New research from our scientists has revealed a weakness in triple negative breast cancer cells linked to a gene typically only active in reproductive cells. Targeting this gene may hold the key to new treatments for this breast cancer subtype.
In this section
Scientists from the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, 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 findings, published today in Nature Communications, provide new understanding of triple negative breast cancer. The researchers hope their discoveries will increase our ability to personalise therapies and improve the effectiveness of breast cancer treatment.
Understanding the problem
Triple negative breast cancer accounts for around 15% of breast cancer diagnoses. It’s more common in women with an inherited altered BRCA gene, women under 40 years of age and black women.
We call it triple negative breast cancer because its cells lack oestrogen receptors, progesterone receptors and HER2 proteins. This means that hormone therapies and -targeted drugs commonly used to treat other breast cancer subtypes don’t work.
And while targeted therapies like and can be used to treat certain triple negative breast cancers, they don’t work for everyone. So we urgently need to find better treatments.
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. There are also fewer targeted treatments available, and a lot of people rely on chemotherapy, so it’s vital we find new and effective ways to tackle this devastating disease.
Dr Simon Vincent, chief scientific officer at Breast Cancer Now
Revealing a hidden weakness
In this study, led by Dr Stephen Petitt and Professors Andrew Tutt and Chris Lord, they investigated the role of a gene called HORMAD1. This gene is normally only switched on in cells involved in reproduction -the ovaries and testes - and remains inactive in cells elsewhere in the body.
But in around 60% of triple negative breast cancers, HORMAD1 turns on in breast cells when it shouldn’t. And when this happens, it disrupts a key checkpoint that makes sure cells divide without errors in their DNA.
In experiments on cells grown in the lab and in mice, the researchers uncovered a series of events and key proteins related to HORMAD1 gene activity. This causes the cancer cells to become unstable, resulting in DNA damage and errors in DNA being passed onto new cancer cells.
But if too much of this DNA damage occurs, even the cancer cells cannot survive. So the cancer cells instead have to rely on alternative pathways for DNA repair.
This reveals a weakness in triple negative breast cancer cells with an active HORMAD1 gene, as researchers can develop treatments that target the alternative repair pathways leading to a build-up of DNA damage that kills the cancer cells. We call this synthetic lethality.
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. 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.
Professor Andrew Tutt, Director of our Research Centre at The Institute of Cancer Research, London
The team tested whether blocking three proteins, Aurora B, MPS1 and BUB1, could stop 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. Promisingly, the treatment was able to successfully reduce tumour growth in these mice.
Looking to the future
Triple negative breast cancer currently lacks targeted treatments. But the more we find out about the disease, the more likely we are to find better treatments.
When you’re diagnosed with a type of breast cancer that has fewer treatment options and a higher risk of coming back, it’s hard not to live with constant uncertainty about the future. Knowing that scientists are finding new ways to understand this aggressive disease, and working towards more targeted treatments, means so much to me and gives me real hope for the future.
Liz Boughton, diagnosed with triple negative breast cancer August 2024
This exciting research has revealed a number of potential new drug targets, and we now need to test and understand these further to see if they could lead to new treatments in the future.
Every year in the UK, over 8,000 people are diagnosed with triple negative breast cancer and 60% of these will have an active HORMAD1 gene. With further work, this research has the potential to help thousands of people diagnosed with this aggressive form of breast cancer.
Incredible research like this is only possible thanks to the incredible generosity of our supporters. The Breast Cancer Now Research Unit at King’s College London is supported by the Asda Tickled Pink campaign and Omaze is the flagship funder of the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London.
Triple negative breast cancer research
Our research unit at King's College London is entirely focused on studying triple negative breast cancer. 15 scientists all working together to find what drives it, where its weaknesses lie and how to develop new treatments.