Grants Funded

Abstract
Project Summary: People have been concerned for over 40 years about breast implant safety. One area of particular concern has been a postulated link between breast implants and cancer; however, epidemiologic studies have shown this not to be the case. In fact, multiple large-scale studies have shown a reduced incidence of breast cancer in women with cosmetic implants (1-5). The prevailing hypothesis for this finding was that this was simply a selection bias. However, a closer review of the literature suggests that this protective effect persists when controlling for various confounding factors. In fact, meta-analysis demonstrated a rather significant relative risk of 0.62 (95% confidence interval 0.56-0.71) compared to age matched expected frequencies. These findings are supported by a rat model of breast implants that demonstrated a lower incidence of breast cancer development when exposed to breast cancer cells. This lower incidence was not seen in rats with implants located elsewhere (not in the mammary glands), emphasizing a local effect of the implant on reducing breast cancer development (7). Is there any putative biologic mechanism that could explain this finding? We postulate that just as implants have been thought to have potential negative immunologic reactions (heightened autoimmune hypersensitivity, immune progression to ALCL), conversely, could there by immune reactions that are in fact beneficial? Specifically, could heightened immune surveillance induced by the presence of a foreign body breast implant provide collateral immunoprotection against breast cancer? Incipient pilot investigations addressing this question by our team have suggested that indeed there is heightened breast cancer immunosurveillance in women with breast implants manifested by elevated antibodies against specific breast cancer antigens, mammaglobin-A and MUC-1. The next logical step in our discovery pathway is to determine if there is a T cell mediated response. To this end, we propose a series of experiments in which we assay for peripheral blood CD4+ helper T cell activation to breast cancer antigen, local CD4+ helper T cell activation to breast cancer antigen and cytotoxic T cell responses towards breast cancer in women with breast implants compared to implant naïve women. Our central hypothesis is that CD4+ helper T-cells recognize breast cancer antigens to coordinate an immuno-protective response to prevent the development of breast cancer in women with breast implants. Impact Statement: A correlation between breast implant placement and induction or augmentation of T cell responses to breast cancer associated antigens would promote the use of implants not only for psychological benefit, but also for therapeutic benefit. If different local inflammatory responses around the implant are linked to systemic immune responses, this would elucidate a potential therapeutic mechanism that may guide future breast cancer treatment. These findings would lend support to the novel use of breast implants as a vector for vaccine delivery. If no link is found between implants and immune recognition of breast cancer associated antigens, then this suggests the decrease in breast cancer seen epidemiologically in women with breast implants is not mediated by the immune system.

Biography
Dr. John Kim is a Professor of Surgery at Northwestern Feinberg School of Medicine. His clinical and academic research focus is on breast cancer reconstruction. He started his research career as a 3-year Howard Hughes Medical student fellow working under Dr. Victor Dzau at Stanford, examining the effect of decoy oligonucleotides in blocking NFkb inflammatory processes as well as E2F mediated cellular proliferation in various animal models. Upon joining the faculty at Northwestern, he worked with Dr. Thomas Mustoe on projects related to wound healing and scar re-modelling. He then transitioned his research to breast cancer reconstruction as that aligned with his evolving clinical focus. Dr. Megan Fracol is a fifth year resident in plastic and reconstructive surgery at Northwestern Memorial Hospital. Her initial interest in cancer immunology began when she took an immunology course as an undergraduate and was introduced to the concept of harnessing the patient’s own immune system to fight their cancer in the same way it fights disease. She then worked under Dr. Brian Czerniecki at the University of Pennsylvania on a breast cancer vaccine for four years in medical school. Following this, she performed a research year with a grant under Allergan and a Dixon institutional grant to study the effects of breast implants on breast cancer immunosurveillance. She plans to continue to pursue her interest in cancer immunotherapy research.