We kicked off the symposium in a packed out lecture theatre at the Royal College of Physicians with a welcome from Prof Charles Coombes (Chair of the symposium organising committee) who gave a very powerful reminder of why we were all there by showing The Last One video.
Since we launched Breast Cancer Now with The Last One campaign, we’ve sadly lost Rashpal and Danielle, who featured in the video. We took a moment to remember them and everyone who has lost their life to breast cancer in the past year.
Signatures in the genes
To help us get to a world where no one dies of breast cancer, we need to be able to answer seemingly basic questions, like what goes wrong with DNA to make it instruct cells to grow out of control and become cancer?
Breast cancer is driven by DNA that has become faulty during our lifetime, these faults are known as driver mutations. Prof Sir Mike Stratton’s team have now documented 93 driver mutations - a finding we’ve previously covered in more depth.
So what can we do with this near complete catalogue of driver mutations? For a start we can develop drugs that target these mutated genes. But we can also understand a lot about the causes of breast cancer.
As Prof Stratton explained, genetic mutations leave a kind of “signature” in the DNA and his team is now trying to work backwards to see what has ‘written’ those signatures - work we’ve previously written about.
We returned to the topic of driver mutations later in the day with Prof Carlos Caldas, who has used information about driver mutations and other DNA errors to devise a new classification system for breast cancer.
His 10 types of breast cancer each have distinct profiles - both in terms of how the cancer behaves and outcomes for patients. This could help us to predict tumour progress more accurately and ensure that patients are given treatments that will benefit them the most.
Got the genes like Jagger
Continuing on the topic of genetics, we then delved into epigenetics and inherited breast cancer risk.
Dr James Flanagan, a former Breast Cancer Now scientific fellow, took us on a tour of all things epigenetics. Epigenetic changes are molecules that sit on top of our DNA and alter how it’s read but don’t change the code itself. Dr Flanagan reminded us that epigenetic changes can vary over time, giving the example of Mick Jagger whose epigenetics probably reflect years of smokes, drink and rock ‘n roll.
Dr Flanagan’s team has identified some of the first evidence that epigenetics can affect women’s risk of developing breast cancer. His team are now looking in more depth at the link between epigenetics and breast cancer risk, including how epigenetic changes and inherited genetic changes might interact to affect risk.
Talking of inherited genetic changes, we now know about more than 90 tiny genetic changes, or variants, that have a small effect on breast cancer risk on their own, but can have bigger effects when you inherit many variants, or certain combinations.
Prof Paul Pharoah gave us a heads up that he and colleagues will be publishing evidence of even more genetic variants in the near future. These results are thanks to a big international collaboration, which includes data from the Breast Cancer Now Generations Study.
Researchers are now trying to get our knowledge about these 90+ genetic changes into the clinic to help us better predict women’s risk of the disease, one example being a current trial in Manchester.
There were great question from patient advocates throughout the symposium and after several mentions of EU funding on Friday morning the questions were rather topical.
The mega impact of the microenvironment
Moving away from genes in a cancer cell to the environment outside and surrounding the cell we then received an update on microenvironment. This is the local environment around and amongst tumour cells, the relationship with non-cancer cells here being complex and dynamic.
Prof Carsten Denkert talked about immune cells in the microenvironment called tumour-infiltrating lymphocytes (TILs), which may be used to predict how breast cancer patients will respond to treatment. Studies so far have suggested that tumours with a greater number of TILs are associated with better outcomes for patients.
Also found in the microenvironment are cells called fibroblasts, which undergo changes that help cancer cells to grow. Dr Fernando Calvo updated us on his work uncovering what causes these changes and looking for ways to reverse them.
Is winter coming for cancer?
Another feature of the tumour environment is that it often has low oxygen levels (known as hypoxia), and Prof Adrian Harris ended the day discussing how this can benefit cancer cells by leading to drug resistance and poorer outcomes for patients.
As we’ve previously reported, Prof Harris has found that tumour cell growth can be reduced by preventing cells from adapting their metabolism in response to hypoxia. He’s also identified a drug which can stop several genes, known to encourage cancer progression, from being switched on.
To round up both his talk and our first day at the symposium, Prof Harris used the audiences knowledge of Game of Thrones ***spoilers ahead*** to show how cancer cells are kept alive and supported by a host of other cells in the body. Much like the resurrection of Jon Snow, apparently.
As the laughter died down and people made their way out into the London sunshine we looked forward to another day of super science on Saturday. Make sure you head back tomorrow to read more about Saturday’s talks on “cancer judo” and more…