Researchers have identified a gene which could provide new routes for breast cancer treatment. 

Scientists from the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR), London and the Breast Cancer Now Research Unit at King’s College London, have uncovered a new weakness in triple negative breast cancer linked to a gene called HORMAD1. 

The HORMAD1 gene is normally only switched on in cells involved in reproduction in the ovaries and testes and remains inactive elsewhere in the body. The gene is responsible for ensuring the genetic information is distributed properly in sperm and eggs. 

However, in some cancers, including 60% of triple negative breast cancers, the HORMAD1 gene becomes active out of context. A study, published in Nature Communications, shows that when the HORMAD1 gene is active in triple negative breast cancer cells, it disrupts a key safety mechanism. 

The research could help treat triple negative breast cancer in new ways, a type of cancer that makes up around 15% of breast cancers. This form can be more aggressive and harder to treat than other forms of the disease and is more common in women with an inherited altered BRCA gene, women under 40 years of age, and black women.  

“Although this research is still in its early stages, it offers an important step forward in understanding triple negative breast cancer and opens the door for the development of new treatments,” said Professor Andrew Tutt, Director of the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London, Director of The Breast Cancer Now Research Unit at King’s College London and corresponding author of the study. 

“It also highlights that testing for the activity of the HORMAD1 gene in triple negative breast cancer could guide treatment decisions in the future. Together, these insights bring us closer to developing more precise therapies for people with triple negative breast cancer.” 

‘Most promising’ therapeutics should be progressed to trial

In the study, researchers identified several drugs currently being investigated as cancer treatments that could be effective against triple negative breast cancer cells with the active HORMAD1 gene. 

The researchers tested whether blocking Aurora B, MPS1 and BUB1 proteins stopped the growth of cells with the active HORMAD1 gene in the lab. They also looked at whether two Aurora B inhibitors, currently in early-stage clinical trials, worked to treat mice carrying human triple negative breast cancer tumours with the active HORMAD1 gene.  

The treatment successfully reduced tumour growth, further validating their findings. The team will now investigate the possibility of developing drugs that target Aurora B, MPS1 and BUB1 for patients with this type of breast and possibly other cancers. 

“Each year, around 8,000 UK women are diagnosed with triple negative breast cancer and it’s more likely than most other breast cancers to return or spread during the first years following treatment,” said Dr Simon Vincent, Chief Scientific Officer at Breast Cancer Now. 

“There are also fewer targeted treatments available, so it’s vital we find new and effective ways to tackle this devastating disease. The findings open the door to the next crucial phase of research, where the research team can identify and test the most effective drugs or drug combinations against triple negative breast cancer with an active HORMAD1 gene, and move the safest and most promising options towards clinical trials.”