Targeting chemotherapy with genetic testing benefits women with aggressive breast cancer
Women with an aggressive form of breast cancer who have faults in their BRCA genes do much better on chemotherapy drug carboplatin than standard treatment, a major clinical trial reports.
Researchers found that women with advanced 'triple-negative' breast cancer who had inherited a BRCA mutation were twice as likely to benefit from carboplatin as docetaxel, which is currently standard of care for these patients.
The study was largely funded by both Breast Cancer Now and Cancer Research UK and led by a team at The Institute of Cancer Research, London, and King's College London.
The trial is set to change international clinical practice guidelines by ensuring that women with triple-negative breast cancer who are young or with a family history are considered for BRCA testing – so the best available treatment can be selected for them.
The study, published in the prestigious journal Nature Medicine today (Monday), was led by Professor Andrew Tutt in the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR) and the charity's Research Unit at King's College London, and Professor Judith Bliss in the Cancer Research UK-funded Clinical Trials and Statistics Unit at the ICR. It also involved hospitals around the UK.
Triple-negative breast cancer has limited treatment options because it doesn't respond to standard hormone therapies or targeted drugs like trastuzumab (Herceptin).
Advanced triple-negative breast cancer is usually treated with chemotherapy – but response rates remain low.
Researchers designed the trial to compare the effectiveness of docetaxel with carboplatin – a drug co-discovered at the ICR – as these two treatments affect cancer cells in different ways. Carboplatin creates a specific form of damage to a tumour's DNA, exploiting a weakness in some triple-negative breast cancers' DNA repair machinery.
When analysing the response in the 376 women with advanced triple-negative breast cancer across the trial, regardless of BRCA gene status, the researchers found that the two drugs worked similarly well.
But among the 43 women in the study who also had BRCA gene faults, those who received carboplatin were twice as likely to respond to therapy as those given docetaxel.
In these women, tumours shrank in 68 per cent of the patients treated with carboplatin, but only 33 per cent of the women on docetaxel.
Carboplatin also had fewer side-effects and delayed tumour progression for longer in women with BRCA gene faults – stalling tumour growth for around seven months, compared with four months for docetaxel.
The researchers believe carboplatin is more effective for this patient group because it works by damaging tumour DNA – and BRCA mutations impair the ability of cancer cells to repair the type of DNA damage created by this kind of 'platinum' drug.
Professor Andrew Tutt, Professor of Breast Oncology at The Institute of Cancer Research, London, said:
"Our study has found that women with triple-negative breast cancer who have BRCA1 or 2 mutations are twice as likely to respond to carboplatin as they are to standard treatment. It strongly suggests that many women with triple-negative breast cancer should be considered for testing for faults in the BRCA genes so those who test positive can benefit from carboplatin. Using this simple test enables us to guide treatment for women within this type of breast cancer. I am keen for these findings to be brought into the clinic as soon as possible.
"This is a great example of using personalised genetics to repurpose a chemotherapy drug into a targeted treatment, by understanding that its DNA-damaging effects might be particularly effective against cancer cells with deficiencies in DNA repair in appropriately selected patients."
Professor Judith Bliss, Director of the Clinical Trials and Statistics Unit at The Institute of Cancer Research, London, who led the management of the study, said:
"Women with triple-negative breast cancer often only survive for one to two years after the cancer has relapsed and spread to other parts of the body so there is an urgent need to find alternative treatments for this group of patients.
"Our study has shown that this doesn't have to mean developing new drugs. We can use existing – and often cheaper, generic – drugs more effectively by targeting treatment based on weaknesses in individual patients' tumours."
Professor Charles Swanton, Cancer Research UK's Chief Clinician, said:
"This exciting study brings us a step closer to delivering precise care to patients with breast cancer. Rather than offering all women the same standard of care, these results show that, for patients with inherited BRCA mutations, the drug carboplatin is not only a more effective treatment option, but also comes with fewer side-effects, sparing patients possible health problems, physical discomfort and emotional distress.
"The progress we've made treating breast cancer has been phenomenal, and now we're working to optimise treatments, so that we can give every patient the best chance of beating their cancer."
Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, which co-funded the trial, said:
"This is a landmark and long-awaited step forward for women with incurable and aggressive breast cancers who carry BRCA mutations – who until now have had no targeted options to rely on.
"While a cornerstone treatment, chemotherapy can be a blunt tool for many, with side-effects that can be difficult to cope with. It is fantastic news that carboplatin will now offer a more effective, kinder and targeted treatment to a group of patients who have long been in need of new hope. For those living with the impossible reality of incurable cancer, these precious extra months of better quality life before their condition worsens could mean absolutely everything.
