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ASCO 2019: New blood test predicts breast cancer’s return at start of treatment

Video: Dr Ben O’Leary discusses a new blood test for women with advanced breast cancer which can predict
how well patients will respond to a new drug right at the start of treatment.

A new blood test for women with breast cancer can predict how well patients will respond to a new drug right at the start of treatment.

The new blood test detected genetic changes within women’s breast cancers which indicated that these patients were less likely to respond to treatment – and that their disease could be expected to come back quickly.

Targeted drugs have shown benefit for many women with advanced breast cancer, but some patients stop responding soon after starting treatment as their cancer evolves to become drug resistant.

In future, the new test could help identify nearly half of women with the most common form of breast cancer who are at the highest risk of early relapse – who will need further trials of new treatments to stop their cancer becoming resistant – as well as identifying those who will do very well on treatment.

Many scientists from The Institute of Cancer Research, London are attending the 2019 ASCO conference in Chicago. See all of our news, blog and video content from the event. 

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Early relapse

Scientists at The Institute of Cancer Research, London, analysed fragments of cancer DNA that have entered the bloodstream to study the effect of genetic changes in a woman’s tumour – often called liquid biopsies.

They took blood samples from 310 women with oestrogen receptor positive breast cancer – the most common form of the disease – who were taking part in a clinical trial of palbociclib and fulvestrant for advanced breast cancer.

The team found that 131 women – 42 per cent – had one or more of three changes in the tumour DNA circulating in the bloodstream that put them at risk of early relapse.

The research, presented today (Saturday) at the 2019 ASCO Annual Meeting in Chicago, was funded by the Medical Research CouncilBreast Cancer Now, and the manufacturer of palbociclib, Pfizer.

The p53 gene

Researchers at The Institute of Cancer Research (ICR) – a charity and research institute – and The Royal Marsden NHS Foundation Trust examined the impact of specific genetic changes within patients’ cancers at the start of treatment.

Women whose circulating tumour DNA contained changes in the well-known cancer gene, p53, saw their cancer come back after an average of 3.7 months, compared with 12.7 months in women without p53 gene changes.

An increase in the number of FGFR1 gene copies and a high level of tumour DNA in the bloodstream also shortened the average time before a woman’s cancer came back.

Women with these changes in circulating tumour DNA saw their cancer return after an average of 3.9 months compared with 12 months in women without these changes.

The study also found a link between faults in the p53 gene and the number and location of sites in the body to which cancer had spread.

Next, the blood test needs to be evaluated as part of different clinical trials to assess its value in other groups of patients, before it can start benefiting women with advanced breast cancer in the clinic.

The research follows a recent announcement by the ICR of a £15 million fundraising drive to complete a new £75 million Centre for Cancer Drug Discovery focusing on overcoming cancer evolution and drug resistance.

Predicting cancer’s next move

Professor Nicholas Turner, Professor of Molecular Oncology at The Institute of Cancer Research (ICR) and Consultant Medical Oncologist at The Royal Marsden, said:

“Exciting new targeted treatments like palbociclib are beginning to have a real impact on survival for women with breast cancer, but unfortunately many tumours which initially respond will later develop resistance and come back.

“Our study found that a new genetic test could detect right at the start of treatment those women whose cancers were most likely to develop resistance quickly to palbociclib. We could then adjust their treatment plan accordingly – trialling additional treatments from the outset to try and prevent resistance, or planning for a switch to another treatment as soon as resistance develops. We now need to assess in a clinical trial whether helping direct women’s care with this new test can offer improved survival and quality of life.”

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Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

“Cancer’s ability to evolve to become resistant to treatment is the greatest challenge we face in improving patients’ survival and quality of life.

“So-called liquid biopsy tests like this one are a key part of our toolkit in staying on top of cancers’ adaptability and evolution, and picking up the earliest signs of drug resistance. Detecting the potential of cancers to evolve resistance could allow us to predict cancer’s next move and to respond with adaptable new treatment plans.

