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Epigenetic Signatures Predict Breast Cancer Aggression

Newly identified epigenetic signatures could help clinicians tell the difference between highly aggressive and more benign forms of triple-negative breast cancer.

A Nature Communications study comparing how DNA is methylated in breast cancer and healthy cells found “distinct methylation patterns” in the primary biopsy breast cancer cells that indicated better or worse prognosis.

Triple-negative breast cancers, which make up 15–20% of all breast cancers, lack any of the three receptors that respond to targeted drugs. Overall, these patients have a higher risk of disease recurrence and shorter survival than those with other breast cancers.

Triple-negative breast cancer patients tend to fall into two categories: those that succumb to their disease within 3–5 years regardless of treatment, and those that remain disease-free for at least 8 years after diagnosis.

At present there is no reliable way to place triple-negative cancers into these two sub-groups, and the outcome of triple-negative breast cancers is far less associated with cancer stage than other breast cancers.

Garvan Institute researchers sequenced and compared archival tissue samples from triple negative breast cancer patients and matched normal samples to determine cancer-specific changes in DNA methylation. “This is the first study to investigate the methylome of triple negative breast cancer – and its association with disease outcome,” said project leader Prof Susan Clark.

Pathologist Dr Glenn Francis, who analysed the tissue samples for the study, agreed. “The information we have at the moment is based on statistics and probability, and we are forced to treat triple negative breast cancer patients as a group, even though we know that they are not a uniform population,” he said.

“By stratifying tumours epigenetically, this study should enable us to track selected groups of patients over time, monitoring how they respond to different treatments.”