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Changes can be detected in BRCA1 breast cells before they turn cancerous

last modified Mar 09, 2021 02:20 PM
Researchers may have found the earliest changes that occur in seemingly healthy breast tissue long before any tumours appear, according to a new study published in Nature Communications today...

The study, funded by Cancer Research UK, showed that before becoming cancerous, breast cells with the BRCA1 gene mutation undergo changes similar to those normally seen in late pregnancy.

Although this is early research, in the future, doctors could screen women with BRCA1 mutations to monitor changes to their breast cells, which could help inform who might benefit from preventative surgery, and to give reassurance to those who can wait.

BRCA1 mutations significantly increase the risk of developing breast cancer at a younger age. Many women who discover they carry the faulty gene choose to have a preventative mastectomy*.

Not all women who have BRCA1 mutations will go on to develop cancer so for some, this life-changing surgery may be unnecessary, or could at least be delayed until early warning signs are spotted.

Researchers led by Karsten Bach and Dr Sara Pensa at the University of Cambridge wanted to develop a method to detect the early changes occurring in BRCA1-affected breast cells indicating that they are progressing towards breast cancer.  

The team analysed the mammary tissue of 15 mice at various ages carrying the BRCA1 mutation to look for changes in the tissue that were happening before the mice developed tumours.

The researchers found that having a BRCA1 mutation triggered certain pathways to be switched on in a type of stem cell called a luminal progenitor breast cell that are only activated during pregnancy. These messages tell the progenitor cell to turn into alveolar cells, which make up the chambers in the breast where milk-production takes place during late pregnancy.

Karsten Bach, co-author on the study and PhD student at the Department of Pharmacology and Cancer Research UK Cambridge Institute, said: “We thought we’d been given the wrong mice at first. Then we realised that having the BRCA1 mutation seemed to cause the cells in their breast tissue to behave as if the mouse was pregnant.

“The changes we saw happened very early on before any tumours were detected, so we reasoned that markers of these cellular changes could be used to monitor people who we know are at increased risk for breast cancer.”

Next the team analysed breast cells from 12 women who had a BRCA1 mutation and had undergone a preventative mastectomy.

Surprisingly, the team found that only 4 out of the 12 women had detectable levels of these markers of early stages of tumour initiation. This suggests that the majority of women may have been at lower risk of already being on the path towards tumour development when they had the surgery.

Dr Sara Pensa co-author and Senior Research Associate at the Department of Pharmacology and Wellcome-MRC Stem Cell Institute, said: “One of the mysteries surrounding BRCA gene mutations is how they increase a woman's risk of cancer so dramatically in the breast tissue, as opposed to say the kidneys or lung. It seems that certain pathways in breast cells that are usually switched on by hormones during pregnancy are triggered by BRCA1 mutations and cause the cells to grow out of control.”

Although this is early work and larger clinical trials will be needed, the researchers hope to build on their findings and develop a blood test to detect the early changes occurring in BRCA1 breast cells.

Researchers say in the future, doctors could screen at-risk women with BRCA1 mutations, and help them have informed conversations with women about their risk, guide decisions about preventative surgery, and to give reassurance to those considered not to need surgery at that time.

Michelle Mitchell, chief executive for Cancer Research UK, said: “The discovery of BRCA mutations gave much needed answers to families with a strong history of breast cancer. However, for women that carry the BRCA mutation that are yet to develop breast cancer, they face an incredibly difficult dilemma.  

“This is fascinating research, and we look forward to seeing the next steps, which could mean in the future, doctors could detect if women carrying these mutations have breast cells that are behaving differently. This could make a world of difference, as they may not need preventative surgery until later in life, or even at all.”

 

For media enquiries contact Ellie Bennett in the Cancer Research UK press office on 020 3469 5370 or, out of hours, on 07050 264 059. 

 

Notes to editor:

 

*This involves surgically removing some or all of the healthy breast tissue, which can reduce but not eradicate the risk of developing breast cancer.

About Cancer Research UK

  • Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research.
  • Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
  • Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years.
  • Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK’s ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 years.
  • Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
  • Together with its partners and supporters, Cancer Research UK's vision is to bring forward the day when all cancers are cured.

 

For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1022 or visit www.cancerresearchuk.org. Follow us on Twitter and Facebook.

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