“This study is a demonstration of the exciting new ‘Darwinian’ approach to treatment we will be taking once we have raised the money to complete our new £75 million Centre for Cancer Drug Discovery.”

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16 APR 2019 Targeted breast cancer drug – olaparib – given green light by EU

European Medicines Agency approves olaparib for women with BRCA-mutant breast cancer – 15 months after licensing in the US

The targeted cancer drug olaparib has been approved by the European Medicines Agency (EMA) for women and men with advanced breast cancer who have inherited BRCA gene mutations.

The decision comes 15 months after the drug was approved for breast cancer in the US by the Food and Drug Administration.

NICE has paused its appraisal of olaparib for NHS patients with breast cancer while waiting for manufacturer AstraZeneca to submit new data, and is not now planning to restart its review until around July.

The Institute of Cancer Research, London, discovered the genetic targeting of olaparib – which became the first cancer drug directed against an inherited genetic fault when licensed by the EMA for BRCA-mutation ovarian cancer in December 2014.

In a statement, the ICR welcomed the approval of olaparib for breast cancer as an important step towards making it available for NHS patients – but also criticised delays in making the drug available in Europe.

‘Extremely innovative treatment’

Professor Paul Workman, Chief Executive of the ICR, said:

“It’s fantastic news that olaparib has finally been given the green light by the EMA for people with BRCA-mutant breast cancer. But it’s also been enormously frustrating for patients across Europe to have had to wait so long to get the drug.

“Olaparib is an extremely innovative treatment which was the first cancer drug in the world to target inherited genetic faults. Yet it’s taking far too long for pioneering drugs like this to reach patients and we need to do more to fast-track the most exciting new treatments into the NHS.

“The EMA and NICE have started to be more nimble and flexible in their evaluation of evidence, but there is still more they could do and much that they could learn from best practice in the US and elsewhere.”

Researchers at The Breast Cancer Now Toby Robins Research Centre lead important study programmes to understand the genetic and environmental causes of breast cancer.

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‘Excellent news for patients’

Professor Andrew Tutt, who is Director of the Breast Cancer Now Research Centre at the ICR, was part of the early laboratory research at the ICR behind PARP inhibitors in patients with BRCA mutations, and led some of the early clinical trials of olaparib for BRCA-mutant breast cancer.

Responding to the decision, Professor Tutt said:

“Although the delays have been disappointing, I am delighted olaparib has now been licensed in Europe for advanced breast cancer in women who have inherited BRCA1 or BRCA2 mutations. It is excellent news for patients with this form of breast cancer.

“Olaparib is the first drug to be approved that is directed against an inherited genetic mutation. It is a perfect example of how understanding a patient’s genetics and the biology of their tumour can be used to target its weaknesses and personalise treatment.”

Emma Clarke, 46 from Cheshire, was diagnosed with primary breast cancer in 2016, and secondary breast cancer spread to her bones in 2018. Later genetic testing discovered she carried a BRCA1 mutation. She is currently being treated with chemotherapy and is due to begin radiotherapy soon. Her daughter recently discovered she also has the BRCA1 mutation.

Emma said:

“I have done a lot of research into my type of cancer – about having a BRCA1 mutation and the possible treatments available for me. Because I have the BRCA1 mutation, and that carboplatin is working well for me at the moment, I found out that olaparib has a good chance or working well for me and that it is already available in the US.

“I’m fortunate enough to be a private patient and have asked my doctor about starting olaparib, which I will begin taking as a maintenance treatment when my radiotherapy finishes in June.

“I whole heartedly support progress in targeted therapies and getting these to patients as soon as possible. Targeted therapies are at the forefront of treatments for patients, and give such hope at extending lives while living with fewer side effects than traditional chemotherapies.

“I was really surprised to see the length of the time gap between olaparib being available in the US and it being approved by the EMA. I hope for all the other BRCA+ breast cancer patients in this country that it is available on the NHS as soon as possible.

“With advanced-staged cancers like my own, once you have good evidence that a new targeted treatment is shown to work and extend lives, it should be available to patients.”

