Potential therapy for postpartum breast cancer investigated

From the Winter 2015 edition of Vanderbilt Medicine Magazine

Nearly 25 percent of all breast cancers among premenopausal women occur within two to five years following a pregnancy.

These postpartum tumors are more likely to spread or metastasize to other parts of the body, leading to an increased risk of death.

A new study led by Rebecca Cook, Ph.D., assistant professor of Cancer Biology, and published in the November 2014 issue of the Journal of Clinical Investigation, helps explain the cellular activity that leads to breast tumor metastasis among women who have recently given birth.

Breast tissues undergo massive transformations during pregnancy in preparation for nursing the new infant. After milk production has ended, there is a cascade of cell death.

“This cell death removes about 90 percent of breast epithelial cells during a very short window of time, which triggers widespread remodeling and repair of breast tissue by the immune system,” explained Cook.

During this remodeling, immune cells operate like tiny Pac-Man arcade game characters, gobbling up the dying cells before they can release intracellular contents which can provoke immune attack. As another safeguard against immune attack, macrophages that ‘eat’ dying cells also secrete immune suppressive factors. Macrophages use one molecule —MerTK— to control both of those processes.

Using a mouse model, Cook and her colleagues found that immune suppression in the postpartum breast triggered by MerTK mistakenly protects tumors, increasing their ability to spread.

The investigators treated mice harboring postpartum tumors with an investigational drug labeled BMS-777607, designed to inhibit MerTK. Following treatment, investigators saw decreased clean-up of dying breast cells in the postpartum breast, decreased immune suppression and decreased metastasis. The drug, which is in clinical testing for other forms of cancer, was used for just seven days to avoid disrupting the immune response and creating autoimmunity.

By Dagny Stuart