New research is revealing breast cancer's deadly secrets, focusing on how the disease starts and later spreads. One study published yesterday in the journal Nature has identified a pivotal event before breast cancer first buds. Thea Tlsty of the University of California at San Francisco and her colleagues ran cell culture studies of breast epithelial cells. The work revealed that those cells, more often than other cell types, slip past a built-in regulatory control on cell growth called senescence. And when they do escape senescence, the epithelial cells almost always develop genetic changes associated with the very beginnings of breast cancer.

The team was further able to identify molecular markers that indicate when breast epithelial cells have escaped senescence, and how far they have progressed in accumulating damaging genetic changes. Eventually these markers could be used to target cells for cancer prevention and therapy early on. "Figuring out why mutations occurnever mind what they actually arecould provide a new means for intercepting the disease before it gets started," Tlsty says.

A second study from scientists at Massachusetts General Hospital appears in this month's Nature Medicine and reveals a remarkable mechanism by which breast cancer spreads to the lymph nodes and lungs. Researchers long thought that the cancer reaches the lymph nodes via the lymphatic system, but exactly how the cancer got from the tumor to the lymphatic system remained unknown. The new work suggests that tumors actually develop their own internal lymphatic systems. That system then hooks up with the surrounding lymphatic vessels, providing a highway of sorts by which the tumor cells can metastasize. Important to the highway building is a protein known as VEGF-C, which encourages lymphatic vessel growth. "This could provide a new target for therapy," principal investigator Michael Detmar remarks. "By blocking the interaction of VEGF-C with its receptor on the lymphatic system we may be able to block metastasis from occurring."