Working initially in mice, 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, Cryns turned to an international team of scientists to examine whether levels of aB-crystallin in breast tumor samples could help identify those patients who would go on to develop metastasis to the brain. The team analyzed nearly 4,000 breast tumor 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 tumors expressed aB-crystallin were nearly three times more likely to develop brain metastasis than women whose breast tumors did not express this protein. 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,” says 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,” says Cryns. He cautions that these results need to be validated in additional studies before this test could be used in the clinic.
The research was funded by the Breast Cancer Research Foundation, the US National Cancer Institute, Cancer Research UK and the Canadian Breast Cancer Foundation. Additional scientists involved in the study include co-leader Maggie C. U. Cheang (The Institute of Cancer Research, London, UK), K. David Voduc, Torsten O. Nielsen, and Hagen Kennecke (University of British Columbia), Charles M. Perou and Cheng Fan (University of North Carolina – Chapel Hill), J. Chuck Harrell (Virginia Commonwealth University), and Andy J. Minn (University of Pennsylvania). The study has been published in npj Breast Cancer.
University of Wisconsin School of Medicine and Public Health