Reproduction and Fertility is an open-access, peer-reviewed journal
Page URL: https://www.bionews.org.uk/page_93002

Study finds key genes involved in aggressive form of breast cancer

6 June 2011
Appeared in BioNews 610

Scientists have identified a set of 15 genes that are associated with triple-negative breast cancer (TNBC), an aggressive form of the disease that does not respond to the drugs commonly used to treat other types of breast cancer.

TNBC accounts for a fifth of all breast cancer cases, and is more common in younger patients, African-American patients and patients with the BRCA1 gene mutation. Approximately 9,000 women are diagnosed with TNBC in Britain each year. Patients with TNBC have a poorer prognosis than women with other types of breast cancer, and have a higher rate of cancer recurrence.

TNBC tumours are known to contain many stem cell-like cells – rapidly-dividing and immature cells. They also lack the molecular receptors – oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) that are the normal targets of many breast cancer drugs. These drugs are consequently ineffective in TNBC patients.

In the new study, researchers at the Dana-Farber Cancer Institute, affiliated to Harvard Medical School in the US, aimed to identify genes associated with TNBC that could be used as new targets for drug development. By analysing patterns of gene activity in 587 TNBC breast cancer tissue samples from publicly-available datasets, the researchers were able to categorize TNBC tumours into six distinct subtypes based on their unique gene activity profiles.

They identified a set of 15 genes that are required for cell growth in TNBC tumours. These genes are associated with a cell 'signalling pathway' known as Jak2/Stat3. In laboratory tests, TNBC tumour cells were treated with drugs known to block the Jak2/Stat3 signalling pathway, and the researchers found that the drugs suppressed cell growth. The drugs were also effective in suppressing the growth of TNBC tumours in mice.

The research team believes these findings will have immediate clinical implications for TNBC patients. 'The discovery of these targets will rapidly lead to clinical trials with the hope of achieving one of the first specific therapies for triple-negative breast cancers', said Dr Kornelia Polyak, from the Dana-Farber Institute.

The Jak2/Stat3 signalling pathway is known to be involved in certain blood cancers. Two drugs that inhibit this signalling pathway are already in advanced clinical trials, with another three at earlier stages of drug development. The researchers are now beginning clinical trials for one of these drugs in TNBC patients, and estimate that up to 50-60 percent of TNBC patients have an 'abnormally activated' Jak2/Stat3 pathway that may be responsive to this drug treatment.

The researchers also hope to identify 'biomarkers' based on the gene activity profiles of the six TNBC subtypes that could be used to classify breast cancer tumours in patients, and indicate which targeted therapies are likely to be most effective for each person.

Dr Caitlin Palframan, policy manager at Breakthrough Breast Cancer, said: 'This research is very exciting as new treatments for triple-negative breast cancer are urgently needed. There are limited treatment options available for this group of patients so a targeted treatment would be a real breakthrough. However, this is early-stage research in mice and we look forward to seeing if this approach will prove effective in the upcoming clinical trials'. 

The study was published in the Journal of Clinical Investigation.

SOURCES & REFERENCES
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies
Journal of Clinical Investigation |  06/11
Overactive gene could provide key to treating one of deadliest breast cancers
Daily Mail |  2 June 2011
Triple-negative breast cancer: drug trial to start
Daily Telegraph |  2 June 2011
RELATED ARTICLES FROM THE BIONEWS ARCHIVE
5 December 2011 - by Dr Zara Mahmoud 
Two new gene variants, which each increase the risk of bone marrow cancer by 30 percent, have been identified by scientists at the Institute for Cancer Research...
5 December 2011 - by Sarah Pritchard 
Two gene rearrangements associated with prostate and lung cancer could also be behind five to seven percent of all breast cancers, according to US scientists...
5 September 2011 - by Dr Vivienne Raper 
UK women at high risk of breast cancer could halve their chances of developing the disease with genetic risk testing during routine NHS screening. This news came from PROCAS - the world's first study into giving genetic risk and prevention advice in a national breast screening programme, and was reported in this Sunday's Express....
22 August 2011 - by Heidi Colleran 
Two US studies published this week have shed light on how a gene mutation can change the number of chromosomes present in the cells of more than 90 percent of cancers...
17 May 2010 - by Dr Tamara Hirsch 
Five new genetic variants have been discovered which, in combination, raise the risk of developing breast cancer by 16 per cent, according to a new study in Nature Genetics...
22 March 2010 - by Dr Rachael Panizzo 
Breast cancer risk prediction does not improve significantly when genetic information is included in the risk prediction model, a new study published in the New England Journal of Medicine has found....
12 October 2009 - by Sarah Pritchard 
Scientists have discovered a gene which links half of all breast cancers and when damaged, may be responsible for allowing the disease to develop and grow. The researchers noticed that parts of chromosome 8 were missing from tissue which had been removed from 54 breast cancer patients. When they compared the missing area against the information from the Human Genome Project, they discovered it was the NRG1 gene which had been lost....
5 October 2009 - by Dr Jay Stone 
Edwina Hart, the Welsh Assembly Minister for Health and Social Services, has said that some women in Wales at increased risk of developing hereditary breast cancer are having to wait up to three years to get their genetic test results, while English women are waiting only eight weeks....
6 April 2009 - by Lorna Stewart 
Research published last week in Nature Genetics reports the discovery of two new genes which alter a woman's risk of developing breast cancer. The study, led by Cancer Research UK, was a collaboration between more than 100 scientists across 16 countries. It brings the total number of...
HAVE YOUR SAY
to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions


Syndicate this story - click here to enquire about using this story.