WEST AUSTRALIAN researchers have discovered the cause for the deadliest type of breast cancer which kills half of all people diagnosed with it.
The cancer-causing gene which causes a highly-aggressive breast cancer has been identified by Perth-based scientists who hailed the breakthrough as a "significant discovery". There are hopes it could lead to a dramatic improvement in outcomes for patients diagnosed with this treatment-resistant breast cancer.
The research also suggests the newly discovered cancer-causing gene protects the tumour from regular cancer treatments and that the treatments commonly used actually trigger the cancer to grow.
The discovery came after eight years of work by a team at Harry Perkins Institute of Medical Research in Perth. The researchers were looking into hormone-sensitive breast cancers, which make up about 75 per cent of all breast cancers, which typically have a high survival rate.
In the course of their research, the scientists discovered a previously uncharacterized group of hormone-sensitive cancers that are very aggressive with poor survival in affected patients.
Upon further examination, they pinpointed a novel cancer-causing gene that produces large amounts of a unique protein called AAMDC which triggers tumour growth in a sub-group of hormone-sensitive breast cancers.
It was discovered that standard hormone treatments for this type of breast cancer fail to kill the tumour cells and could in fact promote tumour growth and worsen survival in affected patients.
"Hormone-sensitive breast cancers usually have better outcomes than the hormone-resistant ones, such as triple negative breast cancer," said lead researcher, Associate Professor Pilar Blancafort, head of Cancer Epigenetics at Harry Perkins Institute of Medical Research.
"However, 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.
"When we look at these cancers, we find that they are bigger, tend to spread more commonly to lymph nodes and have a higher death rate. What we needed was to find a way to identify them and then to treat them."
Protein 'protects' cancer cells
The team began by taking data from an American study looking at thousands of breast cancers.
They then picked those hormone-driven cancers with the worst chance of survival and looked at how they were different from cancers with better outcomes.
"By analysing this sub-group, we discovered these aggressive cancers have extra copies of a particular oncogene, (cancer causing gene). The cancer cells use this multiplied gene to make a cancer-driving protein (AAMDC) at higher than normal levels."
"This copying or amplification of the gene that makes the AAMDC cancer driving protein is found on a particular chromosome - chromosome 11 - in about 10 per cent of all breast cancers. It is also present in other cancers, such as ovarian, prostate and lung cancers.
"Importantly we can now find these cancers by looking for high levels of AAMDC in the tumour cells."
Associate Prof Blancafort said the AAMDC protein is unique, in that it has a different shape and structure to all other proteins so far discovered in the human body.
"In fact, the shape or folding of the new protein most closely resembles a protein found in bacteria, rather than in human cells. Its unique shape suggests that the protein does a different job in normal human cells than all other proteins found so far."
She said what is also unusual is that the protein promotes the growth of cancer, but not it is not under the control of estrogen and progesterone, the hormones in breast tissue which are typically the major controllers of cell growth.
"As a result this cancer protein can protect the tumour cells against anti-cancer hormone treatments, preventing the cancers from being cured.
"We discovered that the AAMDC protein can reprogram breast cancer cell metabolism, making the cells more adaptable when food and energy supplies are low. It can also activate new growth pathways in the cell which allow increasing growth and division when estrogen is removed or even when cancer cells are placed in presence of anti-estrogens.
"Usually starving hormone receptive breast cancers of estrogen causes them to shrink, but in this sub-group starving them of estrogen triggers a signal that causes the tumour to grow.
"In other words, AAMDC can protect cancer cells from dying and maintain their growth when the tumour is placed in conditions where scarcity of nutrients or starvation of estrogen growth signals would kill most hormone sensitive cancers.
"Therefore, we believe the cancer promoting function of AAMDC is to act as a 'survival kit', allowing tumours to adapt to these conditions supporting the growth and multiplication of breast cancer cells in conditions of metabolic stress."
She said by using new drugs, which block the pathways AAMDC switches on to allow cancer cell survival, doctors may be able to both kill these cancer cells directly as well as restore their sensitivity to usual hormone treatments.
"Hopefully this will dramatically improve the poor outcomes these patients currently suffer. This is the significant discovery."
The research was published in Nature Communications.
Geraldine Cardozo
Features Editor at The Senior.
Features Editor at The Senior.
