PUBLISHED ON: 15 June 2015

The donor, having passed away only hours earlier, has made the decision to contribute to an ambitious new research project. She is one of the nearly 12,000 women who lose their lives to breast cancer each year in the UK.

The Breast Cancer Now LEGACY Study for Secondary Breast Cancer,  was set up to tackle one of the most important questions in breast cancer research by asking participants to agree to what’s known as a ‘rapid autopsy’ following their death. Tissue that is carefully collected during this autopsy is used to investigate how and why breast cancer spreads to other parts of the body. This process, known as metastasis, is the lethal part of breast cancer progression and results in the stage of the disease that is currently incurable – secondary breast cancer.

The problem

Breast cancer, like all cancers, is a disease in constant change. Like a turbulent ocean, the genetic and molecular characteristics of tumours are in continual motion, responding to the local environment and the conditions they need to survive in. Characteristics which appear in the primary tumour may disappear when it spreads elsewhere and new ones may emerge as a result of pressures to survive in the new environment.

These changes and adaptations, brought on by an orchestra of biological signals from the human body, are extremely difficult to replicate in the laboratory. Research in this area is limited by how much the experiments accurately reflect what is happening inside the body of a cancer patient.

LEGACY aims to change all that. By using tissue donated from patients who have died of secondary breast cancer, it will be possible to solve some of the pressing problems facing breast cancer research. For example, we don’t yet know exactly what biological cues cause cancer cells to spread to specific organs, or how they survive and grow there. This project will provide the basis for understanding the evolution of a patient’s breast cancer so that scientists can pinpoint the underlying biology of secondary breast cancer.

A lasting legacy

Although the first of its kind in the UK for breast cancer, other rapid autopsy programmes have been conducted, with success, in other cancer types.  The Gastrointestinal Cancer Rapid Medical Donation Programme (GICRMDP) was initiated in 2003 at John Hopkins University in the US and has to date completed more than 150 rapid autopsies. With a focus on pancreatic cancer (but also including colorectal cancer) this study aims to make ground-breaking changes for a cancer with one of the worst survival rates.

In 2005 the GICRMDP published some of its first results. Remarkably, the scientists had been able to collect over 500 separate samples of tissue and blood from just 20 donors, highlighting just how far and wide cancer can spread, but also the challenge we face in stopping it.  This comprehensive tissue collection allowed the scientists to identify a key gene involved in the spread of pancreatic cancer. The material collected by the GICRMDP also helped scientists from John Hopkins study the genetic evolution of pancreatic cancer within individual patients.

In 2010 they published research in the journal Nature which showed that cancer cells exist within the primary tumour that carry the genetic profile of those found in secondary tumours. By studying these mutations in detail, they calculated that it must have taken an average of at least five years for the primary pancreatic tumour to develop the mutations necessary to allow it to spread. By revealing this ‘window of opportunity’, the study opened up the possibility of finding ways to monitor patients for mutations that could eventually allow their primary cancer to spread, and even finding ways to stop this process.

John Hopkins University also set up a rapid autopsy programme for breast cancer research which managed to obtain tissue samples from multiple tumour sites from 15 different patients. Again, from just 15 patients, they were able to gather samples from over 180 separate secondary breast cancer sites. This material helped scientists to pinpoint various proteins implicated in the spread of breast cancer to different parts of the body.

It is this type of information that LEGACY hopes to acquire and seeing success in similar studies is a strong indicator that this project will make a real difference. What makes these studies really stand out is the fact that all this analysis can be done on samples collected from individual patients. This means that scientists can start to track the molecular and genetic journey a patient’s cancer has taken to reach other destinations in the body when it spreads. How the disease progressed in that period and how it was shaped by events on its journey could all be mapped out to reveal a wealth of information vital for the development of new ways to treat and prevent secondary breast cancer.

What does the future hold?

The LEGACY project is a pilot study. The scientists are aiming to carry out 12 autopsies and show that they are capable of removing, storing and analysing the various tissue samples. Beyond this, the scientists will look to continue recruitment and collect as many samples from different donors as possible. The more data we have, from as many donors as possible, the easier it will be to spot genetic or molecular patterns which can be used to advance our understanding secondary breast cancer. And from there, the future looks bright. Ground-breaking studies such as LEGACY have the power to transform our understanding of the disease and to help make Breast Cancer Now’s ambition a reality – that by 2050, everyone diagnosed with breast cancer will live.

Dr Matthew Lam is Breast Cancer Now's Senior Research Communications Officer

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