This is the third in a series of blog posts written by UVM College of Medicine 2016 Summer Research Fellows.
I have always been particularly interested in breast cancer because of my family history: my grandmother was a survivor of breast cancer, and my aunt is doing well after her diagnosis and double mastectomy last year. My grandmother and aunt were both incredibly strong throughout their diagnosis, surgery, and recovery, and were both pronounced cancer free. Unfortunately, not all women are that lucky. About one in eight women will develop invasive breast cancer over the course of her lifetime and in spite of many of the advances in screening procedures, prevention, and therapy, breast cancer is still the second leading cause of cancer death in women.
I was very excited when I heard about the research being done by Dr. Ted James and Dr. Mercedes Rincon to investigate the inflammatory process within breast cancer tissue that is induced by core needle biopsies or other surgical interventions. After a mammogram is performed and a suspicious area is identified, the standard diagnostic procedure is a core needle biopsy. The sample of tissue from the biopsy is sent to pathology and evaluated for the presence of breast cancer. Once the diagnosis of breast cancer is made, a surgery is scheduled for the excision of the tumor. Recent studies have shown that the core needle biopsy causes a local, acute inflammatory reaction in the breast cancer tissue. The recruitment of inflammatory cells and their secretion of cytokines changes the microenvironment of the cancer cells and can have an impact in the tumor and influence the proliferation of tumors cells and the risk of metastasis. Furthermore, it has been hypothesized that if a patient with breast cancer undergoes surgery and not all of the cancer is removed, then the inflammatory reaction caused by the surgery may increase the risk of residual tumor cells dividing and metastasizing to other areas of the body before a re-excision is able to be performed. This research suggests that standard diagnostic and therapeutic interventional procedures, including core needle biopsies and surgical excision of the tumor, may aid in tumor progression and/or metastasis by triggering the acute inflammatory response. Our goal is to identify anti-inflammatory drugs that decrease the inflammation within the tumor and combine them with surgical interventions to better treat breast cancer.
This summer, I have been investigating the role of interleukin-6 (IL-6), a cytokine secreted by inflammatory cells, in the acute inflammatory reaction that is induced by a biopsy. I am staining human breast cancer tissue and looking for the presence of IL-6 positive cells proximal and distal to the biopsy site. If the cytokine IL-6 is being released by inflammatory cells and contributing to the increase in proliferation and metastasis, then treatment with a drug that specifically targets and blocks the IL-6 receptor may reduce the risk of metastasis. I have also been comparing the proliferation of cancer cells and inflammation in tissue from the primary excision and from the re-excision of breast cancer. It is important to characterize the inflammatory reaction in order to determine if there are existing anti-inflammatory treatments that could be used to decrease the proliferation and metastasis induced by iatrogenic intervention. Animal model studies have shown that treatment with a systemic anti-inflammatory, ibuprofen, prior to and after the biopsy reduced the development of metastasis triggered by a biopsy. We are also assessing whether systemic anti-inflammatory treatment attenuates the local immune response triggered by the biopsy within the tumor.
Through my summer research project, I have gained an appreciation for clinical research and the time and patience that goes into furthering our understanding of a particular disease state. The more we know about the pathophysiology of breast cancer, the more likely we are to utilize pre-existing drug therapies or develop a novel targeted therapy that can better treat patients and decrease the morbidity and mortality rate associated with metastasis of breast cancer.