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Capturing cancer on the move – ICR photography competition showcases stunning images of tumour cells in action

Every year our researchers submit outstanding pictures to our Science and Medical Imaging Competition – telling a story about our pioneering work and its benefits for patients. Check out the fantastic images selected by our judges, and this year voted for by the public.

Each year, The Institute of Cancer Research runs a Science and Medical Imaging Competition – designed to cater for the moments in the lab or the clinic where science meets art.

The entries we receive for the competition have all been created in the course of our pioneering cancer research – but they are also exceedingly beautiful, and wonderfully effective at conveying broad messages about our work.

‘Divide and conquer’

The winner of this year’s competition – ‘Divide and conquer’ by ICR postdoc Dr Maxine Lam – is a great example. It shows a replicating cancer cell in vivid detail as it invades through blood vessels – and communicates something about the lethal process of cancer metastasis that words alone often struggle to convey.

Metastasis is one of the most challenging aspects of cancer, because it often makes the difference between life and death. Once cancer has spread to other parts of the body we have few effective treatments, and the disease is often fatal.

Scientists are therefore keenly interested in understanding how cancer cells spread so they can find ways of stopping it from happen.

And that has led to the development of ever more sophisticated and powerful imaging technologies so researchers can watch the process in action over time.

“I’m really excited and honoured to have won”

Dr Lam’s winning image was taken using a technology called confocal microscopy, and shows a cancer cell in pink invading through a layer of blood vessel cells, in yellow and cyan. The cancer cell has created a gap in the layer of blood vessel cells as it invades.

The picture illustrates a key step in metastasis called extravasation – where cancer cells move out of a blood vessel into tissue to spread to secondary tumour sites. Despite the importance of this step, very few models exist in the lab to directly visualise and understand it.

Dr Lam’s lab in the ICR’s Division of Cancer Biology uses a unique set-up to provide previously unseen detail into this process.

In the image white DNA inside the cancer cell has condensed into bright rods. This means that the cancer cell is in the process of dividing itself, even as it is invading – a remarkable yet terrifying sight. Dr Lam’s lab is using images like this to identify factors that could prevent cancer cells from being able to move and spread.

Dr Lam said: “I’m really excited and honoured to have won the ICR Science and Medical Imaging competition. This image captures two important moments in the life of a cancer cell, when it divides to make new copies of itself and when it leaves the circulation and invades new tissues, which is one of the most dangerous aspects of cancer.

“Seeing this process in action helps us to better understand how cancer spreads, and I hope this will help with developing new treatments.”

The public’s favourite

Dr Lam’s image was awarded the main prize in the competition by a panel of judges from the ICR and our partner hospital The Royal Marsden NHS Foundation Trust.

We also this year carried out our first ever public vote, asking our supporters on social media to choose their favourite from the judge’s shortlist.

There was lots of agreement between the judges and the public, but the vote picked a different winner – a stunning time-lapse image of a breast cancer cell on the move by PhD student Patricia Pascual Vargas.

Patricia Pascual Vargas’ photograph: Time-lapse image of a breast cancer cell on the move

Cancer cells can take on many shapes, squeezing through tissues and finding their way into places they shouldn’t be, using a complex network of adhesion molecules on their surfaces to move around.

Patricia’s image was taken using another type of technology called a total internal reflection fluorescence microscope (TIRF), and shows a very aggressive type of triple-negative breast cancer cell sensing its environment, by making contact through structures called focal adhesions.

This time-lapsed image uses different colours to show the position of focal adhesions over time. The yellow and red colours represent shorter adhesion times, and show that the cell is moving down and to the left.

Patricia and her colleagues are looking at how targeting certain genes affects the formation of adhesions, changing the cell’s shape and how it moves. It could be possible to prevent cancer cells from spreading around the body, making cancer easier to treat.

Patricia said: “I’m thrilled to have won the first ever public vote. My image helps to demonstrate that cancer cells aren’t static – they move and change shape, and this important characteristic helps them to adapt to their environment. By pinpointing how cancer cells do this we could prevent them from changing shape and stop them from spreading, which could save patients’ lives.”

