New Diagnostic Techniques for Breast Cancer Detection

Diagnostic Techniques Under Investigation

The following is not an exhaustive list of all techniques under investigation, but rather is the authors' view on some interesting and promising, and very exciting, new technologies, which may change the way we diagnose breast lesions over the coming decade.

This technique is based on the hypothesis that in vivo breast MR elastographic techniques can quantitatively depict the elastic properties of breast tissue and reveal high sheer elasticity in known tumors.^[69] Based on the differential elasticity of malignant and benign breast tissue, an acoustic wave is applied to breast tissue during MRI and the resultant tissue shifts are imaged using motion-sensitive phase contrast. Analysis of 39 malignant and 29 benign breast lesions resulted in a 20% increase in specificity at 100% sensitivity.^[70] This technique needs further validation and indications for its use need to be outlined by further studies.

Mammary ductoscopy is a diagnostic technique that uses a small-caliber endoscope to visualize ducts and biopsy the mammary ductal epithelium. The ductal lavage fluid also provides cells for cytology. These procedures are under investigation for detection of breast cancer and risk assessment in high-risk populations,^[71] and may be of some use in the investigation of nipple discharge, which is the presenting feature in 5% of symptomatic breast cancer patients.^[72] It is likely to be more accurate than ductography.^[73] Matsunaga et al. described intraductal breast biopsy under direct vision, which may prove a valuable tool for diagnosing and treating intraductal benign breast lesions.^[74] Ductoscopic vacuum-assisted biopsy is a novel technique for breast biopsy under direct vision (Figure 5A & B).^[75]

(Enlarge Image)

Ductoscopy and ductal lavage in the case of nipple discharge. (A) The discharging duct is identified by pressing the nipple. The duct is then cannulated and lavage fluid introduced in the duct and drawn back. (B) View of duct via ductoscopy.

The limitations of mammary ductoscopy are that only a few ducts can be cannulated, and it is difficult to reach terminal and peripheral ducts owing to their narrow caliber.

Optical coherence tomography is an emerging medical imaging modality that offers new capabilities in anatomical and functional imaging in vivo. It visualizes anatomical microstructures in vivo and in real time, with resolutions in the range of 1-10 µm. This is a much finer scale than is possible with ultrasound.^[76] Current work in Western Australia is looking at its utility in defining surgical margins, identifying malignancy in sentinel nodes and ensuring biopsy needles are placed accurately in lesions.

Vibrational spectroscopy measures the energy spectrum of the vibrational mode of tissue molecules using Raman scattering or Fourier transform near-infrared spectroscopy. Shafer-Peltier et al.studied near-infrared Raman spectroscopy in human breast tissues and compared it with hematoxilin-and-eosin-stained images.^[77] They obtained spectra to develop chemical and morphological descriptions to fit normal and diseased breast tissue.

Another study reported discrimination with 100% accuracy between benign and malignant breast tissue using Fourier transform infrared spectroscopy.^[78] Yet another study further categorized spectral differences observed among benign and malignant breast tissue.^[79]

Light-scattering spectroscopy studies specific spectral regions and optical properties of scattering elements in tissues arising from changes in direction of light propagation. Wallon et al. measured near-infrared spectra in breast cancer specimens and found four different spectral regions in cancer tissues.^[80] Another study also observed changes in absorption spectra of different breast conditions.^[81]

Molecular imaging targets specific tumor receptors with fluorescent dyes that are activated by tumor-associated enzymes; this may be used to identify malignant cells in vivo.^[82]

Analysis of volatile organic compounds (VOC) in breath is under investigation to try to establish its place as an adjunct to screening mammography, perhaps allowing identification of women who are unlikely to have a malignancy. These VOC are markers of the oxidative stress associated with breast cancer.^[83] This oxidative stress leads to lipid peroxidation in cell membranes, which generates a variety of alkanes that can be detected in the breath.^[84] Phillips et al. carried out a pilot study of the sensitivity and specificity of a VOC breath test as a marker of disease in women with breast cancer.^[85] They found that the NPV of the breath test was slightly superior to screening mammography (99.93 vs 99.89%).^[85] The main limitation of this study was the small number of subjects; concomitant infectious or inflammatory conditions in the body could potentially skew the results, as these conditions could be the source of oxidative stress. Current work is underway to validate this pilot study.

When human hair is subjected to x-rays it produces a specific scattering or diffraction pattern based on its keratin structure. The molecular structure and packing of intermediate filaments in the hair cortex is reflected in the x-ray diffraction, which can vary in different disease conditions.^[86] Monochromatic synchrotron radiation can provide a high-quality fiber-diffraction pattern, which helps in determining the substructure of intermediate filaments in the hair cortex.^[87,88] Any addition or deletion to the intermediate filament produces a change in the fiber-diffraction pattern. Specific changes have been recorded and confirmed for the hair in breast cancer patients.^[89] James et al. studied hair samples for diffraction in both women with breast cancer and women with an inherited predisposition, and found specific changes in the diffraction pattern in both groups.^[90] The test gave a sensitivity of 100% and specificity of 92%.^[88] This has not been confirmed in other studies,^[91] so further clinical research is required. Out of a total of 856 double-blinded studies to identify the diffraction pattern in breast cancer, 214 fiber-diffraction patterns have correlated with breast cancer cases that were proven positive by surgery or mammogram.^[91] Any physical, chemical or radiological damage to the hair can significantly alter the structure of hair over a period of time, so for the study purpose hairs close to the scalp should be harvested (less than 3 mm from the skin).^[90,91] Care needs to be taken while handling specimens, as stretching, twisting or scraping a hair specimen can alter the diffraction pattern. Most acquired mechanical or chemical damage to the hair manifests as pseudo cancer rings.^[90]

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