Biomineralogical signatures of breast microcalcifications

Microcalcifications, primarily biogenic apatite, occur in cancerous and benign breast pathologies and are key mammographic indicators. Outside the clinic, numerous microcalcification compositional metrics (e.g., carbon-ate and metal content) are linked to malignancy, yet microcalcification formation is dependent on microenvi-ronmental conditions, which are notoriously heterogeneous in breast cancer. We interrogate multiscale heterogeneity in 93 calcifications from 21 breast cancer patients using an omics-inspired approach: For each microcalcification, we define a biomineralogical signature combining metrics derived from Raman microscopy and energy-dispersive spectroscopy. We observe that (i) calcifications cluster into physiologically relevant groups reflecting tissue type and local malignancy; (ii) carbonate content exhibits substantial intratumor het-erogeneity; (iii) trace metals including zinc, iron, and aluminum are enhanced in malignant-localized calcifica-tions; and (iv) the lipid-to-protein ratio within calcifications is lower in patients with poor composite outcome, suggesting that there is potential clinical value in expanding research on calcification diagnostic metrics to include mineral-entrapped organic matrix.

Automated summary

Microcalcifications, primarily biogenic apatite, are important indicators in mammography for cancerous and benign breast pathologies. This study investigates the heterogeneity of 93 calcifications from 21 breast cancer patients using an omics-inspired approach, revealing physiological clusters, intratumor heterogeneity in carbonate content, enhanced trace metals in malignant-localized calcifications, and lower lipid-to-protein ratio in patients with poor composite outcome, suggesting potential clinical value in expanding research on calcification diagnostic metrics.