PROJECT AIMS

Within the UK there are >55000 new cases of breast cancer diagnosed every year (world-wide >1.7 million) and the economic cost of breast cancer to the UK is >£1.5bn per annum. Early and accurate diagnoses are critical for the most effective treatments and reduced costs. Current diagnostic inadequacies are characterised by (i) an >80% false positive rate for mammography, (ii) significant overtreatment of some breast cancers, and, (iii) equivocal histopathology leading to uncertain prognoses.

This work will generate a new understanding of the physicochemistry of involved tissues and, as a result, will identify potential new biomarkers and diagnostic methods. We are adopting a new, multidisciplinary approach to disease diagnosis, and combining the expertise of senior clinicians with material scientists to study tissue physicochemistry. We are also exploiting a distinct, retrospective approach to sampling that is enabling access to unprecedented patient numbers. Successful outcomes from this work will have significant impacts for understanding disease and development of accurate breast cancer diagnostics.

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Calcifications within breast tissues are used as a primary marker of malignancy although the precipitation mechanism of biologically derived calcifications remains a matter of considerable debate. In contrast, the capacity of apatites to incorporate 'foreign', environmental ions at the time of precipitation is incontrovertible. Thus chemical features of tissue physiology at the point of formation become immortalised within calcifications. Precipitation of calcific phases in vivo is triggered by slight modifications to tissue chemistry and this, in the case of breast tissue, occurs at the very onset of the cancer.

Image Above: Histological staining (H&E), scanning electron microscopy (SEM), elemental analysis (EDS) and x-ray diffraction (XRD) images of a breast microcalcification (Gosling et al, 2020). 

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Our primary hypothesis then is that apatite calcification physicochemical characteristics may be employed as novel biomarkers of cancer. The primary aim of this project is to determine and understand the underpinning physicochemical characteristics of breast tissue calcifications to enable future development of in vivo, accurate diagnostic probes. The project is (a) identifying archived specimen populations representing a wide range of tumour subtypes for material analyses, (b) exploiting cutting edge physical methods of high resolution calcification characterisation and, (c) relating calcification physicochemistry to clinical diagnosis and prognosis.

Successful outcomes from this work will have significant impacts for understanding disease and development of accurate breast cancer diagnostics.

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Image below: Mean carbonate content in calcifications, calculated using mid-Fouries transform infrared (FTIR) spectroscopy, from invasive, in-situ and benign breast tissue groups studied. Error bars show the standard deviation of the values measured (Baker et al, 2010). 

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