Characterization of a Test for Invasive Breast Cancer Using X-ray Diffraction of Hair-Results of a Clinical Trial.

OBJECTIVE: To assess the performance of a test for breast cancer utilizing synchrotron x-ray diffraction analysis of scalp hair from women undergoing diagnostic radiology assessment. DESIGN AND SETTING: A double-blinded clinical trial of women who attended diagnostic radiology clinics in Australia. PATIENTS: 1796 women referred for diagnostic radiology, with no previous history of cancer. MAIN OUTCOME MEASURES: Sensitivity, specificity and accuracy of the hair test analysis compared to the gold standard of imaging followed by biopsy where indicated. RESULTS: The hair-based assay had an overall accuracy of >77% and a negative predictive value of 99%. For all women, the sensitivity of both mammography and X-ray diffraction alone was 64%, but when used together the sensitivity rose to 86%. The sensitivity of the hair test for women under the age of 70 was 74%. CONCLUSION: In this large population trial the association between the presence of breast cancer and an altered hair fibre X-ray diffraction pattern previously reported has been confirmed. It appears that mammography and X-ray diffraction of hair detect different populations of breast cancers, and are synergistic when used together.

New insights into the nature of the wool fibre surface.

Wool fibres have been treated to remove the covalently bound lipid and characterised using lipid analysis, wettability and scanning probe microscopy. A model substrate consisting of alternating stripes of hydrophobic (predominantly CH(3) terminated molecules) and hydrophilic (COOH terminated molecules) surfaces, micro-printed onto a gold-coated mica surface was assessed using the SPM techniques of adhesion, friction and phase imaging and showed that SPM can easily distinguish these surfaces. When KOH/methanol treated wool fibres were examined, SPM showed an increase in coefficient of friction and a decrease in adhesion as the lipid is removed. The increased friction is consistent with studies on the model surface and confirms the hypothesis that the lipid layer decreases the surface friction of fibres. The decreased adhesion is consistent with results in the literature on hair, but is at odds with the results on the model surface. The strong contrast shown between the methyl and carboxylic acid surfaces in the friction image of the micro-patterned surface, and the complete absence of any such contrast developing with time of treatment of the wool fibres strongly suggests that the surface lipid is not present as a discrete outer layer on the fibre. A new model is proposed in which the lipid is intimately associated with the surface proteins and allows for changes in lipid concentration at the surface in response to changes in environmental conditions.

Diagnosis of breast cancer by X-ray diffraction of hair.

This article presents the results of analyses of hair fibers from women with breast cancer using synchrotron-derived X-ray diffraction. These diffraction patterns contained a new feature superimposed on the normal diffraction pattern of alpha-keratin. The feature appeared as a ring with a molecular spacing determined to be 4.76 +/- 0.07 nm. This feature was not present in the diffraction patterns of hair from women without breast cancer as assessed by other routine clinical diagnostic techniques. Furthermore, different hairs from the same subject analysed on two different synchrotron beamlines give remarkably consistent diffraction patterns. Previous studies by other investigators have suggested that analysis of X-ray diffraction patterns of hair can reveal the presence of breast cancer in clinical and preclinical trials. This finding, however, has not been independently confirmed. The methodologies of sample handling, sample exposure and image analysis are known to be vital. We discuss some of these issues and provide a detailed description of the methodology employed for the sample handling and image analysis and new methodologies developed from this work. We conclude that X-ray diffraction of hair has the potential to provide a non-invasive test for the presence of breast cancer.

Early diagnosis of breast cancer by hair diffraction.

A correlation between the incidence of breast cancer and an observed change in the X-ray diffraction pattern of hair from the afflicted individuals was first reported in 1999. Since that time, over 500 hair samples have been analyzed in double-blinded breast cancer studies with no false negatives being detected. To correlate this observed change with the presence of breast cancer, we examined whiskers removed from nude mice prior to and 8 weeks after subcutaneous implantation of a human breast cancer cell line. Here we show that the change observed in human hair was also evident in whiskers and that it appeared soon after cancer cell implantation.