Cancer gene mutation identified

Behind the Headlines

Monday December 10 2007

Picture of woman holding her breasts

BRCA1 mutations account for 5-10% of breast cancers

“New breast cancer hope” proclaims the headline in the Daily Express and other newspapers. Researchers have “identified the deadly combination of genetic mutations in inherited cases of the disease”, the newspaper said.

It has been known for some time that women who carry a dysfunctional BRCA1 gene are at greater risk of aggressive basal-like breast cancer and hence have a poorer prognosis. These women “have an 80 percent chance of developing the disease”, said the Express.

The newspaper stories are based on a laboratory study that gives scientists a better understanding at the level of individual cells of what a mutation of BRCA1 means. Better understanding of the mechanisms that underlie this disease may translate, in time, into new treatments for an aggressive form of cancer that is difficult to treat. However, such treatments are many years away.


Where did the story come from?

Dr Lao Saal from Columbia University in New York and colleagues from other academic and medical departments across Finland, Sweden, Italy and the USA contributed to this research. The study was funded by the US National Institutes of Health, the Department of Defense Breast Cancer Research Program, the Avon Foundation, the October Woman Foundation, the Swedish Cancer Society and several other medical institutes. It was published in the peer-reviewed medical journal Nature Genetics.



What kind of scientific study was this?

This was a laboratory study using mice and human tissue. The researchers were interested in the characteristics of a type of cancer called basal-like cancer. Basal-like breast cancer is common in women who carry a BRCA1 mutation. The BRCA1 mutation is one of the gene mutations that occur in breast cancer where there is a strong family history and women with this mutation have a risk of up to 85% of developing breast cancer


The researchers were particularly interested in a gene called PTEN. When it is working properly, PTEN can stop the growth of tumours, but a mutation of the PTEN gene is less able to control cancer. The researchers looked at mice and noticed that most cancers that developed in mice with mutations of the PTEN gene, were basal-like cancers.

“Our results have important implications for the pathogenesis and treatment of basal-like breast cancer”.

Lao Saal, lead author

To see whether there was a possible link between the type of cancer (i.e. basal-like or not) and PTEN in humans, the researchers looked at breast tumours from 297 women. They compared the differences in PTEN between the cancerous and normal tissues.

It is known that the majority of women with BRCA1 mutations go on to develop basal-like breast cancer, so the researchers also looked specifically at breast tumour tissue from 34 women who were known to have BRCA1 mutations. They were able to see whether problems with PTEN were common or not. Using breast cancer cells grown in the laboratory, the researchers looked at which particular problems with PTEN were associated with BRCA1 mutations in human tissue.


What were the results of the study?

The researchers found there was reduced functioning of the PTEN gene in basal-like tumours, when compared with non-cancerous cells near the tumours. This suggests that there was an association between damage to the PTEN gene and basal-like cancer. This finding was confirmed in women with a known BRCA1 mutation, where 28 out of 34 (82%) tumours showed problems with the PTEN gene. In half of these tumours, it appeared that the PTEN gene wasn’t working at all. The researchers also found that a particular type of problem with PTEN was associated with BRCA1 mutations.


What interpretations did the researchers draw from these results?

The researchers concluded that their study showed that basal-like breast cancer is associated with loss of function of the PTEN gene. As many women with a known BRCA1 mutation are at risk for this type of aggressive cancer, the findings have implications for understanding how their cancer develops. “Our results have important implications for the pathogenesis and treatment of basal-like breast cancer”, the researchers say. 


What does the NHS Knowledge Service make of this study?

This well-conducted study has helped in the understanding of the development of this type of breast cancer. As the authors report, basal-like cancers are aggressive and are more difficult to treat than other breast cancer types.


Although mutations in BRCA1 are rare and account for 5-10% of breast cancers, women who carry the mutation are at high risk of developing breast cancer. These women are also more likely to develop aggressive basal-like cancers. Research that investigates how this cancer develops is useful and the finding that basal-like cancers are linked to a mutation in another gene – PTEN – opens a new avenue for research. However, treatments for basal-like cancer in women with some hereditary types of breast cancer based on this research are a long way in the future.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

New breast cancer hope. Daily Express, December 10 2007

Researchers find breast cancer trigger. The Daily Telegraph, December 10 2007

Scientists isolate faulty cancer gene that triggers the biggest breast tumours. Daily Mail, December 10 2007

Links to the science

Saal LH, Gruvberger-Saal SK, Persson C, et al. Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet 2007; Dec 9 [Epub ahead of print]


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