Genetics and stem cells

New breast cancer genes probed

Researchers have found three more genes linked to the most common form of breast cancer, The Daily Telegraph has reported. The newspaper said the finding could lead to new ways of diagnosing and treating ‘oestrogen receptor positive’ breast cancer, the hormonally responsive form that accounts for four out of five cases of breast cancer.

The story is based on research which has identified three genes that are located directly next to the oestrogen receptor gene, the main driver of hormonal breast cancer. All three genes were found to be linked to the oestrogen receptor gene, although their behaviour is independent of it. The scientists say the newly discovered genes may influence the behaviour of breast cancer and may therefore be the target of future cancer therapies.

While the findings are of note, it is important to stress it is still uncertain if or how the identified genes influence the behaviour of oestrogen responsive breast cancer cells. As such, this preliminary research will not immediately influence the current treatment of women with the cancer, which currently involves using drugs such as tamoxifen that target oestrogen and the oestrogen receptor. As the scientists note, the discovery could lead to new treatments for this type of breast cancer, although only with development through further research.

Where did the story come from?

The study was carried out by researchers from the Royal Marsden Hospital and the Institute of Cancer Research, London. It was funded by the Mary-Jean Mitchell Green Foundation, Breakthrough Breast Cancer and the NHS. The study was published in the peer-reviewed journal, PLoS Genetics.

Generally the national media reported the story accurately, although most newspapers reporting on the study seemed to base their articles on the content from the accompanying press release, reproducing the slightly cryptic comment that the discovery was ‘like finding gold in Trafalgar Square’.

The Daily Mail made assertions the research could lead to new drug treatments within five years and that thousands of lives could be saved, although these specific claims are not supported directly by this research, and would only be achieved with a great deal of additional research into, as yet, undeveloped therapies.

What kind of research was this?

This laboratory study looked at breast cancer cells taken from 104 patients with ‘oestrogen receptor positive’ breast cancer. This is a type of breast cancer where the cancerous cells are stimulated by the presence of the female hormone oestrogen due to them possessing receptors for the hormone. The researchers wanted to identify any gene variants that were closely linked to ESR1, the main gene that governs the oestrogen receptor in the human body.

The researchers point out that about 80% of all breast cancers are of this type, which is known to respond to anti-oestrogen therapy, such as the commonly used drug tamoxifen. They say recent genome-wide studies have revealed that the way in which genes are arranged on chromosomes is crucial in determining the way these genes behave, and that it has been discovered that certain ‘clusters’ of genes are regulated together.

Studies have also suggested that genetic variants lying outside of the main oestrogen receptor gene are linked to breast cancer risk. This suggests there may be other genes that also influence the risk of oestrogen receptor positive breast cancer and the course of the disease. These genes could therefore be targets for future treatment.

What did the research involve?

The researchers looked at molecules from tumour biopsies taken from 104 postmenopausal women with oestrogen receptor positive breast cancer. This was done both before and after the women had had two weeks of treatment with a type of drug called an aromatase inhibitor, which blocks oestrogen production.

The researchers first extracted a type of genetic material called RNA (ribonucleic acid) from the tumour samples and then used standard techniques to ‘amplify it’ (increase the amount of RNA available for testing). They analysed the amplified RNA, particularly looking for the statistical links or correlations between the ESR1 gene and genetic mutations called single nucleotide polymorphisms (SNPs) in the surrounding genetic code.

They also looked at where these SNPs were located, that is, whether they lay in genes with a specific function, and further tested for the biological effects of these genes.

What were the basic results?

The scientists located three previously uncharacterised genes ‘immediately upstream’ of ESR1, that is, in the genetic sequence immediately surrounding the ESR1 gene. These were called C6ORF96, C6ORF97, C6ORF211. They found that while these genes were closely linked to the oestrogen receptor gene, they were working separately from it.

They then studied the potential biological effects of these genes. They found that C6ORF211 appeared to drive the growth of tumours and C6ORF97 appeared to be an indicator of a tumour not coming back, as well as a good predictor of response to tamoxifen. Less was discovered about the function of C6ORF96.

How did the researchers interpret the results?

The researchers say their observations suggest some of the biological effects previously attributed to the ESR1, the oestrogen receptor gene, could be mediated or modified by these co-expressed genes.

Professor Mitch Dowsett, who led the research, said in an accompanying press release that the research shows that “while the oestrogen receptor is the main driver of hormonal breast cancer, there are others next door to it that also appear to influence breast cancer behaviour. We now need to better understand how they work together and how we can utilise them to save lives of women with breast cancer.”

Because C6ORF211 appears to drive the growth of tumours, the team sees this as the most likely target for new treatments.


This preliminary finding is of interest because it has located three genes very near the ESR1, the main gene to influence the behaviour of breast cancer cells, and which appear to be connected with the actions of ESR1 in some way.

However as the researchers note, further work needs to be undertaken into the behaviour of these genes, to see if or how they influence the risk and also course of the disease. It is possible that one or all of these genes could be targets for new therapies to prevent and treat breast cancer treatments in the future, but substantial research is required to develop the new, experimental treatments first and then to ascertain whether safe treatment or prevention is possible.

NHS Attribution