Our fantastic shortlist

With another year of so many astounding entries, it’s important to recognise all of the fantastic images that made it onto our shortlist.

Dr David Mansfield

Cell death caused by radiotherapy – before and after, taken by Dr David Mansfield, Division of Radiotherapy and Imaging.

David Mansfield’s photograph: Cells within a tumour visualised before (left) and after (right) radiotherapy

This image shows cells within a tumour visualised before (left) and after (right) radiotherapy. Coloured immune cells move in to clear up the tumour cells in white, left behind after treatment. This helps the body gain vital anti-tumour immunity and long-term protection from recurrent disease.

Multiple members of the Clinical Studies Division

Detecting immune cell populations in a liver biopsy by Dr Mateus Crespo Dr Bora Gurel, Ana Ferreira, Rita Pereira, and Professor Johann de Bono, Division of Clinical Studies.

Photograph by multiple members of the Clinical Studies Division: Detecting immune cell populations in a liver biopsy

This multi-coloured image was taken using multiplex immunohistochemistry to light up a liver biopsy from a patient with metastatic cholangiocarcinoma, an aggressive cancer of the bile duct. Liver cells in yellow are being infiltrated by immune system T-cells in red and green.

Parames Thavasu

The exploding nuclei – using combination drug treatments to overcome DNA damage repair mechanisms in cancer cells, by Parames Thavasu, Division of Cancer Therapeutics.

Parames Thavasu’s photograph: cells of an aggressive form of breast cancer called triple-negative breast cancer

This image shows cells of an aggressive form of breast cancer called triple-negative breast cancer, which is difficult to treat and has poor outcomes. After treating with a drug combination that causes damage to DNA at different stages of cell division, ‘explosive’ damage to cancer cells has occurred.

Dr Rebecca Marlow

Proliferating cells in a tumour organoid of triple-negative breast cancer, by Dr Rebecca Marlow, Division of Breast Cancer Research.

Dr Rebecca Marlow’s photograph: Proliferating cells in a tumour organoid of triple-negative breast cancer

This image shows tumour organoids of triple-negative breast cancer, a hard-to-treat form of the disease, grown from tissue samples donated by patients.

The nuclei of cells are marked in blue, while the cytoskeleton that helps cells maintain their shape is green. Proliferating cells are pink, where cells in the organoid are growing and dividing.

Cutting-edge research

These eye-catching images illustrate just some of the cutting-edge research being carried out at the ICR, taken using sophisticated equipment purchased thanks to generous donations from our supporters.

From images like these our researchers are gaining unprecedented insights into the mechanisms that drive cancer, and new ways to target the disease to help treat patients.

Dr Chris Bakal, who leads the teams in which Maxine and Patricia work, and is a previous winner of the competition himself, said:

“It is a cancer’s ability to spread round the body which often makes it fatal. It is incredibly valuable to be able to image this process over time to give us the insights into cancer biology that we need to discover new treatments.

“Our winners have used cutting-edge imaging technology to create measurable, single-cell imaging in 3D environments, to provide a vivid picture of exactly how cancer cells metastasise.”

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Potential new treatment for advanced cancers

A potential treatment for therapy-resistant breast cancer patients has been uncovered by researchers at Cardiff University.

The European Cancer Stem Cell Research Institute, based with Cardiff University, has repurposed a current cancer therapy, TRAIL, to find a new treatment for advanced cancers that are resistant to anti-hormone therapy.

Up to 75% of women diagnosed with breast cancer will have a cancer driven by oestrogen signalling and almost all of these women will receive anti-hormone therapy, like Tamoxifen or Aromatase inhibitors, to treat their cancer. Unfortunately, up to 40% of patients receiving these hormone therapies will develop a resistance to them, leading to relapse with aggressive cancer.

Dr Luke Piggott, European Cancer Stem Cell Research Institute at Cardiff University, said: “Part of our research focus is to develop new therapies, with low levels of side effects, for breast cancers that are resistant to anti-hormone treatments.

