Skin Electrical Resistance as a Diagnostic and Therapeutic Biomarker of Breast Cancer Measuring Lymphatic Regions

Skin changes associated with alterations in the interstitial matrix and lymph system might provide significant and measurable effects due to the presence of breast cancer. This study aimed to determine if skin electrical resistance changes could serve as a diagnostic and therapeutic biomarker associated with physiological changes in patients with malignant versus benign breast cancer lesions. Forty-eight women (24 with malignant cancer, 23 with benign lesions) were enrolled in this study. Repeated skin resistance measurements were performed within the same session and 1 week after the first measurement in the breast lymphatic region and non-breast lymphathic regions. Intraclass correlation coefficients were calculated to determine the technique’s intrasession and intersession reproducibility. Data were then normalized as a mean of comparing cross-sectional differences between malignant and benign lesions of the breast. Six months longitudinal data from six patients that received therapy were analyzed to detect the effect of therapy. Standard descriptive statistics were used to compare ratiometric differences between groups. Skin resistance data were used to train a machine learning random forest classification algorithm to diagnose breast cancer lesions. Significant differences between malignant and benign breast lesions were obtained (p<0.01), also pre- and post-treatment (p<0.05). The diagnostic algorithm demonstrated the capability to classify breast cancer with an area under the curve of 0.68, sensitivity of 66.3%, specificity of 78.5%, positive predictive value 70.7% and negative predictive value 75.1%. Measurement of skin resistance in patients with breast cancer may serve as a convenient screening tool for breast cancer and evaluation of therapy. Further work is warranted to improve our approach and further investigate the biophysical mechanisms leading to the observed changes.

[1]  C. Begg,et al.  Breast cancer after chest radiation therapy for childhood cancer. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  N. Houssami,et al.  Imaging Surveillance After Primary Breast Cancer Treatment. , 2017, AJR. American journal of roentgenology.

[3]  Benjamin Sanchez,et al.  Functional Mixed-Effects Modeling of Longitudinal Duchenne Muscular Dystrophy Electrical Impedance Myography Data Using State-Space Approach , 2019, IEEE Transactions on Biomedical Engineering.

[4]  Ryan J Halter,et al.  The correlation of in vivo and ex vivo tissue dielectric properties to validate electromagnetic breast imaging: initial clinical experience , 2009, Physiological measurement.

[5]  Susan C. Hagness,et al.  Electromagnetic Spectroscopy of Normal Breast Tissue Specimens Obtained From Reduction Surgeries: Comparison of Optical and Microwave Properties , 2008, IEEE Transactions on Biomedical Engineering.

[6]  Sverre Grimnes,et al.  Comparison between the AC and DC measurement of electrodermal activity. , 2017, Psychophysiology.

[7]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[8]  K. Foster,et al.  Dielectric properties of tissues and biological materials: a critical review. , 1989, Critical reviews in biomedical engineering.

[9]  T Iritani,et al.  Measurement of the electrical bio-impedance of breast tumors. , 1990, European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes.

[10]  A. Liberati,et al.  Follow-up strategies for women treated for early breast cancer. , 2005, The Cochrane database of systematic reviews.

[11]  Zhenyu Guo,et al.  A review of electrical impedance techniques for breast cancer detection. , 2003, Medical engineering & physics.

[12]  Hyo-Eun Kim,et al.  Changes in cancer detection and false-positive recall in mammography using artificial intelligence: a retrospective, multireader study. , 2020, The Lancet. Digital health.

[13]  Eyal Zimlichman,et al.  Diagnosing Diseases by Measurement of Electrical Skin Impedance , 2007, Annals of the New York Academy of Sciences.

[14]  A. Jemal,et al.  Global cancer statistics, 2012 , 2015, CA: a cancer journal for clinicians.

[15]  J. Rosell,et al.  Skin impedance from 1 Hz to 1 MHz , 1988, IEEE Transactions on Biomedical Engineering.

[16]  S. Duffy,et al.  Effect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial , 2020, The Lancet. Oncology.

[17]  Sverre Grimnes,et al.  Sources of error in tetrapolar impedance measurements on biomaterials and other ionic conductors , 2007 .

[18]  B. Brown,et al.  Use of electrical impedance spectroscopy to detect malignant and potentially malignant oral lesions , 2014, International journal of nanomedicine.

[19]  Eugenio Paci,et al.  Overdiagnosis in Mammographic Screening for Breast Cancer in Europe: A Literature Review , 2012, Journal of medical screening.

