Background: Breast cancer patients with similar tumor characteristics (size, histological grade, receptor expression, etc.) may have vastly different responses to therapy and clinical outcome with recurrence or not. Recent research indicates that the immune system may play a significant role in how patients respond to cancer. However, how immune cells interact with tumor cells remains poorly understood.

Objective/Hypothesis: We hope to uncover opportunities for novel therapies harnessing the immune response against breast cancer by comprehensively studying the dynamics between breast cancer and the immune system. We seek strategies that will specifically change the interactions between tumor and immune cells and block the immune system dysfunction that cancer cells can cause. With our studies of breast cancer, we hope to design: (a) new diagnostic tools for early detection of breast cancer and surveillance for relapse by looking at the immune system as an indicator of cancer presence in the body; (b) new methods to predict which breast cancer patients will have favorable or unfavorable outcomes, for guiding therapy; and (c) new treatment strategies for breast cancer by harnessing the patient's immune system, particularly the interactions between the tumor cells and immune cells in the lymph nodes nearest to the location of a breast tumor, known as tumor-draining lymph nodes.

Specific Aims: We seek to understand the complex interactions between the immune system and tumor cells in breast cancer. We hope to be able to generate a type of "immune profile" that could be used as a completely new way to accurately predict cancer metastasis and survival of breast cancer patients. Furthermore, we are also going to investigate what is happening to the immune cells on the cellular and molecular levels in hopes of learning more about the mechanisms by which the immune system malfunction occurs that allows cancer cells to grow.

Study Design: In both primary and recurrent tumors, we will use biological and genetic techniques to study cancer cells and immune cells that exist within a tumor or tumor-draining lymph node. We can then compare this information to the clinical data we have about the patients from which the samples were taken. In addition, we will make use of imaging technology and advanced mathematical analyses to examine whether there is something about the spatial relationship between the immune cells and tumor cells in the lymph node that indicates how a cancer will progress. We will combine all of our data to construct a computer model of what is occurring. We can then see how well our model predicts actual patient outcomes and use the model to quickly simulate new therapeutic strategies for breast cancer.

Potential Outcomes and Benefits of the Research: We hope that by examining all of these sets of cells, we can begin to understand how breast cancer cells change as they migrate from the tumor site to the lymph node. We also hope to learn what tumor cell characteristics may precede their migration into the lymph node, what immune changes arise in response to tumor cell invasion, and how these situations may differ between primary and recurrent disease. This work may lead to novel diagnostic tools to help predict clinical outcome and guide therapy in breast cancer patients. Any new insight into the mechanisms of immune evasion by breast cancer cells could ultimately lead to new treatment strategies for breast cancer directed specifically at altering the biology of tumor-draining lymph nodes.