No abstract

Background:Breast microcalcifications are key diagnostically significant radiological features for localisation of malignancy. This study explores the hypothesis that breast calcification composition is directly related to the local tissue pathological state.Methods:A total of 236 human breast calcifications from 110 patients were analysed by mid-Fouries transform infrared (FTIR) spectroscopy from three different pathology types (112 invasive carcinoma (IC), 64 in-situ carcinomas and 60 benign). The biochemical composition and the incorporation of carbonate into the hydroxyapatite lattice of the microcalcifications were studied by infrared microspectroscopy. This allowed the spectrally identified composition to be directly correlated with the histopathology grading of the surrounding tissue.Results:The carbonate content of breast microcalcifications was shown to significantly decrease when progressing from benign to malignant disease. In this study, we report significant correlations (P<0.001) between microcalcification chemical composition (carbonate content and protein matrix : mineral ratios) and distinct pathology grades (benign, in-situ carcinoma and ICs). Furthermore, a significant correlation (P<0.001) was observed between carbonate concentrations and carcinoma in-situ sub-grades. Using the two measures of pathology-specific calcification composition (carbonate content and protein matrix : mineral ratios) as the inputs to a two-metric discriminant model sensitivities of 79, 84 and 90% and specificities of 98, 82 and 96% were achieved for benign, ductal carcinoma in situ and invasive malignancies, respectively.Conclusions:We present the first demonstration of a direct link between the chemical nature of microcalcifications and the grade of the pathological breast disease. This suggests that microcalcifications have a significant association with cancer progression, and could be used for future objective analytical classification of breast pathology. A simple two-metric model has been demonstrated, more complex spectral analysis may yeild greater discrimination performance. Furthermore there appears to be a sequential progression of calcification composition.

No abstract

Breast calcifications are often the only mammographic features indicating the presence of a cancerous lesion. Calcium oxalate (type I) may be found in and around benign lesions, however calcium hydroxyapatite (type II) is usually found within proliferative lesions, which can include both benign and malignant pathologies. However, the composition of type II calcifications has been demonstrated to vary between benign and malignant proliferative lesions, and could be an indicator for the possible disease state. Raman spectroscopy has previously been demonstrated as a powerful tool for non-destructive analysis of tissues, utilising laser light to probe chemical composition. Raman spectroscopy is traditionally a surface technique. However, we have recently developed methods that permit its application for obtaining sample composition to clinically relevant depths of many mm. We report the first demonstration of spatially offset Raman spectroscopy (SORS) for potential in vivo breast analysis. This study evaluates the possibility of utilising SORS for measuring calcification composition through varying thicknesses of tissues (2 to 10 mm), which is about one to two orders of magnitude deeper than has been possible with conventional Raman approaches. SORS can be used to distinguish non-invasively between calcification types I and II (and carbonate substitution of phosphate in calcium hydroxyapatite) within tissue of up to 10 mm deep. This result secures the first step in taking this technique forward for clinical applications seeking to use Raman spectroscopy as an adjunct to mammography for early diagnosis of breast cancer, by utilising both soft tissue and calcification signals. Non-invasive elucidation of calcification composition, and hence type, associated with benign or malignant lesions, could eliminate the requirement for biopsy in many patients.