Raman Spectroscopy Reveals That Biochemical Composition of Breast Microcalcifications Correlates with Histopathologic Features

Abstract

Breast microcalcifications (MC) are a common mammographic finding. MC 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 MC are unmet clinical needs. In this study, 473 MC detected on breast biopsy specimens from 56 patients were characterized entirely by Raman mapping, and confirmed by X-ray scattering. MC from malignant samples were generally more homogeneous, more crystalline and characterized by a less substituted crystal lattice compared to 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 MC. The whole Raman signature of each MC was then used to build a classification model that distinguishes MC according to their overall biochemical composition. After validation, MC found in benign and malignant samples were correctly recognized with 93.5% sensitivity and 80.6% specificity. Finally, MC identified in malignant biopsies, but located outside the lesion, reported as well malignant features in 65% of in situ and 98% of invasive cancer cases, respectively, suggesting that the local microenvironment influences MC features. This study confirms that the composition and structural features of MC correlate with breast pathology, and indicates new diagnostic potentialities based on MC assessment.