Scientists identify key to preventing secondary cancers

  • 12,000 people die in the UK every year from breast cancer
  • The most common site for the disease to spread is the bone
  • Existing class of drugs for osteoporosis could stop the spread of the disease

Leading scientists from the University of Sheffield and University of Copenhagen have identified a possible key to preventing secondary cancers in breast cancer patients, after discovering an enzyme which enhances the spread of the disease.

Immunofluorescence image of multinucleate osteoclastSecondary (metastatic) breast cancer is the main cause of the 12,000 deaths which occur from breast cancer in the UK every year.

The most common site for the disease to spread is the bone – occurring in around 85 per cent of secondary breast cancer patients.

The new research found that the enzyme LysYl Oxidase (LOX) released from the primary tumour causes holes in bone and prepares the bone for the future arrival of cancer cells.

The findings suggest that identifying LOX in oestrogen receptor negative (ER negative) breast cancer patients early, could allow doctors to block the enzyme’s activity, preventing bone damage and the spread of tumour cells to the bone (metastasis), halting the progression of the disease.

The researchers also showed that treatment with bisphosphonate, an existing class of drug which prevents the loss of bone mass and is already used to treat diseases such as osteoporosis, was able to prevent the changes in the bone and the spread of the disease in mice.

The pioneering research, co-led by Dr Alison Gartland at the University of Sheffield’s Department of Human Metabolism, could lead to a better prognosis for cancer patients in the longer term.

Dr Gartland said: “This is important progress in the fight against breast cancer metastasis and these findings could lead to new treatments to stop secondary breast tumours growing in the bone, increasing the chances of survival for thousands of patients.

“We are really excited about our results that show breast cancer tumours send out signals to destroy the bone before cancer cells get there in order to prepare the bone for the cancer cells’ arrival.

Immunofluorescence image of a breast cancer tumour showing hypoxic cells in green and DNA in blue“The next step is to find out exactly how the tumour secreted LOX interacts with bone cells to be able to develop new drugs to stop the formation of the bone lesions and cancer metastasis. This could also have implications for how we treat other bone diseases too.”

Study co-leader Dr Janine Erler, formerly Team Leader in Cancer Biology at The Institute of Cancer Research, London, who now is Associate Professor at the Biotech Research & Innovation Centre (BRIC) at the University of Copenhagen, said: “Once cancer spreads to the bone it is very difficult to treat.

"Our research has shed light on the way breast cancer cells prime the bone so it is ready for their arrival. If we were able to block this process and translate our work to the clinic, we could stop breast cancer in its tracks thereby extending patients’ lives.”

The research, funded by Breast Cancer Campaign, Cancer Research UK, Novo nordisk foundation, Danish cancer society, lundbeck foundation, and both universities, is published today (27 May 2015) in the journal Nature.

Katherine Woods, Senior Research Communications Manager at Breast Cancer Campaign and Breakthrough Breast Cancer, said: “By unveiling the role that the protein LOX is playing, these results open up a whole new avenue for research and treatments that could stop breast cancer spreading to the bone. The research also adds weight to the growing body of evidence supporting the role of bisphosphonates in stopping secondary breast cancer in its tracks.

“The reality of living with secondary breast cancer in the bone is a stark one, which leaves many women with bone pain and fractures that need extensive surgery just when they need to be making the most of the time they have left with friends and family.”

She added: “Secondary breast cancer kills 1,000 women each and every month in the UK alone and yet we still don’t know enough about how and why breast cancer spreads to stop it.

“Our newly-formed charity is determined that by 2050, no one will lose their life to breast cancer and we’ll do this by ramping up our research efforts, in this area in particular, doing everything possible to achieve that goal.”

Additional information

The University of Sheffield
With almost 26,000 of the brightest students from around 120 countries, learning alongside over 1,200 of the best academics from across the globe, the University of Sheffield is one of the world’s leading universities.
A member of the UK’s prestigious Russell Group of leading research-led institutions, Sheffield offers world-class teaching and research excellence across a wide range of disciplines.
Unified by the power of discovery and understanding, staff and students at the university are committed to finding new ways to transform the world we live in.
In 2014 it was voted number one university in the UK for Student Satisfaction by Times Higher Education and in the last decade has won four Queen’s Anniversary Prizes in recognition of the outstanding contribution to the United Kingdom’s intellectual, economic, cultural and social life.
Sheffield has five Nobel Prize winners among former staff and students and its alumni go on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields.
Global research partners and clients include Boeing, Rolls-Royce, Unilever, AstraZeneca, Glaxo SmithKline, Siemens and Airbus, as well as many UK and overseas government agencies and charitable foundations.

The Institute of Cancer Research
The Institute of Cancer Research, London, is one of the world's most influential cancer research institutes. 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 cancer centres 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 leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
As a college of the University of London, the ICR 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 www.icr.ac.uk

Breast Cancer Campaign and Breakthrough Breast Cancer
Breast Cancer Campaign and Breakthrough Breast Cancer are joining forces in 2015 to become the UK’s largest breast cancer charity. United, they will achieve the shared ambition that by 2050 no one will die from breast cancer.
For more than 25 years Breakthrough Breast Cancer and Breast Cancer Campaign have funded cutting-edge research with an aim to preventing breast cancer, detecting it early, and treating it as effectively as possible. Together, we are determined to end breast cancer, once and for all.
They have a proud history of ground-breaking research:
The Breakthrough Generations Study – set up in 2004 – is world’s largest and most comprehensive study into the causes of breast cancer and is following more than 113,000 women throughout their lives.
The Breast Cancer Campaign Tissue Bank, the UK’s first ever national breast cancer tissue bank, is a unique collaboration with four leading research institutions to create a vital resource of breast cancer tissue for researchers across the UK and Ireland.
Breast cancer is not yesterday’s problem; it remains the most common cancer in the UK and accounts for nearly one in three of all cancers in women. In the UK, over 50,000 new cases of breast cancer are diagnosed each year – that's 138 a day.
For more information on Breakthrough Breast Cancer’s work to date, visit breakthrough.org.uk or follow us on Twitter or on Facebook
For more information on Breast Cancer Campaign’s work to date, visit breastcancercampaign.org or follow us on Twitter or on Facebook.

Contact

For further information please contact:

Amy Pullan
Media Relations Officer
University of Sheffield
0114 222 9859
a.l.pullan@sheffield.ac.uk