Sylvester Physicians to Investigate Breast Cancer and Depression Connection

Breast cancer patients who suffer from depression may be at an increased risk for metastasis. That connection, however, may provide a target for a novel therapy benefitting thousands of women. Armed with a $200,000 grant from the Florida Breast Cancer Foundation, Marc E. Lippman, M.D., Kathleen and Stanley Glaser Professor of Medicine at the University of Miami Miller School of Medicine, and several colleagues have started new research to more closely examine how depression plays a role in this process in a study, “Depression and Breast Cancer: An Inflammatory Connection?”

While localized breast cancer is curable, physicians continue to search for improved methods to conquer metastatic breast cancer, which is overwhelmingly lethal. Scientists have been working to understand what occurs in normal breast cells that incites them to grow abnormally, invade the bloodstream and move to other organs (metastasize).

“A lot of research has appropriately focused on changes within the breast cells,” said Lippman, who is Deputy Director of the Sylvester Comprehensive Cancer Center and a member of the Braman Family Breast Cancer Institute. “In this study, we are looking at factors within the host, the patient, which promote metastasis.”

In prior studies, Lippman and his team have shown that breast cancer cells have the ability to induce changes in other organs, such as the liver or lungs, so they can serve as metastasis sites. Other studies have shown that many breast cancers can secrete factors called cytokines that circulate widely, recruiting a very specific class of immune suppressor cells to other tissues throughout the body that ultimately support tumor growth and metastasis.

Preliminary data suggest that systemic inflammation may contribute to the aggressiveness of breast cancer progression. A higher breast cancer rate of recurrence and relapse has been shown in women who are depressed, and depression is a disease known to be associated with systemic inflammation and high levels of some of the same inflammatory molecules produced by breast cancers. This strongly suggests that a depressive state may promote the metastatic spread of breast cancer by influencing the immune system. “We want to better understand how systemic inflammation impacts metastatic disease and, ultimately, how we can use that information in a clinical setting,” said Lippman. “We believe it can have a pivotal role and be a potential therapeutic target.”

The two-year grant, which supports Momentum2: The Breakthrough Campaign for the University of Miami, will allow Lippman and his team to identify the biological link between depression and breast cancer progression by analyzing inflammatory molecules in mouse models of breast cancer. The researchers will determine if advanced disease leads to depressive behavior and whether depression accelerates the development of breast cancer. They theorize that either by treating the depressive condition directly or interrupting the cytokine communications associated with it, there could be a beneficial therapeutic effect on metastatic spread and prognosis.

Lippman said, “We believe that our work has the potential to uncover a critical link between breast cancer metastasis and depression which may lead to novel therapeutic interventions, providing better care for breast cancer patients.”

Lippman is also preparing to begin a clinical study comparing the levels of inflammatory molecules, immune suppressor cells and circulating tumor cells in patients at different disease stages. In addition, they will conduct a clinical study in which — for the first time — the impact of anti-depressant therapy on levels of those inflammatory mediators will be quantified in breast cancer patients.

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