Our Stories

Higher death risk for obese breast cancer patients, study finds

A new study found a 34 percent increase in mortality for women diagnosed with the most common type of breast cancer who were obese before menopause. An obese person may have increased levels of insulin, which can help certain cancer cells reproduce. Fat tissue also produces excess estrogen, another breast cancer risk factor. Vinita Nair reports.


Marc Pegram, MD


Pegram is a renowned clinician and scholar of breast cancer research and a leader in translational medicine. As part of the newly opened Women’s Cancer Center Clinic, Pegram will help bring newly developed breast cancer therapeutics to clinical trials, conduct his own research and treat patients.

“Our goal is to improve our ability to extend quality and quantity of life for breast cancer patients,” said Beverly Mitchell, MD, director of Stanford Cancer Institute. “Mark is going to help accomplish this by bringing together excellent clinical care and new approaches to the diagnosis and treatment of breast cancer.”

The funds raised at the Roll Out the Red Carpet Event help underwrite Expedition Inspiration’s Annual Laura Evans Memorial Breast Cancer Symposium, which Pegram has attended several times.

We’re not sure what Pegram has in store for his speech, but if his performance in our Open Forum in March was any indication, we are in for a treat. Dr. Pegram’s background and knowledge are unprecedented, and his ability to deliver complex information in understandable terms makes his reports enjoyable and entertaining.

Marc Lippman, MD

I would like to describe for the Expedition Inspiration community a different approach that we have been taking in our laboratory to understanding breast cancer. The development of overt metastatic breast cancer is overwhelmingly responsible for its lethality. An extraordinary amount of successful research has been undertaken to understand the changes that occur in primary breast epithelium, which allow it to become progressively more invasive and ultimately metastatic.

Considerable research has documented changes in breast cells that allow them to migrate, invade, be transported through the bloodstream and establish growing deposits at distant sites. This is overwhelmingly the most widely pursued area for cancer research–understanding the changes that occur in cancer cells themselves which are responsible for their lethality. While these are very meaningful and useful approaches, we are pursuing a novel and different approach to the cancer process: the ability of breast cancer cells to induce changes in remote normal tissues to make them receptive to metastases.

We believe that a critical component of metastatic disease involves a failure of immune surveillance. We have developed a robust model in which human breast cancers metastasize from the mammary fat pad [the breast] of experimental animals. These breast cancers can secrete a group of cytokines or hormones, which circulate widely and result in the recruitment of a very specific class of immune suppressor cells [myelo-derived suppressor cells, MDSC’s] to tissues throughout the body. We have proven in our model system of human breast cancer in animals that these MDSC’s are essential for the metastatic process.

What is fascinating is that in addition to breast cancer, several other common systemic conditions, including depression and obesity, known to be associated with increased breast cancer incidence and lethality are also associated with high levels of some of the same cytokines.  We have also shown that if we alter the level of these cytokines we can dramatically diminish metastases in our model system. We are now postulating that conditions like depression and obesity are linked in part to cancer risk through the elaboration of similar cytokines which specifically induce local immunosuppression, which augments the metastatic behavior of breast cancer and by treating depression plausibly we may have an impact on breast cancer pathogenesis.

All of this is summarized in the figure. Breast cancer grows as a primary tumor in the breast and then breast cancer cells eventually invade, reach the circulation and spread to other sites. As shown, the primary tumors produce cytokines, which recruit MDSC’s from the bone marrow, which travel in the circulation to many sites. There, we believe, they create an environment which is immunosuppressed and conducive to breast cancer growth. What is quite provocative is the notion that these same cytokines can be produced by alternative non-tumor sources [for example in depression or obesity] explaining how these conditions may encourage breast cancer spread. We have now submitted a grant together with our colleagues at Stanford [one of whom will be joining us at next year’s EI meeting] exploring the value and mechanisms of psychiatric intervention in improving outcomes for breast cancer patients.

We believe that our work has the potential to uncover a critical link between breast cancer metastasis and altered cellular immune functions, which may lead to novel therapeutic interventions aimed at the woman rather than at the cancer itself.