whitlockite and Breast-Neoplasms

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation.

Topics: Breast Neoplasms; Calcinosis; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Crystallography; Female; Humans; Neoplasm Recurrence, Local; Tumor Microenvironment

Breast microcalcifications are a common mammographic finding. Microcalcifications are considered suspicious signs of breast cancer and a breast biopsy is required, however, cancer is diagnosed in only a few patients. Reducing unnecessary biopsies and rapid characterization of breast microcalcifications are unmet clinical needs. In this study, 473 microcalcifications detected on breast biopsy specimens from 56 patients were characterized entirely by Raman mapping and confirmed by X-ray scattering. Microcalcifications from malignant samples were generally more homogeneous, more crystalline, and characterized by a less substituted crystal lattice compared with benign samples. There were significant differences in Raman features corresponding to the phosphate and carbonate bands between the benign and malignant groups. In addition to the heterogeneous composition, the presence of whitlockite specifically emerged as marker of benignity in benign microcalcifications. The whole Raman signature of each microcalcification was then used to build a classification model that distinguishes microcalcifications according to their overall biochemical composition. After validation, microcalcifications found in benign and malignant samples were correctly recognized with 93.5% sensitivity and 80.6% specificity. Finally, microcalcifications identified in malignant biopsies, but located outside the lesion, reported malignant features in 65% of

Topics: Biomarkers; Biopsy; Breast; Breast Carcinoma In Situ; Breast Diseases; Breast Neoplasms; Calcinosis; Calcium Phosphates; Carbonates; Female; Humans; Phosphates; Sensitivity and Specificity; Spectrum Analysis, Raman

Despite the importance of calcifications in early detection of breast cancer, and their suggested role in modulating breast cancer cell behaviour, very little detail is known about their chemical composition or how this relates to pathology. We measured the elemental composition of calcifications contained within histological sections of breast tissue biopsies, and related this to both crystallographic parameters measured previously in the same specimens, and to the histopathology report. The Ca:P ratio is of particular interest since this theoretically has potential as a non-invasive aid to diagnosis; this was found to lie in a narrow range similar to bone, with no significant difference between benign and malignant. The Mg:Ca ratio is also of interest due to the observed association of magnesium whitlockite with malignancy. The initially surprising inverse correlation found between whitlockite fraction and magnesium concentration can be explained by the location of the magnesium in calcified tissue. Sodium was also measured, and we discovered a substantial and significant difference in Na:Ca ratio in the apatite phase between benign and malignant specimens. This has potential for revealing malignant changes in the vicinity of a core needle biopsy.

Topics: Breast; Breast Neoplasms; Calcinosis; Calcium; Calcium Phosphates; Electron Probe Microanalysis; Female; Humans; Magnesium; Phosphorus; Sodium