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2008 Annual Meeting Abstracts

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A Novel Biomarker for the Detection of Recurrent or Occult Breast Cancer in a Previously Reconstructed Breast with Silicone Implants
Raj S. Ambay, MD, DDS, Richard B. Halberg, PhD, Joseph Grudzinski, MS, Catherine G. Gard, MS, Scott B. Reeder, MD, PhD, Karol A. Gutowski, MD, Jamey P. Weichert, PhD.
University of Wisconsin, Madison, WI, USA.

PURPOSE: After a 14-year moratorium, the FDA recently approved the use of silicone breast implants in the United States. Their natural feel and contour have lead to an increase in demand and placement in women with a history of breast cancer. In this select subset of patients, the surveillance for recurrent or occult cancer following reconstruction with silicone breast implants is of paramount importance. Studies have shown that Eklund mammographic displacement views fail to view between 10-30 percent of breast tissue and MRI has a high false-positive rate which may prompt unnecessary removal of the implant. To circumvent these issues and further increase the safety profile of silicone breast implants, a novel tumor-specific synthetic biomarker, NM404 was developed. The primary aim of this study was to evaluate the ability of radioiodinated NM404 to accurately detect recurrent or occult breast cancer in patients with silicone breast implants. This study may eliminate obscurity of breast tissue caused by silicone implants and prevent unnecessary removal of implants due to false-positives by MRI.
METHODS: BalbC mice (n=15), were implanted with 4mm cubes of silicone breast implants. The cubes were taken from recently approved FDA breast implants manufactured by Allegan and by Mentor. The 4mm cube contained a sample of the implant shell and on the other five sides, the exposed cohesive silicone gel. 4T1 human breast cancer cells were xenografted into the chest wall and flanks of all mice. Negative controls included mice implanted with a 4mm cube of the breast implant and no tumor, and positive controls consisted of mice with mammary tumor xenografts, without the silicone implant. Animals were administered 18F-FDG and 124I-NM404 then imaged by dual-modality microPET/microCT and compared to scans done by MRI. Tumors were quantified in-vivo, explanted, and histologic correlation was performed.
RESULTS: Radioiodinated NM404 visualized with microPET/microCT reliably detected occult mammary tumor in all 15 xenografted mice implanted with either Allergan or Mentor implants, even in the MRI negative images. Mathematical quantification was used to confirm the visual existence of breast tumor and decipher its distinct margins. 18F-FDG, the current gold standard for cancer biomarkers was compared to 124I-NM404 in the setting of inflammation created from exposed silicone, surgical placement and inflammation from the tumor. NM404 demonstrated clear visualization of the tumor, while FDG demonstrated inconsistent visualization. NM404 was retained within the tumor for twelve days implying the possibility of tumor targeted radiotherapy rather than large field therapy which may limit the options for breast reconstruction. There were no significant differences (p<0.05) between the imaging characteristics of tumor-bearing animals with or without silicone implants.
CONCLUSION: Our results indicate that NM404 using dual-modality imaging, is more accurate than MRI in detecting occult and recurrent breast cancer in patients with silicone breast implants. Furthermore, NM404 is tumor-specific. The use of this biomarker may obviate the concerns of patients, oncologists and radiologists regarding obscurity of breast tissue in patients with silicone breast implants. Finally, its potential use as a delivery vehicle for radiation may preserve surrounding breast tissue for reconstruction.


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