Preoperative AUS-FNAC avoided unnecessary SNB in 28.5 per cent of node-positive patients and in 7.8 per cent of patients overall.

BackgroundAcquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR) MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype.MethodsCD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression) or MCF7 cells (± transfection with the CD44 gene) were treated with the CD44 ligand, hyaluronon (HA), or heregulin and their in vitro growth (MTT), migration (Boyden chamber and wound healing) and invasion (Matrigel transwell migration) determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA.ResultsTamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2 and EGFR and induction of cell migration. Overexpression of CD44 in MCF7 cells, which lack endogenous CD44, generated an HA-sensitive phenotype, with HA-stimulation promoting erbB/EGFR activation and migration.ConclusionsThese data suggest an important role for CD44 in the context of tamoxifen-resistance where it may augment cellular response to erbB ligands and HA, factors that are reported to be present within the tumour microenvironment in vivo. Thus CD44 may present an important determinant of breast cancer progression in the setting of endocrine resistance.

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Background: Minimally-invasive microwave ablation techniques for the management of breast diseases are an emerging technology. These techniques rely, to a certain extent, on the difference in dielectric properties of normal and malignant human tissue. In our unit, we are currently studying the efficacy of a new microwave based technology, MicroBlate®, which has the unique feature of being able to measure tissue impedance and deliver microwave frequency impulse to tissues based on this impedance feedback. In this study we have compared the dielectric properties of normal and malignant breast tissues using this probe to establish proof of principle.Methodology:Impedance of freshly excised mastectomy and reduction specimens were measured ex-vivo using the MicroBlate® probe. This probe was attached to the end of the precision open-ended co-axial cable connected to an Agilent 4-port PNA-L Microwave network analyser (10MHz – 20 GHz). Impedance (Z) was intially recorded as two values which are vector quantities: real (R), which reflects the tissue resistance, and imaginary (X), a measure of tissue reactance. The overall impedance was then calculated using the standard mathematical formula, Z= √(R2+X2). Measurements were performed on adipose, glandular and malignant breast tissue immediately following surgical excision. Differences in the impedance values between these tissue types were calculated and the results analysed using appropriate statistical tests.Results:Our study shows a measurable difference in the dielectric properties of malignant and normal breast tissue. Our data supports the technological basis of MicroBlate®, a minimally invasive microwave ablation technology with impedance feedback, further ex-vivo studies are needed to determine its efficacy in ablating benign and malignant breast tissue. 28 patients undergoing elective mastectomy (n=26) and reduction (n=2) were included in this study between Feb – May 2009. Of the 26 patients undergoing mastectomy, 19 had invasive malignancy and the remaining 7 had in-situ malignancy only. The median age of the patients was 58 years (range 22-80 years). The average impedance of adipose tissue was 29.3 ± 6.9W, glandular tissue was 31.1 ± 6.1W and for malignant tissue was 49.6 ± 9.3W (Mann Whitney U p value <0.001). The average difference between impedance of malignant and glandular tissue in individual patients was 19.6 ± 8.6W.Conclusions:Our study shows a measurable difference in the dielectric properties of malignant and normal breast tissue. Our data supports the technological basis of MicroBlate®, a minimally invasive microwave ablation technology with impedance feedback, further ex-vivo studies are needed to determine its efficacy in ablating benign and malignant breast tissue. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3099.

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