Biomineralogical signatures of breast microcalcifications

Abstract

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., carbonate and metal content) are linked to malignancy, yet microcalcification formation is dependent on microenvironmental 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 heterogeneity; (iii) trace metals including zinc, iron, and aluminum are enhanced in malignant-localized calcifications; 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.

Multicellular spheroids containing synthetic mineral particles: an advanced 3D tumor model system to investigate breast precancer malignancy potential according to the mineral type

“…1–3 These pathological biominerals are highly diverse, presenting various compositions, crystal phases, crystallinities, morphologies, and particle sizes. 4–7 Since biominerals can be used for disease diagnosis, prognosis, and biomedical applications, it is crucial to better understand their interactions with cells and tissues, considering the wide variety of physiologically relevant mineral types. 8,9 Breast precancer is a well-documented example of a pathological condition tightly connected to mineral formation.…”

Calcium-based biomaterials: Unveiling features and expanding applications in osteosarcoma treatment

“…As a consequence of disrupt calcium homeostasis, calcium deposition causes calcification. In the clinic, spontaneous calcification has been detected in a wide range of cancers, and has been shown to be a benign prognostic factor [ 98 , 99 ]. In tumour biology, calcification is always associated with the local haemorrhage caused by damaged blood vessels.…”

The interplay between crystallinity and the levels of Zn and carbonate in synthetic microcalcifications directs thyroid cell malignancy

“…12 For instance, carbonate may substitute for either phosphate or hydroxyl ions within the lattice while mono-and divalent cations can substitute for calcium. 8,13 In breast MCs, there is a correlation between the crystal properties and tissue malignancy: the more malignant the tissue, the higher the crystallinity 13 and the fractions of Na, Mg, and Zn found in the MCs 10,14,15 and the lower the carbonate fraction. 10 Motivated by the connection between MC composition and breast tissue malignancy, several previous studies have focused on characterizing the composition of thyroid MCs.…”