Test Predicts Whether Breast Cancer Metastasizes to the Brain

Women can live for years with breast cancer that has begun to spread around the body, but the exception is when the cancer spreads to the brain, which usually indicates a woman is in her last few months of life.

The molecular chaperone αB-crystallin is expressed in estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 ‘triple-negative’ breast carcinomas and promotes brain and lung metastasis.

An international team of scientists led by those at University of British Columbia, (Vancouver, BC, Canada) analyzed 969 breast cancer tumors which ultimately spread, or metastasized, to new sites in the body, from a database of almost 4,000 breast cancers from the British Columbia Cancer Agency(BCCA) and 141 had spread first to the brain. The BCCA cohort includes 3,987 formalin-fixed paraffin-embedded specimens from female patients with newly diagnosed, invasive breast cancer referred to BCCA from 1986 to 1992 that were used to construct large tissue microarrays (TMA) linked to detailed clinicopathological data and long-term outcomes with a median follow-up of 12 years.

TMAs were constructed from tissue blocks and αB-crystallin protein expression was evaluated by immunohistochemistry (IHC) using a mouse monoclonal antibody (Enzo Life Sciences; Farmingdale, NY, USA). Tumors were considered positive for αB-crystallin if there was any staining above background levels. The αB-crystallin protein expression was scored by a pathologist who was blinded to clinical outcomes. Samples with less than 50 tumor cells present in the TMA core were excluded from the analysis and the TMAs were digitally scanned.

In the 855Met data set, αB-crystallin gene (CRYAB) expression was an independent predictor of brain as the first distant site of relapse. In the BCCA series, αB-crystallin protein expression was an independent prognostic marker of poor breast cancer-specific survival. Among patients with metastases, αB-crystallin was the strongest independent predictor of brain metastasis and the only independent predictor of brain as the first site of distant metastasis. Expression of αB-crystallin was also associated with worse survival.

Maggie Cheang, PhD, a Senior Staff Scientist and co-leader of the study said, “Spread of breast cancer to the brain is unfortunately very dangerous, and usually leads to death within months. It's important to find new ways to identify women who are most at risk of their cancer spreading to the brain, so that doctors can work out which women might need more intensive or new treatments to try to keep their cancer at bay for longer. Our study linked a positive score in this test with quicker spread to the brain, and importantly showed the factor we were measuring is providing information on patient outcome independently of other biomarkers already measured in the clinic.” The study was published on October 21, 2015, in the journal npj Breast Cancer.

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