Predicting breast cancer progression and personalising treatments

When breast cancer spreads and grows into tumours in other parts of the body, we call this secondary breast cancer. And although it can be treated, it’s currently incurable. Breast cancer is more likely to spread if it stops responding to treatments.

One of the major challenges is knowing which breast cancers will spread, and which tumours will resist treatments. If we could predict this, we could help personalise treatments to prevent secondary breast cancer for people most at risk. 

Nick’s research involves developing tests that can pick up very small amounts of cancer DNA in the blood, called circulating tumour DNA (ctDNA). These tests are also known as liquid biopsies. They have the potential to:

• Help us detect cancer coming back before scans can pick up secondary breast cancer
• Detect changes in cancer cells that indicate if treatment resistance is likely to happen
• Inform doctors about personalised treatment opportunities based on the features of cancer cells

Nick and his team are focusing on 4 main projects:

1. Using liquid biopsies to diagnose and predict relapse  
   
   By studying tumour samples and ctDNA from blood donated by people with breast cancer, Nick’s team is investigating which genes are turned on and off in breast cancers.
   
   They hope to identify signs, or biomarkers, of disease progression in the samples. These could then be used to inform clinicians how likely a tumour is to grow back, spread and resist treatment. 
   
   In the future, a doctor could test blood samples for these biomarkers – and the person with breast cancer could get the best treatment earlier, when it can be more effective.
   
   
   
2. Tracking how breast cancer changes over time
   
   Nick’s previous work tested a combination therapy of 3 types of drugs – CDK4/6 inhibitors, PI3K/AKT inhibitors, and hormone therapy. He found that this combination more than doubled the length of time before the cancer progressed, compared to a targeted treatment currently on the NHS. And final analysis showed that overall, people survived 7 months longer. 
    
   Now they want to improve the effectiveness of this treatment. To tackle treatment resistance, they’re tracking what genes the breast cancer turns on and off during the triplet therapy to evade it. By doing this, they can identify any signs of treatment resistance. They can then look for ways to overcome treatment resistance by selecting the most suitable next drug.
    
   If they can find these biomarkers early in the treatment journey, they may be able to predict which tumours will become resistant. In the future, this information could lead to improved treatment plans, where people with resistant tumours are offered a different, more effective treatment. 
   
   
3. Improving liquid biopsies to monitor ER-positive breast cancers
   
   Breast cancers that use the hormone oestrogen in the body to help them grow are called ER-positive. They are treated with hormone therapy. But for treatment to be effective, the breast cancer cells must continue to rely on oestrogen for growth. 
   
   Currently, the only way to know if a breast cancer is still reliant on oestrogen is to take a tumour biopsy. But biopsies are invasive, and we can’t use them to monitor the disease over time.
   
   So, the team want to improve their blood test to measure how dependent the breast tumour is on oestrogen in a non-invasive way. In the future, this test could be used to determine if the hormone therapy is still the most suitable treatment.
   
   
4. Overcoming resistance to AKT inhibitors
   
   Capivasertib, an AKT inhibitor, is used in combination with a hormone therapy drug called fulvestrant to treat some ER-positive secondary breast cancers. But it’s not always effective. Nick and his team want to understand how breast cancer can resist this treatment. 
   
   First, they are studying ER-positive breast cancer cells in the lab to identify what genes turn on and off when the cancer cells resist the treatment. Then they’ll study these genes in samples donated by people with breast cancer whose breast cancer has resisted therapy.
   
   In the future, this could lead to new drug targets that could improve effectiveness of drugs like capivasertib, allowing more people to benefit from the treatment.
   
   

The team’s research could tackle treatment resistance and allow more people to benefit from drugs that are currently available. 

Liquid biopsies could revolutionise how breast cancer is diagnosed and treated, allowing people to receive the most suitable treatments. They could also allow people to switch treatments as soon as there’s a sign that their breast cancer is starting to show treatment resistance.

This could give more precious time to people with incurable secondary breast cancer. And it could help to successfully treat more people with primary breast cancer too. 

Up to 44,000 people are diagnosed with ER-positive breast cancer each year in the UK. This project could help each one of them.  And liquid biopsies could help every person with diagnosed with breast cancer – that’s 55,000 people each year.