[20]  Zena Werb,et al.  Roles of the immune system in cancer: from tumor initiation to metastatic progression , 2018, Genes & development.

[21]  Jennifer J. Gibson,et al.  Electromagnetic breast imaging: results of a pilot study in women with abnormal mammograms. , 2007, Radiology.

[22]  A W Partin,et al.  Bioimpedance: Novel use of a minimally invasive technique for cancer localization in the intact prostate , 1999, The Prostate.

[23]  Paul Geladi,et al.  Skin cancer identification using multifrequency electrical impedance-a potential screening tool , 2004, IEEE Transactions on Biomedical Engineering.

[24]  B. Blad,et al.  Impedance spectra of tumour tissue in comparison with normal tissue; a possible clinical application for electrical impedance tomography. , 1996, Physiological measurement.

[25]  Dieter Haemmerich,et al.  In vivo electrical conductivity of hepatic tumours. , 2003, Physiological measurement.

[26]  Sverre Grimnes,et al.  Measuring depth depends on frequency in electrical skin impedance measurements , 1999 .

[27]  Gary H Lyman,et al.  American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  David Gur,et al.  Classification of thyroid nodules using a resonance-frequency-based electrical impedance spectroscopy: a preliminary assessment. , 2013, Thyroid : official journal of the American Thyroid Association.

[29]  Karla Kerlikowske,et al.  Factors Associated With Rates of False-Positive and False-Negative Results From Digital Mammography Screening: An Analysis of Registry Data , 2016, Annals of Internal Medicine.

[30]  L. Robison,et al.  Radiation dose and breast cancer risk in the childhood cancer survivor study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  Hyeuknam Kwon,et al.  Modeling and Reproducibility of Twin Concentric Electrical Impedance Myography , 2021, IEEE Transactions on Biomedical Engineering.

[32]  Christine A Erdmann,et al.  Radiation and breast cancer: a review of current evidence , 2004, Breast Cancer Research.

[33]  D. Kopans,et al.  Cumulative Probability of False-Positive Recall or Biopsy Recommendation After 10 Years of Screening Mammography: A Cohort Study , 2012 .

[34]  Stuchly,et al.  Dielectric properties of breast carcinoma and the surrounding tissues , 1988, IEEE Transactions on Biomedical Engineering.

[35]  J. Jossinet Variability of impedivity in normal and pathological breast tissue , 1996, Medical and Biological Engineering and Computing.

[36]  N. J. Avis,et al.  An in vivo comparative study of the pregnant and nonpregnant cervix using electrical impedance measurements , 2000, BJOG : an international journal of obstetrics and gynaecology.

[37]  Alex A. T. Bui,et al.  Non-Invasive Electrical Impedance Tomography for Multi-Scale Detection of Liver Fat Content , 2018, Theranostics.

[38]  Noriaki Ohuchi,et al.  Age‐specific interval breast cancers in Japan: estimation of the proper sensitivity of screening using a population‐based cancer registry , 2008, Cancer science.

[39]  K. Kerlikowske,et al.  Variability and accuracy in mammographic interpretation using the American College of Radiology Breast Imaging Reporting and Data System. , 1998, Journal of the National Cancer Institute.

[40]  Bruschi,et al.  Classification of , 2010 .

[41]  Wasim Q. Malik,et al.  Separation of Subcutaneous Fat From Muscle in Surface Electrical Impedance Myography Measurements Using Model Component Analysis , 2019, IEEE Transactions on Biomedical Engineering.

[42]  T. Endo,et al.  Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial , 2016, The Lancet.

[43]  A. R. Koomen,et al.  Sensitivity, specificity and predictive values of breast imaging in the detection of cancer. , 1997, British Journal of Cancer.

[44]  Brian L Sprague,et al.  Screening ultrasound as an adjunct to mammography in women with mammographically dense breasts. , 2015, American journal of obstetrics and gynecology.

[45]  G. Ian Taylor,et al.  Annals of Surgical Oncology 15(3):863–871 DOI: 10.1245/s10434-007-9709-9 The Lymphatic Anatomy of the Breast and its Implications for Sentinel Lymph Node Biopsy: A Human Cadaver Study , 2022 .

[46]  Keith D. Paulsen,et al.  Real-Time Electrical Impedance Variations in Women With and Without Breast Cancer , 2015, IEEE Transactions on Medical Imaging.