Researchers have discovered what may be the earliest changes in seemingly healthy breast tissue long before any tumours appear. The study in mice showed that before becoming cancerous, breast cells with the BRCA1 gene mutation undergo changes similar to those normally seen in late pregnancy.
Experts say that although this is early research, in the future doctors could screen women with BRCA1 mutations to monitor changes to their breast cells. This could help inform who might benefit from preventative surgery and reassure those who can wait.
Not all women who have the mutation will go on to develop cancer, and so for some this life-changing surgery may be unnecessary, or could at least be delayed until early warning signs are spotted.
The 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.
They analysed the mammary tissue of 15 mice at various ages carrying the BRCA1 mutation. 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, which are normally only activated during pregnancy.
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These switched-on pathways send messages that 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.
“We thought we’d been given the wrong mice at first,” said Bach, co-author on the study and PhD student at the department of pharmacology and Cancer Research UK Cambridge Institute.
“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.”
Researchers also analysed breast cells from 12 women who had a BRCA1 mutation and had undergone a preventative mastectomy. They found that only 4 out of the 12 women had detectable levels of these markers of early stages of tumour initiation. This 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.
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“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,” said Pensa, co-author and senior research associate at the department of pharmacology and Wellcome-MRC Cambridge Stem Cell Institute.
“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.
The study, funded by Cancer Research UK, is published in Nature Communications.
Reader Q&A: How does radiation kill cancer if it causes cancer?
Asked by: Odysseus Ray Lopez, US
It’s rather like the way guns can be used to commit crime, or stop it. Radiation causes cancer because its high-energy photons can cause breaks in the DNA strands in your cells. Cells can repair this damage up to a point, but sometimes the repair isn’t perfect and leaves some genes defective.
If the break affects one of the many tumour-suppressing genes in your DNA, that cell can become cancerous. But cancer cells are also more vulnerable to radiation than ordinary cells. Part of what makes them cancer cells is their ability to divide rapidly and this normally means that some of the DNA ‘spellcheck’ mechanisms are turned off.
So when a cancer cell suffers a break in a DNA strand, it’s less likely to repair it correctly. Depending where the break occurs, it might either kill the cell outright, or make it reproduce more slowly.
Radiation therapy uses a focused beam that is aimed at just the part of the body with the tumour, and the dose is carefully calculated to cause the minimum collateral damage to healthy cells. Even so, radiation therapy does very slightly increase your chances of developing a second cancer.
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