Sub-epithelial impedance: a new non-invasive method to measure mammographic density.
Authors: Greene T , Brumfield MK , Pierce M , Davies RJ 
Published: December 2010

Abstract
Abstract #4075
Background: Breast density is possibly the strongest risk factor for breast cancer after genetic predisposition. Estimation of mammographic density can be highly subjective. More accurate volumetric approaches to measure density using mammography are under development, but require x-ray exposure. Dense breast stroma has a lower electrical resistance, which becomes increased as the stroma is replaced with fat. We have previously reported that the impedance of breast stroma correlates with age, obesity and inversely with position in menstrual cycle. It is unknown whether mammographic density also correlates with stromal impedance. When a high frequency sine wave is used to interrogate the breast the impedance of the overlying skin and the breast epithelium are significantly reduced with most of the remaining impedance being due to the stromal tissue and is defined as the sub-epithelial impedance (Zsub).&#x2028; Patients and Methods: With IRB and patient consent, electrical contact with ductal epithelium was established non-invasively, using a specially designed nipple sensor in 288 women. Measurements were made between the nipple sensor and skin surface electrodes placed in each of 4 quadrants of the breast. Zsub was measured at 60 KHz using a frequency response analyzer, and sine-wave correlation technique. Data were analyzed using a t-test, Mann-Whitney test, ANOVA, Pearson Moment Correlation, and stepwise regression as appropriate. In a subset of 112 women, in whom mammograms were available, a blinded review was performed to estimate the percent density averaged for two views of each breast.&#x2028; Results: Zsub correlated with age of the patients (n = 288), (0.58 Correlation Coefficient (CC), p &lt; 0.0001). Zsub was elevated in women who underwent a biopsy demonstrating breast cancer (n = 52) or proliferative breast disease (n = 27) with values of 211 ± 19Ω (median ± SEM), and 216 ± 18Ω respectively, compared with women with benign biopsies (n = 75) and values of 131 ± 15Ω (p &lt; 0.01). In a subset of patients (n=112) Zsub was inversely correlated with mammographic density (-0.68 CC, p &lt; 0.0001). Body mass index (BMI) increased with age (0.20 CC, p &lt; 0.05), Zsub (0.48 CC, p &lt; 0.00001) and inversely with mammographic density (-0.51 CC, p &lt; 0.0001). Using stepwise regression, mammographic density was predicted by a linear combination of age, BMI and Zsub with a coefficient of 150.22 ± 11.98 (SE), Age -0.64 ± 0.20 (p &lt; 0.002), BMI -1.43 ± 0.42 (p &lt; 0.001) and Zsub -0.21 ± 0.04 (p &lt; 0.001).&#x2028; Discussion: Mammographic breast density decreases with increasing age and BMI because of replacement of stromal tissue with fat, which likely also affects the sub-epithelial electrical impedance of the breast. Breast density can be estimated non-invasively and objectively using measurements of Zsub. Increased impedance of the breast parenchyma may represent a novel biomarker of breast cancer risk associated with mammographic breast density.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4075.