BioWorld International Correspondent
LONDON - Tumors in women who have the most common inherited form of breast cancer are significantly more likely to express one or more of a group of proteins called basal keratins, researchers in the UK have found.
The discovery raises the hope that it might be possible to develop a test that could be widely used to identify women with inherited breast cancer caused by the BRCA1 mutation. The unusual pattern of protein expression also could help researchers to identify new drug targets to treat women with that type of tumor.
Scientists at the Cancer Research UK Genetic Epidemiology Unit in Cambridge said that the finding could be used to test the tumors of women who recently have been diagnosed with breast cancer. They are planning further studies to determine which combination of the proteins correlates best with the gold-standard diagnosis of BRCA1 status by genetic testing.
Doug Easton, professor of genetic epidemiology at the unit, told BioWorld International: "This finding may provide a way of identifying those patients with the inherited form of breast cancer more easily, even in those who do not have a family history of the disease. It also confirms that there is something different about BRCA1 tumors, which has the potential to lead us on to different ways of treating this disease, including different drug targets."
One of those targets, he suggested, might turn out to be epithelial growth factor receptor. That protein is among those expressed in the BRCA1 tumors; drugs that target it already are under development.
Women who carry a faulty BRCA1 gene have an 80 percent chance of developing breast or ovarian cancer during their lifetime. Those with breast cancer who have the mutant BRCA1 gene have a 50 percent risk of developing a second breast cancer, and they also have a 40 percent risk of developing ovarian cancer.
Among the general population of women with breast cancer, however, only 1 or 2 percent have the faulty BRCA1 gene.
Studies using expression arrays to find out which proteins are expressed in different types of cells had suggested that the tumors that develop in women with the BRCA1 mutation tend to express proteins known as basal keratins.
Easton and his colleagues decided to use that information to design a study to find out if they could detect such proteins by staining biopsy specimens. Working with Cancer Research UK scientists from Leeds and Manchester, as part of a worldwide collaborative study, they tested more than 200 breast tumors for a specific set of basal keratins.
They found five markers that were strongly correlated with carrying a BRCA1 mutation. One of these, CK5/6, was present in 56 percent of all BRCA1 gene carriers, compared to about 7 percent of tumors from women with breast cancer who were not known to be BRCA1 carriers.
The study is reported in the Aug. 9, 2005, issue of Clinical Cancer Research in a paper titled "Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype."
Easton said: "In women with the BRCA1 mutation, the tumors are almost always oestrogen-receptor negative. So this basal' type of tumor is a subset of oestrogen-receptor negative tumors. In contrast, in the population of breast cancer patients as a whole, most tumors are oestrogen-receptor positive and only a few express basal keratins."
In the short term, the scientists will aim to replicate the results on a larger scale. Easton said, "There are several different markers that correlate with the basal keratin phenotype, and we need to work out the best combination that correlates most closely with BRCA1 status."
In the future, the scientists would like to invite women who have been recently diagnosed with breast cancer to have the new test. The researchers want to know how well they can identify individuals whom they think are carriers of BRCA1 using the new test, and then check if they are right with the existing genetic test for BRCA1.
Easton added: "We also need to know what the patients will think of this. At present, most patients who are tested for BRCA1 have a strong family history of breast cancer and they want to know their status. We need to know how a test would be received by women with breast cancer in general, as the result will have implications both for them and for members of their families."