Breast Cancer

Degradation and penetration of the extracellular matrix (ECM) within breast tissues are major processes in the progression of cancer. It is well known that the structure of ECM components is seriously disturbed in malignant breast lesions and that the ECM is largely collagen.

Part of our work, which is directed by the Enhanced Breast Imaging Group, is to identify any changes to collagen supramolecular structures associated with breast tumours. These structures are measured using small angle X-ray diffraction (SAXS) and synchrotron radiation.

Our specimens are 'core cut' biopsy tissues provided both directly from patients and excised from reduction mammoplasty samples. Radial integration of the 2-dimensional diffraction data acquired from these experiments has enabled us to examine Bragg reflections and Bessel function peaks simultaneously.

We have found that, although both tumour and normal breast tissue collagens are of similar type (type I & III mix, D=64nm) their diffraction data is remarkably and consistently different. We have shown that there are significant structural differences between tumour and normal breast tissues with respect to supramolecular collagen architecture; fibril ordering within the tumour tissues is almost completely absent. The data has been supported by histopathological analyses that confirm the preponderance of collagen within all the specimens.

The implications of these findings may be significant as these structural characteristics are new and novel markers of disease progression. Further, we have been able to show that measurable, structural disorder persists at large distances (~cm) from malignant tumours.

Calcifications

We are also interested in assessing the full diagnostic value of calcifications, or microcalcifications, frequently found within breast tissues. These are currently used by radiologists as a first line indicator of disease - certain formation patterns visible on mammograms have been correlated to disease. However, the real nature of these deposits has not yet been determined and, although a wide range of crystalline deposits have been identified, correlations with tumour type, stage or grade have not been studied.

Some tentative but intriguing observations associated with calcifications have been made:

the apparent ability of crystalline phase to act as a marker for tumour type
the possible active role played by calcifications in the progression of disease through stimulation of metalloprotinases
the correlation between lymph node positive and the presence of calcifications
a significantly greater number of lymph nodes are involved with tumours of patients with calcification
the deposition of calcium may be related to tumour cell metastasis?
a correlation between the risk of developing breast cancer and the presence of calcifications and/or trace element concentrations?

We are investigating the deposition of these inorganic materials in relation to the aetiology and development of breast disease.

We believe that the range of phases observed may suggest specific mechanisms of formation i.e. changes in tissue physiology and thus act as a new marker for disease diagnosis.

Synchrotron Imaging

Synchrotron sources of X-rays (such as that at the SRS, Daresbury Laboratory) provide an intense, quasi-parallel beam that is ideal for radiology especially when monochromatic radiation is used. This enables the production of high quality radiographs (i.e. better spatial & contrast resolution) and a significant saving in radiation dose to the patient.

Our work has concerned applying this technology to mammography. A unique feature of our research is our assessment of an imaging system that would simultaneously measure the absorption image (i.e. the radiograph) and the coherent scattering from breast tissues. Thus structural characterisation of collagen and/or the calcifications would be possible in vivo. Although we are some years away from a fully functional system, we have already demonstrated that is possible to produce diffraction images from soft tissue specimens (this should not be confused with the diffraction enhanced imaging techniques currently being developed elsewhere).

EBIG: The Enhanced Breast Imaging Group.