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Molecular pathway linked to breast cancer recurrence

September 20, 2005

A study published in the September issue of Cancer Cell provides new evidence for a genetic pathway that is involved in the recurrence of breast cancer and identifies a potential target for development of new anticancer therapeutics. The research makes use of a unique mouse model of breast cancer that provides insight into the molecular and cellular events that lead not only to tumor development, but also to recurrence of the disease. The findings are particularly significant as they are substantiated in human breast cancer samples.

Breast cancer is the most common cancer among women worldwide and is a leading cause of death from cancer in women. In addition, since a number of effective treatments exist for breast cancer, this represents by far the most prevalent cancer in the world, with more than 5 million women currently living with this disease. Although death from breast cancer is most commonly due to recurrence of the disease, little is known about the mechanisms that underlie relapse. Dr. Lewis A. Chodosh from the University of Pennsylvania School of Medicine in Philadelphia led a study using a mouse model of recurrent breast cancer to examine the mechanisms that allow tumors to evade therapy and reappear after a disease-free interval.

The researchers show that recurrent mammary tumors in the mouse model display characteristics of a cellular transition that was previously linked with breast cancer and also exhibit increased levels of the transcriptional repressor, Snail. Snail was sufficient to induce this cellular transition in primary breast cancer cells and to promote mammary tumor recurrence in mice. Further, genetic screening of human breast cancer samples revealed that high levels of Snail expression strongly predicted decreased relapse-free survival in women with breast cancer.

This study reveals one of the first molecular pathways to be causally implicated in mammary tumor recurrence, and suggests that Snail may play a role in the progression of human breast cancers. "While it is not possible to confirm a causal role for Snail in human breast cancer recurrence until drugs are available to inhibit this pathway, we believe that treatment of patients with pharmacologic agents that block Snail expression or function may be a promising approach to preventing breast cancer relapse. Snail may thereby represent an important target for a new generation of cancer therapeutics directed against specific molecules involved in breast cancer recurrence," explains Dr. Chodosh.

Cell Press