Researchers have discovered that certain breast cells are responsible for breast cancers that develop in women carrying mutations in the gene BRCA1. The cells—called luminal progenitor cells—are believed to be the cause of “basal-like” breast cancer, a particularly aggressive form of the disease, according to a study appearing in Natural Medicine. The new finding could open the way to creating new drugs or treatments for women with the cancer, one of the biggest causes of premature death in women.

Earlier, scientists believed breast stem cells caused BRCA1 tumors. However, research has shown that breast tissue from women with BRCA1 mutations has unexpectedly high numbers of luminal progenitor cells, according to Jane Visvader, associate professor of the Walter and Eliza Hall Institute’s Victorian Breast Cancer Research Consortium Laboratory.

The study, using donated breast tissue from women undergoing breast surgery, revealed that BRCA1 breast tissue and basal breast tumors were more similar to normal luminal progenitor cells than any other cell type in the breast, Visvader says. “This places the spotlight on errant luminal progenitors, rather than breast stem cells,” she adds.

Luminal progenitor cells in women with BRCA1 mutations have forgotten how to behave, says Geoff Lindeman, associate professor of the Walter and Eliza Hall Institute’s Victorian Breast Cancer Research Consortium Laboratory.

"Usually, luminal progenitor cells multiply rapidly in the presence of certain growth factors,” says Lindeman, who also heads the Familial Cancer Centre at the Royal Melbourne Hospital. “In BRCA1 women these cells don't even require growth factors to proliferate—they misbehave from the outset.”

The BRCA1 gene is required for normal DNA repair, Lindeman says. “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 notes.

In the future, there may be ways to reveal the misbehaving cells before it turns into breast cancer, an outcome that 65 percent of BRCA1 women face. Visvader says breast biopsies and certain markers might one day help guide diagnosis and treatment.

"For example, c-KIT is a key marker of the luminal progenitor cell and I expect we will see an increase in pathologists routinely using this as a diagnostic marker for basal-like tumors," she says. "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."

The identification of the luminal progenitor cell, along with stem cells and other cell types, is now revealing a breast cancer roadmap that’s  highlighting cancer-prone cell types and key genetic pathways. That will, hopefully, lead to new, tailored therapies for the next generation of women, Lindeman says.