title: New relationships between breast microcalcifications and cancer.
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.
authors.affiliation: Biophotonics Research Unit, Gloucestershire Hospitals NHS Foundation Trust, Great Western Road, Gloucester, GL1 3NN,UK.
authors.forename: R
authors.initials: R
authors.lastname: Baker
authors.forename: K D
authors.initials: KD
authors.lastname: Rogers
authors.forename: N
authors.initials: N
authors.lastname: Shepherd
authors.forename: N
authors.initials: N
authors.lastname: Stone
mesh_terms: D001941:Breast Diseases / Q000473:pathology*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology*; D002114:Calcinosis / Q000473:pathology*; D002254:Carbonates / Q000032:analysis*; D002277:Carcinoma / Q000473:pathology; D002278:Carcinoma in Situ / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000473:pathology; D005260:Female; D006801:Humans
chemical_list: D002254:Carbonates