaper says that a “landmark” study has reclassified the country’s most common cancer in “breakthrough research” that could revolutionise the way we treat breast tumours.

During the study, researchers analysed the genetic features of 2,000 frozen samples of breast cancer tumours, taken from women diagnosed with the disease over the past 10 years. From this analysis, scientists found breast cancer could be classified into 10 different broad types according to their common genetic features. These different subgroups were associated with different outcomes for patients.

The large study has shown that breast cancer tumours can be classified into 10 new subtypes with varying outlooks. As such, this research is a valuable contribution to scientists’ understanding of the genetic basis of breast cancer and it may also help to explain why, at present, some tumours appear to respond well to treatment while others do not. It is possible that, in the future, doctors may be able to use this information to predict the outlook for individual breast cancer patients better and to tailor treatments accordingly. However it’s important to note that this study will not affect the way women are currently treated for breast cancer. As the scientists acknowledge, before these findings can affect clinical practice, further work is needed to understand how tumours classified under each subgroup behave, and also which treatments they may respond to.

Professor Carlos Caldas from Cancer Research UK has said that: “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”.

 

What is the news based on?

Today’s news is based on a laboratory study that analysed the genetic makeup and genetic activity in more than 2,000 breast cancer tumours. Understanding the genetic makeup of tumours is important as their genetics can potentially influence whether they are resistant or susceptible to particular drugs, and also their behaviour within the body. The aim of the study was to find out if the genetic characteristics of the tumours could be classified and matched according to clinical outcomes.

Personalised cancer treatment

One area at the forefront of cancer research is the move towards “personalised treatment”, in which doctors look at the unique genetics of a tumour and create a bespoke treatment plan designed to take advantage of a tumour’s vulnerabilities. For example, if a breast tumour carries a gene that might make it resistant to what is normally the first choice drug, doctors might instead opt for a drug the tumour has no genetic resistance to.

 

It’s not only in the area of breast cancer that scientists are exploring the issue. A whole range of cancers are being analysed in this way. In March this year, scientists released the results of a major study looking at cancer genes and how they govern responses to drugs. At present, the results are useful for research purposes rather than for treating patients, but they do represent a big step forward.

The research was generally covered as a “breakthrough” study by the newspapers, which took their lead from a press release accompanying publication of the study online. The Guardian’s headline – “Breast cancer treatment gets boost” – is misleading, as it will take several years before researchers will know whether and how treatments for breast cancer could be tailored to the new subtypes. In a similar vein, the Daily Mirror’s headline claiming there is “new hope” for breast cancer patients could falsely raise expectations in women who currently have the disease.

Also, the tone of some press coverage might be worrying for women currently living with the condition, as it suggests we currently struggle to treat breast cancer effectively. This is not necessarily the case as it is generally one of the cancers with the best outlooks. More than 80% of women diagnosed with breast cancer will still be alive five years later, and survival rates are continuing to improve. Of course, a lot more work is needed in the fight against breast cancer, but it is worth remembering that, in recent decades, there have been massive improvements in the treatment of breast cancer, and women given a diagnosis at the present time have a good chance of long-term survival.

 

Where did the story come from?

The study was carried out by researchers from the University of Cambridge, Cancer Research UK, the University of Columbia, Canada and a number of other institutions worldwide. It was funded by Cancer Research UK, the British Columbia Cancer Foundation and the Canadian Breast Cancer Foundation. The study was published in the peer-reviewed scientific journal Nature.

 

What did the research involve?

Scientists collected samples from more than 2,000 primary breast tumours that had been frozen and kept in tumour banks in the UK and Canada (primary means they originated in the breast tissue rather than spreading from another part of the body). They also collected information about the outcomes of the patients who had these tumours. They initially analysed the genetic characteristics of a set of 997 tumours (the “discovery group”). This was followed by analysis of a further set of 995 tumours (the “validation group”). These were used to check whether the first set of results could be reproduced. They also analysed 617 samples of normal (non-cancerous) breast tissue to compare with the tumour samples.

Scientists then looked at the variations in DNA in the tumours and related them to the activity of the genes in these tumours. They then looked at whether tumours could be classed into subgroups based on them sharing similar genetic variations and gene activity patterns, and whether these subgroups had different clinical outcomes.

 

What did the research find?

Using information from their “discovery” set of 997 breast tumours the researchers were able to classify the tumours into 10 different subtypes, based on similarities in their common genetic characteristics. The researchers found that the different subgroups had different clinical outcomes, including how likely women with different tumour types were to die from their breast cancer. Analysis of the second “validation” set of 995 tumours produced similar results.

As part of their extensive analyses, the researchers also identified several genes within the tumours that look like they may be involved in driving tumour growth. Many of these genes have not previously been thoroughly studied.

Overall, the researchers say that their findings show a new way to divide breast cancers into subgroups based on their genetic characteristics. In an accompanying press release, Professor Carlos Caldas from Cancer Research UK, who was one of the lead authors, 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 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.” Professor Caldas also argues that the variations in tumour genetics mean that we should now consider breast cancer to be an umbrella term for an even greater number of diseases.

 

Will the research change the way breast cancer is treated?

The new research provides a large, thorough look at the genetic behaviour of breast tumours and has identified subtypes of cancer that each have different long-term outlooks. This new knowledge provides a valuable contribution to scientists’ attempts to understand the genetic basis of breast cancer and why some treatments do and don’t work in different patients.

However, even though it provides a valuable contribution towards breast cancer research, the results of this study will not affect the way women are currently given routine treatment for breast cancer. This is because we have only really scratched the surface of how genetics might control subtypes of tumours within historical cancer samples. There is still a need to explore what various genetic combinations do within tumours in living people, including how they respond to therapies.

It is possible that, in the future, doctors may be able to use this information in routine clinical practice to set up personalised cancer treatments, where doctors could determine which genetic type of tumour a woman had and tailor treatment accordingly. However, more research is needed before this could become a reality. As the scientists acknowledge, further work is needed to understand how tumours classified under each subgroup behave and also how they respond to different treatments. As reported by the BBC, Cancer Research UK is going to begin using the new subgroups in its clinical trials of treatments for breast cancer.

Curtis C, Shah SP, Chin SF et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, Published online April 18 2012

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