Researchers open door for new ways to treat aggressive form of breast cancer

25 May 2012

Toronto -

Researchers from Toronto and North Carolina, partly funded by the Canadian Cancer Society, have advanced our understanding of an aggressive form of breast cancer called basal-like breast cancer (a type of ductal breast cancer). There are currently no targeted treatments for this sub-type of cancer, which occurs more often in younger women, especially young mothers. Women with basal-like breast cancer tend to have a poor prognosis. The discovery, published on May 25 in the journal Cancer Cell, could ultimately lead to new treatment options.

Breast cancer is the most commonly diagnosed cancer in Canadian women, representing 26% of all newly diagnosed cancer cases. It is a complex disease to treat because each patient’s tumour has a unique genetic profile, and individual tumours respond to therapy in distinct ways. Research over the last few years has significantly increased our understanding of the molecular variations of breast cancer. In the last decade, for example, genomic studies have established five breast cancer subtypes, including basal-like tumours.

Basal-like breast cancer is an aggressive cancer subtype that makes up about 15% of all breast cancers and tends to have a poorer outcome than other types. It tends to strike younger women and also occurs more often in Black women. Currently, there are no known therapies that specifically target basal-like tumours, so these patients are desperately in need of new treatment options.

In the study, which took 10 years to complete, researchers investigated the role of a breast cancer protein called Notch, which helps send signals to cells telling them to divide. Previous studies have shown that Notch is unusually overactive in breast cancer, which encourages cancer cells to grow out of control and spread around the body, which often leads to more lethal outcomes. Understanding Notch could give important clues for new ways to treat breast cancer.

To find out more about Notch’s role in breast cancer, the researchers used genetically-engineered mutant mice to examine a protein called Lunatic Fringe. This protein, when functioning normally, ensures that the cell-division signals sent by Notch are kept in check. But when the researchers disrupted normal functioning of the Lunatic Fringe protein, they found that Notch sent too many growth signals and the mice developed basal-like breast tumours.

The researchers, based at Toronto’s SickKids Hospital, Princess Margaret Hospital and the University of North Carolina, then analyzed Lunatic Fringe levels in samples from 676 breast cancer patients, and were able to confirm the findings in human basal-like tumour samples.

“Results from this study have helped us to identify some features of human basal-like breast tumours that were not previously known,” says Dr Sean Egan of Toronto’s SickKids Hospital, who led the study. “This gives us some exciting new ideas for combining drugs so we can try to inhibit the events that lead to this aggressive cancer.”

“This is a very important study that gives us better insight into the signaling pathways underlying basal-like breast cancer,” says Mary Argent-Katwala, Director of Research, Canadian Cancer Society. “By understanding the roles of the various molecular players, it should be possible to test new combinations of treatments so that women with basal-like breast cancer will live longer, healthier lives.”

The research was supported by the Canadian Cancer Society, Susan G. Komen for the Cure, Genome Canada, the NCI Breast SPORE Program, and the Breast Cancer Research Foundation.


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