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 a-keratin. The feature appeared as a ring with a molecular spacing determined to be 4.76 6 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. ' 2007 Wiley-Liss, Inc.Key words: X-ray diffraction; hair; breast cancer; synchrotron In 1999 James et al. reported differences in the X-ray diffraction patterns of hair from individuals with breast cancer compared to healthy subjects.1 The X-ray diffraction patterns of hair from cancer patients contained a ring of comparatively low intensity, which was superimposed on the normal a-keratin pattern obtained from healthy control subjects and which corresponded to a molecular spacing of d 5 4.44 nm. This ring was reportedly observed in all samples of scalp and/or pubic hair taken from women diagnosed with breast cancer, as well as from subjects ''not yet diagnosed with breast cancer but suspected of being at risk''. In other words, a number of false positives were identified. Subsequent papers by James and coworkers reported X-ray diffraction analysis results of blinded human samples, which were consistent with the initial publication.2,3 The later paper reported on the results of 503 blinded hair sample analyses and demonstrated a sensitivity of 100% (no false negatives) and a specificity of 86% (14% false positives by comparison to mammography) for breast cancer.However, the finding remained highly controversial as several groups independent of James attempted to replicate the original findings and all were unsuccessful. [4][5][6][7][8][9][10][11] The technical explanations for these replication failures [12][13][14][15][16] provide insight into the experimental challenges. Myer et al., 9 whose diffraction data was not of sufficient quality to demonstrate a correlation between an altered X-ray diffraction pattern and the presence of breast cancer, sent the 27 samples they had examined to James who subsequently performed X-ray diffraction a...
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.Key words: breast cancer; X-ray diffraction; hairThe report in 1999 1 suggesting that breast cancer could be diagnosed by X-ray diffraction of hair created enormous interest and skepticism. Several groups attempted to repeat this work and some reported that they were unsuccessful. Their failures highlighted the specialized nature of the technique and their lack of expertise in the fiber diffraction of ␣-keratin in hair. This investigation requires not only expert sample-handling skills but also a very clean and finely focused X-ray beam that has a large signalto-noise ratio combined with a suitable detector system having an extremely wide dynamic range. Several of the research groups 2-6 failed to produce any reflections characteristic of the basic ␣-keratin pattern despite the fact that a normal pattern (Fig. 1a) had been published. 1,7 Figure 1 is a composite image with a normal diffraction pattern on the left-hand side and a pattern with the breast cancer ring on the right-hand side. The 7th and 19th orders of the 47 nm lattice are indicated and clearly visible in both patterns; the diffuse ring associated with breast cancer is also indicated but, as can be seen, is much less intense than the 7th order. Without being able to produce a normal pattern that has the 7th order visible, there is no hope of distinguishing any changes, let alone the ring associated with breast cancer.None of those who failed to reproduce our results followed our protocol. Briki et al. 8 actually reported differences between the normal samples and those from persons with breast cancer, but their methods and results were different from ours. The main difference they reported was the presence of very wide dark rings in their normal samples. A statement by V. James published as a postscript to their paper and demonstrated in a subsequent paper 9 describes these dark rings as artifacts of their sample preparation since these rings were far more intense than the 7th and 19th orders of the 47 nm lattice. They presented samples to the beam by pulling hairs into capillary tubes, which left them loose at the ends, resulting in twisted and unaligned hair shafts. 9 The most recent unsuccessful team 10 used an unsatisfactory method for data analysis that showed their lack of expertise in fiber diffraction and lack of understanding of the normal ␣-keratin pattern. The problems associated with their analys...
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.
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