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'Daughters' of Breast Cells Likely Source of Breast Cancer Tumors

 
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Researchers have found a population of breast cells, called luminal progenitor cells, to be responsible for breast cancers that develop in women carrying mutations in the gene BRCA1. Their finding, published in the August 3, 2009 issue of the international journal Nature Medicine, represents a major shift in the way scientists think breast cancer develops.

BRCA1 gene mutations are found in 10 to 20 percent of women with hereditary breast cancer. Women with BRCA1 mutations often develop 'basal-like' breast cancer, which is a particularly aggressive form of the disease.

Walter and Eliza Hall Institute scientists have discovered that luminal progenitor cells – the 'daughters' of breast stem cells – are the likely source of basal-like breast tumors.

In recent years scientists have thought that breast stem cells gave rise to BRCA1 tumors. However, research carried out at the Institute has shown that breast tissue from women with BRCA1 mutations has unexpectedly high numbers of luminal progenitor cells.

Studies revealed that BRCA1 breast tissue and basal breast tumors 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.

The identification of stem cells, luminal progenitor cells and other cell types in the breast is now beginning to reveal a breast cancer roadmap - highlighting cancer-prone cell types and key genetic pathways.

The importance of luminal progenitor cells in breast cancer opens the way for the development of new drugs or tailored therapies to treat breast cancer for the next generation of women. Breast cancer is currently one of the major causes of premature death in women.

"BRCA1 women have approximately a 65 percent lifetime chance of developing hereditary 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," the Institute’s Dr. Geoff Linderman said.

Luminal progenitor cells in women with BRCA1 mutations are cells that 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 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," said Linderman, who led the study with colleague Jane Visvader.

Dr. Visvader said in the long-term, breast biopsies might be able to reveal misbehaving luminal progenitor cells. What's more, certain 'markers' might one day help guide diagnosis and treatment.

The National Cancer Institute has more information on BRCA1 gene, its cancer risk and genetic testing.

Azsunshinegirl, aka Lynette Summeriill, is an award-winning journalist who lives in Scottsdale. In addition to writing about cancer-related issues, she writes a blog, Nonsmoking Nation, which follows global tobacco news and events.

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