Working initially in mice, Dr Cryns and colleagues found that aB-crystallin promoted brain metastasis in aggressive "triple-negative" breast cancers that lack expression of three different receptors, the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2).
Based on these earlier findings, Dr Cryns turned to an international team of scientists to examine whether levels of aB-crystallin in breast tumour samples could help identify those patients who would go on to develop metastasis to the brain.
The team analysed nearly 4,000 breast tumour samples from women with long-term clinical follow up, including sites of metastasis.
The researchers found that among women with metastatic disease, women whose breast tumours expressed aB-crystallin were nearly three times more likely to develop brain metastasis than women whose breast tumours did not express this protein.
The aB-crystallin expression also predicted shorter survival after the initial breast cancer diagnosis and after the diagnosis of brain metastasis.
"The results were completely consistent with our predictions based on our prior laboratory studies," said Dr Cryns.
"Our hope is that this test will become a useful biomarker to identify breast cancer patients at high risk for brain metastasis so that they could be monitored more closely or enrolled in trials of new agents to prevent brain metastasis.
"In addition, our lab is working on strategies to therapeutically target aB-crystallin as a strategy to treat or prevent brain metastasis in breast cancer," said Dr Cryns.
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