Chemotherapy may cause breast cancer to spread, alarming research suggests.
The commonly prescribed chemo drugs paclitaxel and doxorubicin cause breast tumours to release proteins that then circulate in the blood until they reach the lungs, triggering the disease's onset in a new part of the body.
When scientists blocked this protein in a lab model, the cancer did not spread. They hope their findings will help make chemotherapy more effective.
Doxorubicin (stock image) is one of two commonly prescribed breast-cancer chemo drugs the scientists analysed. When put in an experimental tumour model, doxorubicin caused breast tumours to release sacs containing a protein that was then circulated to the lungs
The study was carried out by the Swiss Institute for Experimental Cancer Research and led by Professor Michele De Palma, head of the lab.
Chemotherapy is often given to breast-cancer patients before surgery to shrink their tumours and make them easier to remove.
Known as 'neoadjuvant therapy', this also helps to save healthy breast tissue.
In some cases, chemotherapy can even eradicate the tumour entirely, with such patients being highly likely to remain cancer-free for life.
But the treatment does not always shrink tumours. If the growth resists neoadjuvant therapy, it is more likely to spread to other parts of the body.
Breast cancer affects one in eight women at some point in their lives in both the UK and US, statistics show.
It is unclear how many cases of the disease spread, with the lungs, bones, liver and brain being the most commonly affected secondary areas.
Working with experimental tumour models, the researchers found both paclitaxel - more commonly known by the brand name Taxol - and doxorubicin - or Adriamycin - cause breast cancer tumours to release small fluid-filled sacs called exosomes.
Chemo makes exosomes containing the protein annexin-A6, which is not found in sacs released from untreated tumours.
Paclitaxel - the other chemo drug - causes the same sac to be released from breast tumours, which can then trigger secondary cancer when they reach the lungs.
'It seems that loading of annexin-A6 into exosomes is significantly enhanced in response to chemotherapy,' study author and postdoctoral researcher Professor Ioanna Keklikoglou said.
Once released from tumours, exosomes circulate in the blood until they reach the lungs.
They then give out annexin-A6, which stimulates lung cells to release another protein called CCL2.
CCL2 then attracts immune cells called monocytes, which fight certain infections and help other cells remove dead or damaged tissue.
However, monocytes can also be dangerous, with previous studies showing they fuel the survival and growth of cancerous cells in the lungs.
'In short, our study has identified a new link between chemotherapy and breast cancer metastasis,' Professor De Palma said.
When the researchers neutralised annexin-A6 or blocked the monocytes, the experimental breast tumour no longer spread to the lungs.
They hope this will improve the effectiveness of neoadjuvant therapy.
'Various monocyte inhibitors have been developed for clinical use, so they may be tested in combination with neoadjuvant chemotherapy to potentially limit unwanted side effects mediated by exosomes,' Professor De Palma said.
Although the results are concerning, he urges people not to jump too conclusions.
'While this observation supports the significance of our findings, at the moment we don't know if annexin-A6 has any pro-metastatic activity in human breast cancer,' Professor De Palma added.
The authors also stress their findings should not discourage people from receiving neoadjuvant chemo when it is needed.
'It remains an essential and potentially curative treatment for many invasive breast cancers, as shown by multiple clinical trials,' they wrote.
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