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Breast calcification chemistry as a biomarker for progression of in-situ breast cancer

DOI: 10.1016/j.bonr.2021.100787 DOI Help

Authors: Sarah Gosling (Cranfield University) , Doriana Calabrese (University of Exeter) , Emily Arnold (Cranfield University) , Jayakrupakar Nallala (University of Exeter) , Charlene Greenwood (Keele University) , Nicholas Stone (University of Exeter) , Keith Rogers (Cranfield University)
Co-authored by industrial partner: No

Type: Conference Paper
Conference: 48th European Calcified Tissue Society Congress ECTS 2021
Peer Reviewed: No

State: Published (Approved)
Published: May 2021

Open Access Open Access

Abstract: Background/Introduction: Breast microcalcifications are deposits of calcium oxalate, found mostly in benign tissue, or calcium phosphate in the form of hydroxyapatite, found in benign and malignant tissue. Differences in the crystallographic properties and chemical make-up of hydroxyapatite breast microcalcifications have previously been noted in differing breast pathologies. Purpose: Ductal carcinoma in-situ (DCIS) is a precancerous breast lesion, which has the potential to form invasive breast cancer. Currently there are no definitive markers to determine DCIS invasiveness, therefore this work aims to elucidate differences in the calcification chemistry between invasive and non-invasive cases of DCIS, ultimately developing a novel biomarker for DCIS progression. Methods: 75 formalin fixed paraffin embedded archive breast tissue samples were used subject to NHS REC approval (ref. 18/LO/0945). X-ray diffraction was carried out at 12keV on beamline i18 at Diamond Light Source, UK to determine crystallographic properties of 279 breast calcifications. SEM-EDS experiments were carried out on a Hitachi SU3500 at 11kV under low vacuum. Results: Significant differences (P < 0.05) were observed in the proportion of magnesium whitlockite found as a secondary phase in breast calcifications from invasive (3.51 %) and non-invasive (2.82 %) DCIS samples. Additionally, crystallographic features of hydroxyapatite, the bulk of calcifications in both cases, were found to differ between the two groups. The d-spacing between crystallographic planes, was significantly (P < 0.001) larger in invasive compared to non-invasive DCIS cases. Finally, the calcium to phosphate ratio measured using EDS was significantly lower (P < 0.001) in invasive samples (1.60) compared to non-invasive samples (1.67), which more closely reflected stoichiometric hydroxyapatite. Conclusion(s): Differences in calcification chemistry and crystallographic structure between invasive and non-invasive DCIS cases have been demonstrated in this study. Therefore, calcification chemistry is a key candidate for novel DCIS progression biomarkers and could ultimately lower treatment expenditure and improve patient quality of life by reducing overtreatment.

Diamond Keywords: Breast Cancer

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I18-Microfocus Spectroscopy

Discipline Tags:

Biochemistry Cancer Chemistry Health & Wellbeing Life Sciences & Biotech Non-Communicable Diseases

Technical Tags:

Diffraction