Understanding how hidden breast cancer cells survive treatment

Thanks to research and better treatments over the last 40 years, more people are now surviving oestrogen receptor-positive (ER-positive) breast cancer. But this type of breast cancer can come back many years after treatment. 

We now know that’s because some breast cancer cells don’t die during adjuvant treatment. Instead, they become inactive, or dormant, only to awaken and start growing much later, causing the disease to return.

The researchers plan to use a variety of innovative techniques to detect the dormant cells, as they can be very difficult to detect. They want to examine how hormone therapies impact these cancer cells and find ways to kill them. By doing so, they hope to dramatically reduce the chances of the breast cancer returning.

Treatments kill most breast cancer cells. But some of the cells behave differently – in response to treatment, they enter a reversible, sleep-like state. 

The researchers believe these cancer cells alter the way they behave without changing their genetic code, or DNA. You can think of DNA as a book of instructions for the cell. Instead of changing what’s written in the book, these cancer cells leave notes scribbled in the margins on which information to use and which to ignore. These notes can tell the cell to act in certain ways by interpreting the main written instructions differently. This is what we call epigenetic changes.

The researchers aim to track these epigenetic changes in both breast cancer cells and healthy breast tissue. By understanding how and when cancer cells become dormant via epigenetic changes, they hope to find new ways to get rid of them.

Luca and his team are focusing on 2 main projects:

1. Mapping and targeting dormant breast cancer cells
   

   The team is creating a detailed map of how ER-positive breast cancer cells become dormant during hormone therapy. They’re using tumour samples taken before, during and after treatment, and analysing them with advanced tools that reveal how each individual cancer cell behaves. 

   By analysing epigenetic changes that occur, they aim to uncover what triggers this inactive state to find the weak points in these breast cancer cells. This could lead to new treatments that specifically target and kill dormant breast cancer cells.
   
   The team will also use specially designed mice with cancer cells that closely mimic how ER-positive breast cancer behaves in humans. This will help them test new treatments and see whether they can successfully target and eliminate dormant cancer cells.
   
   
   
   
2. Investigating how healthy breast cells become dormant with age
   

   The researchers are also investigating how some cells become inactive in the healthy breast tissue as women enter menopause. They think this process gets hijacked by some breast cancer cells.

   The researchers believe that as hormone levels drop during menopause, it might contribute to the formation of healthy dormant cells. If this is true, then epigenetic changes may first cause healthy ER-positive cells to become dormant, and then when they wake up, they might turn into active breast cancer cells.
   
   By understanding this process, the team may also find new ways to prevent breast cancer developing in the first place.

This project has the potential to make an enormous difference. If the team can find ways to detect and eliminate dormant cancer cells, this could help stop ER-positive breast cancer coming back. It could also lead to shorter and more effective treatments.

This research may also uncover a new way to stop breast cancer before it even starts.

Thousands – around 44,000 people are diagnosed with ER-positive breast cancer every year in the UK. If we can find a way to eliminate dormant breast cancer cells that remain after treatment is complete, we could significantly reduce the risk of the disease coming back.