Jennifer McCormickPathogenesis of Radiation-Induced Capsular ContractureJoan LipaUniversity of TorontoBreast (Cosmetic/Reconstructive)2006CanadaBasic Research Grant

It is estimated that 1 in 7 women in the United States will develop breast cancer, and 270,000 women will be diagnosed in 2005. As a result of earlier detection and improved treatments - surgery, hormonal therapies, chemotherapy, and radiotherapy - the mortality rate for breast cancer patients is at its lowest since the 1950s. This means that more breast cancer patients will survive and live with the sequelae of their treatment.

Post-mastectomy breast reconstruction restores body image and psychological well-being and is recognized as an integral part of breast cancer survivorship. However, complications with resultant poor outcomes occur with tissue expander and implant breast reconstruction in patients requiring radiotherapy - and the indications for adjuvant radiotherapy are increasing. The main complication is fibroproliferation of the capsular tissue around the expander with resultant capsular contracture. This leads to poor expansion, breast distortion with poor aesthetic outcome and pain, and often requires additional surgery. Understanding the pathogenesis of radiotherapy induced capsular fibroproliferation and contracture will allow us to design pharmacological intervention against the development of capsular contracture in patients requiring radiotherapy who may be limited in their options for breast reconstruction.

Recently, experimental evidence is accumulating to indicate that the canonical Wnt (Wingless) signaling pathway plays a pivotal role in the pathogenesis of fibromatosis and hyperplastic skin wounds. It is most likely that intervention at the mediator or effector level in this signal transduction pathway will attenuate fibroproliferation. Therefore, the purpose of this research project is to test our hyporthesis that the Wnt signaling pathway also plays a central role in the regulation of radiotherapy-induced fibroproliferation in capsular tissue around tissue expanders in postmastecotmy breast reconstruction. To this end, experiments are designed to study the phosphorylation states and protein and/or gene expression of biochemical components known to be involved in the Wnt signaling pathway, and the collagen I and III protein expression in capsular tissue around tissue expanders in patients with or without radiotherapy prior to mastectomy.

 

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