“TRAIL has already been tested in multiple types of cancer, but hasn’t yet proved beneficial to patients. But we believe we have demonstrated that patients who develop resistance to treatment will benefit from TRAIL therapy, as we have identified specific changes in the cancer cells from these patients, which mean that their tumours become sensitive to TRAIL treatment.

“Additionally, we have shown in this patient group that TRAIL treatment targets a specific type of cell in a tumour called a cancer stem cell. Cancer stem cells differ to the other cancer cells, as they are the cells responsible for initiating tumour growth and spread, and have also been shown to be resistant to therapy.”

Dr Richard Clarkson’s team of researchers at the European Cancer Stem Cell Research Institute tested TRAIL on tumour samples collected from cancer patients who had developed resistance to anti-hormone therapy.

Their findings showed that TRAIL selectively killed cancer stem cells from these patients but that tumours that had not developed resistance to tamoxifen were unaffected by TRAIL.

Dr Richard Clarkson said: “Cancer stem cells are the cells responsible for relapse and for the spread of cancer, so by targeting these cells, along with the bulk of the tumour, we could transform the way we treat cancer, especially for those that are resistant to anti-hormone treatments.”

82 percent of the anti-hormone resistant tumour samples showed a significant response to TRAIL, whereas only 8 percent of tumour samples that had not previously seen anti-hormone therapy responded.

The experimental models showed tumour shrinkage after being treated with TRAIL and there was also a reduction in the number and size of tumours that have spread to other organs, a process known as metastasis.

Dr Clarkson added: “Although we have more research to do before this new drug gets into clinic, TRAIL represents a very promising therapy for a population of patients where there is currently very few options.”

Link to original article

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Our Recent Research News

We have recently provided funding to the Institute of Cancer Research (ICR) to help support their ground-breaking breast cancer research programme.

The ICR is one of the world’s most influential research organisations. They are the world leaders in identifying cancer genes, discovering cancer drugs and developing precision radiotherapy.

The ICR relies on support from charities, donors, partner organisations and the general public. It does not receive any government funding. That is why we chose the ICR as the first organisation to receive funding from us.

There are over 150 scientists and clinicians working at the ICR’s Division of Breast Cancer Research. The division focuses on identifying the genetic and environmental causes of breast cancer, so that they can improve diagnosis and treatment, and discover targets for cancer therapies.

Researchers at the ICR were responsible for one of the biggest discoveries in cancer genetics – the identification of the breast cancer gene BRCA2. This discovery has meant that people with a family history of breast cancer can be assessed for their future risk.

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Cell shape ‘maps’ could point to new cancer treatments

Scientists have created a ‘map’ linking the shape of breast cancer cells to the activation of their genes, which could point towards new treatments and help improve the effectiveness of immunotherapies.

In a revolutionary new approach, Cancer Research UK-funded scientists at The Institute of Cancer Research, London, used large sets of data to map out a network of links between cell shape and genes.

The researchers analysed cell shape in millions of images of more than 300,000 breast cancer cells, and data for more than 28,000 different genes.

Their study, published in Genome Research, found that changes in cell shape, which can be caused by physical pressures on the tumour, are then reflected in important changes in gene activity.

When they then used their maps to analyse thousands of samples taken from women who took part in the Cancer Research UK funded METABRIC study, the researchers discovered that these changes are linked to clinical outcomes for patients.

Hubs for information

They also identified key areas or ‘stations’ within the network that acted as hubs for the flow of information, controlling the levels of many other genes.

Specifically, they found that a protein called NF-kappaB plays a central role in this shape-gene network and could drive the growth and spread of cancer cells. This response was associated with tumour grade in patients and could be used to predict survival.

A map of the network of links between cell shape and genes

A map of the network of links between cell shape and genes (image: HebaSailem) 

These findings suggest that because NF-kappaB is rarely faulty in solid tumours, the surrounding mechanical forces are playing a large role in disease progression by switching the gene on. Because NF-kappaB is an important part of the immune response to cancer, this work also suggests immunotherapies might be improved by changing the mechanical forces in the tumour.