"We hope future studies will now uncover whether this advance could benefit patients with early breast cancer too.
"We must now make sure this breakthrough reaches 'triple negative' patients that could benefit as quickly as possible. We urge NICE to include carboplatin in their guidelines on advanced breast cancer swiftly and NHS England to consider issuing commissioning advice to help ensure its routine adoption for these patients."
Neelam, who was a patient at The Royal Marsden when she took part in the TNT trial, said:
"I was diagnosed with metastatic triple negative breast cancer in early 2010 after finding a lump during a yoga class. I had treatment at The Royal Marsden, but sadly I found it had returned a year later, when I was diagnosed with lung metastasis. It was an incredibly difficult time for me; having cancer for the second time really shook me – especially the fact that it returned so quickly.
"I was determined to do anything I could to get treated, and luckily was able to take part in this trial. The support I had throughout from The Royal Marsden was second to none and with the regular check-ups that were required- it was like another 'tick' to say "I'm still here".
"Now, six years on, my scans show that I'm all clear of the disease. Its thanks to research like this, and The Royal Marsden who treated me, that I've been given a second chance of life."
Neelam, 57, started treatment under the TNT trial in October 2011 and finished in February 2012. She received carboplatin during the trial. She's remained disease free since finishing the trial.
For more information please contact Claire Hastings in the ICR press office on 020 7153 5380 or [email protected] For enquiries out of hours, please call 07595 963 613.
Notes to editors
Around 15 per cent of breast cancers are triple negative, affecting some 7,500 women in the UK each year.
The Institute of Cancer Research, London, is one of the world's most influential cancer research organisations.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden NHS Foundation Trust and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four centres for cancer research and treatment globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it is a world leader at identifying cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
A college of the University of London, the ICR is the UK's top-ranked academic institution for research quality, and provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk.
King's College London
King's College London is one of the top 25 universities in the world (2017/18 QS World University Rankings) and among the oldest in England. King's has more than 29,600 students (of whom nearly 11,700 are graduate students) from some 150 countries worldwide, and some 8,000 staff.
King's has an outstanding reputation for world-class teaching and cutting-edge research. In the 2014 Research Excellence Framework (REF), eighty-four per cent of research at King's was deemed 'world-leading' or 'internationally excellent' (3* and 4*).
Since our foundation, King's students and staff have dedicated themselves in the service of society. King's will continue to focus on world-leading education, research and service, and will have an increasingly proactive role to play in a more interconnected, complex world. Visit our website to find out more about Vision 2029, King's strategic vision for the next 12 years to 2029, which will be the 200th anniversary of the founding of the university.
World-changing ideas. Life-changing impact: https://spotlight.kcl.ac.uk/
About Cancer Research UK
- Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research.
- Cancer Research UK's pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
- Cancer Research UK receives no funding from the UK government for its life-saving research. Every step it makes towards beating cancer relies on vital donations from the public.
- Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years.
- Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK's ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 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 bring forward the day when all cancers are cured.
For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1022 or visit http://www.cancerresearchuk.org. Follow us on Twitter and Facebook.
About Breast Cancer Now:
- Breast Cancer Now is the UK's largest breast cancer charity.
- Breast Cancer Now's ambition is that by 2050 everyone who develops breast cancer will live – and live well. The charity is determined to stop women dying from the disease, working in a new, collaborative way and bringing together all those affected by the disease to fund research, share knowledge and find answers.
- Breast Cancer Now's world-class research is focused entirely on breast cancer. The charity supports more than 450 of the world's brightest researchers at more than 29 locations across the UK and Ireland. Together, they're working to discover how to prevent breast cancer, how to detect it earlier and how to treat it effectively at every stage so we can stop the disease taking lives.
- Breast cancer is still the most common cancer in the UK. Nearly 700,000 people living in the UK have experienced a diagnosis and one in eight women will face it in their lifetime. This year alone, more than 55,000 women and 350 men will be told they have the disease.
- The UK still has one of the lowest breast cancer survival rates in Western Europe and this year alone around 11,500 women will lose their lives. It's time to act.
- Breast Cancer Now launched in June 2015, created by the merger of leading research charities Breast Cancer Campaign and Breakthrough Breast Cancer.
- For more information on Breast Cancer Now's work, visit breastcancernow.org or follow us on Twitter or on Facebook.