Gene found for deadliest breast cancer

An international research team, including Australian scientists, has discovered a cancer gene responsible for a particularly aggressive breast cancer that is typically resistant to treatment. Their work has been published in the journal Nature Communications.

Led by Associate Professor Pilar Blancafort, Head of Cancer Epigenetics at Perth’s Harry Perkins Institute of Medical Research, the researchers made the discovery after analysing a major collection of data from Stanford, USA, of thousands of breast cancers. Assoc Prof Blancafort said her team looked at the hormone receptor-positive cancers with the worst outcomes and analysed how they were different from cancers with better survival rates.

“Hormone-sensitive cancers make up 70% of all breast cancers,” she said. “They usually have better outcomes for patients than the hormone receptor-negative ones, such as triple-negative breast cancer.

“However, we found a small percentage of patients experience a very aggressive cancer that results in the worst outcomes of all breast cancers, with half of all women dying from the disease,” she said. This group was previously not recognised as a subgroup of hormone-sensitive breast cancers.

“When we looked at these cancers, we found that approximately one out of four women diagnosed with this aggressive disease carry an amplification, or high level, of this gene, and that the presence of the gene is associated with larger tumours, with cancer spread into lymph nodes and with treatment resistance.”

The team discovered these aggressive cancers with extra copies of the cancer-causing gene use this gene to make a cancer-driving protein, known as AAMDC, at higher-than-normal levels. Assoc Prof Blancafort said, “This protein is not like any other protein yet discovered; it is unique. It has a different structure or shape to all other proteins so far discovered in the human body.

“It promotes growth of the cancer, but it is unusual in that it does so independently of the oestrogen and progesterone, the hormones in breast tissue which are typically the major controllers of cell growth in the breast tissue.

“As a result, this cancer protein makes the breast cancer unresponsive to anticancer hormone treatments typically used to treat hormone-sensitive breast cancers.”

The protein can reprogram the metabolism of breast cancer cells, making them more adaptable when cancer treatments starve them of nutrients and energy supplies. Usually starving hormone receptive breast cancers of oestrogen causes them to shrink, but in this subgroup starving them of oestrogen triggers a signal that actually causes the tumour to grow.

“We believe the cancer-promoting function of this protein is to act as a ‘survival kit’, allowing tumours to adapt to conditions during treatment.”

By using new drugs that block the pathways the protein creates to promote cancer cell survival, it may become possible to kill these cancer cells directly and restore their sensitivity to usual hormone treatments.

“Hopefully this will dramatically improve the poor outcomes these patients currently suffer,” Assoc Prof Blancafort said.

Image credit: ©stock.adobe.com/au/Africa Studio

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