Women with BRCA1 mutations could undergo cellular monitoring after scientists discovered key changes can be detected before they become cancerous.
In a mouse study, researchers at the University of Cambridge, UK, found breast cells with the BRCA1 gene mutation undergo changes similar to those normally seen in late pregnancy, long before they develop tumours.
Writing in the latest edition of Nature Communications (9 March 2021), they say monitoring changes to breast cells could help to inform who might benefit from preventative surgery and provide assurance to those who can wait.
The researchers, led by Karsten Bach and Dr Sara Pensa, analysed the mammary tissue of 15 mice carrying the BRCA1 mutation to look for changes in the tissue that occurred before they developed tumours.
They found having a BRCA1 mutation triggered certain pathways to be switched on in the luminal progenitor breast cell, which are only activated during pregnancy.
Co-author Karsten Bach, a 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.”
They went on to analyse breast cells from 12 women who had a BRCA1 mutation and had undergone a preventative mastectomy and found only four out of the 12 women had detectable levels of these markers of early stages of tumour initiation.
This, say the team, suggests the majority of women may have been at lower risk of already being on the path towards tumour development when they had the surgery.
Co-author Dr Sara Pensa, who is a senior research associate at the Department of Pharmacology and Wellcome-MRC Cambridge 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.”
The researchers hope to build on their findings and develop a blood test to detect the early changes occurring in BRCA1 breast cells and say they hope doctors could eventually screen women with BRCA1 mutations, to help them understand their risk and guide decisions about preventative surgery, if it is needed.
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.”
Nature Communications 9 March 2021
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