Understanding the etiology of inflammatory breast cancer

Date
2015
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University of Delaware
Abstract
Inflammatory breast cancer (IBC) is a particularly aggressive form of breast cancer that accounts for at least 1 to 6% of all breast cancer cases in the US and carries a poor prognosis, with a 5 year disease-free survival rate of less than 45%. Clinical features include erythema, edema, peau d'aurange appearance, and skin thickening. It typically does not result in a palpable tumor mass and emboli are often found to have invaded the dermal lymphatic vessels. This invasion is thought to be a driving factor of the rapid onset of metastasis. Understanding the cause of IBC is of utmost importance as little is known about it, yet the possibility of it being infectious dramatically increases the need for research. It has been found that TLR4 is highly overexpressed in IBC compared to nonIBC. TLR4 is activated by Gram-negative bacteria and some viruses. Correspondingly, the occurrence of IBC in clusters as well as seasonally suggests the involvement of an environmental agent. Immunohistochemical staining showed TLR4 was highly expressed in tumor cells as well as the epidermis. The effect of TLR4 expression on the IBC phenotype was then studied by creating a TLR4 knockout IBC cell line. This knockout resulted in a decreased number of viable cells and thus may indicate TLR4 signaling is involved in promoting cell proliferation. In addition, two polymorphisms involved in infectious diseases were also screened for by PCR, neither were found to be common in IBC patients. In fact, the presence of polymorphisms was less than what would be expected and therefore may have a preventative effect. For the detection of an infectious agent, a PCR procedure was developed to prevent false positive results, a common problem with bacterial screening. Bacterial screening of cell lines resulted in inconclusive results due to contamination, however, MMTV screening detected viral DNA in the SUM149 IBC cell line. Isolation of a bacterial agent was also attempted by culturing IBC cells, though no bacterial growth was obtained. However, these methods can be applied to patient samples which will provide more insight in identifying an infectious agent in the development of IBC.
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