‘An exciting link’

Study leader Dr Chris Bakal, team leader in dynamic cell systems at the ICR, said: “Our study reveals an exciting link between the forces that act on cancer cells and the development of the disease.

“We used ‘big data’ approaches to carry out a complex analysis that would once have taken decades in a matter of months. The maps we’ve created of cell shapes and their effects on gene activity provide important pointers to new forms of cancer treatment, and ways of making existing immunotherapies more effective.”

Professor Karen Vousden, Cancer Research UK’s chief scientist, said: “Understanding the links between how a breast cancer looks and acts, alongside its genetic makeup, will help researchers develop a more detailed picture of the disease.

“The insights and approaches used in this research could one day lead to us being able to tell from appearance, how aggressive someone’s cancer is and how likely to spread, helping doctors decide the best course of treatment.”

 

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One thousand cancer patients have gene testing through efficient, affordable new process 16 NOV 2016

A thousand breast and ovarian cancer patients have now benefited from a faster BRCA gene testing process that was developed in the UK and is being adopted around the globe.

The 1,000th cancer patient has had ‘mainstream’ gene testing through an innovative process that offers affordable gene testing to cancer patients at their cancer clinic appointment.

The new approach was developed by researchers at The Institute of Cancer Research, London, through the Mainstreaming Cancer Genetics (MCG) programme, funded by Welcome.

Cancer patients could previously only access gene testing if referred to a genetics clinic. Referral criteria were complex and waiting lists for genetic appointments were long – many cancer patients did not get testing, even if they were eligible for it.

Patient-centred testing

The ICR and The Royal Marsden NHS Foundation Trust began an innovative pilot in 2013 to provide faster, more efficient and more patient-centred testing through routine cancer clinic appointments.

The pilot was quickly successful, and in 2014 mainstream gene testing of the BRCA1 and BRCA2 genes in eligible cancer patients became routine NHS care at The Royal Marsden.

In just the two years since, 1,000 cancer patients have had gene testing using the new process.

Professor Nazneen Rahman, Head of Cancer Genetics at the ICR and The Royal Marsden, said: “There were two main problems with the traditional system for gene testing. Firstly, gene itself testing was slow and expensive, and secondly the process for accessing gene testing was slow and complex.

“We used new DNA sequencing technology to make a fast, accurate, affordable cancer gene test, which is now used across the UK. We then simplified test eligibility and brought testing to patients in the cancer clinic, rather than making them have another appointment, often in another hospital.”

These two innovations have greatly increased the number of patients that can benefit from testing, without increasing costs.

Video courtesy of MCG Programme

Faster results

The Royal Marsden now offers tests to three times as many patients a year as it used to. The new pathway is also much faster, with test results received within four weeks compared with 20 weeks in the old system.

The gene test result helps patients to get the best management for their cancer.

Miss Fiona MacNeill, Consultant Surgeon at The Royal Marsden and President of the Association of Breast Surgery, said: “Having the BRCA test result is very helpful when discussing the surgical options with breast cancer patients. Some women with a BRCA mutation choose to have bilateral mastectomy because their risk of getting a new cancer in either breast is increased. It has been great to be able to quickly and directly arrange for testing at the cancer clinic.”

The results also provide information about whether hereditary causes of cancer are relevant for a patient’s family members. All women found to have a BRCA mutation have an appointment with the genetics team who coordinate providing information to relatives.

Many relatives choose to have a test to see if they have inherited the mutation. This allows them to make more informed choices and gives opportunities to reduce cancers in women found to be at high risk.

A cost-effective system

The patient response has been overwhelmingly positive with more than 95% of cancer patients wanting testing.

Professor Rahman added: “The main reason we wanted to change the system was because patients were telling us that they wanted to have better access to gene testing. We are delighted patients have found it so helpful and that it is more cost-effective for our cash-strapped NHS”.

“Many other centres across the country and internationally are adopting mainstream gene testing. This will help many women with cancer and will prevent cancers in their relatives.”

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