Washington, Aug. 3 : The "daughters" of breast stem cells, called luminal progenitor cells, are found to be responsible for breast cancers that develop in women carrying mutations in the gene BRCA1, according to scientists at Walter and Eliza Hall Institute.

Women with BRCA1 mutations often develop "basal-like" breast cancer, which is a particularly aggressive form of the disease.

Led by Associate Professors Jane Visvader and Geoff Lindeman, the researchers have discovered that luminal progenitor cells are the likely source of basal-like breast tumours.

The finding represents a major shift in the way scientists think breast cancer develops.

Visvader said that it had been thought in recent years that breast stem cells gave rise to BRCA1 tumours.

"However, research carried out at the institute by Drs Elgene Lim and Fran
çois Vaillant has shown that breast tissue from women with BRCA1 mutations has unexpectedly high numbers of luminal progenitor cells," she said.

She added: "Further, our gene expression studies have revealed that BRCA1 breast tissue and basal breast tumours are more similar to normal luminal progenitor cells than any other cell type in the breast. This places the spotlight on errant luminal progenitors, rather than breast stem cells."

Lindeman said that now the importance of luminal progenitor cells in breast cancer was known it opened the way for the development of new drugs or therapies to treat breast cancer, one of the biggest causes of premature death in women.

"BRCA1 women have approximately a 65 per cent lifetime chance of developing breast cancer. Following surgery, treatment options available to these women are often limited to chemotherapy and radiotherapy, so identifying new treatment and prevention strategies is a priority for us," he said.

Lindeman said that luminal progenitor cells in women with BRCA1 mutations have 'forgotten' how to behave.

"Usually, luminal progenitor cells multiply rapidly in the presence of certain growth factors. In BRCA1 women these cells don't even require growth factors to proliferate - they misbehave from the outset.

"We also know that the BRCA1 gene is required for normal DNA repair. There may therefore be a triple whammy effect - faulty growth control, faulty DNA repair and expanded luminal progenitor cell numbers -ultimately resulting in breast cancer in some BRCA1 mutation carriers," he added.

Visvader said, in the long-term, breast biopsies might be able to reveal misbehaving luminal progenitor cells.

In fact, certain 'markers' might one day help guide diagnosis and treatment.

"It may even be possible to develop new drugs that target c-KIT, since drugs are already available that target different forms of this marker," said Visvader.

Lindeman said: "Hopefully this will lead to new, tailored therapies for the next generation of women."

The study has been published in the latest issue of the international journal Nature Medicine.