Microcalcification crystallography as a potential marker of DCIS recurrence
Sarah Gosling, Emily L. Arnold, Samantha K. Davies, Hannah L. Cross, Ihssane Bouybayoune, Doriana Calabrese, Jayakrupakar Nallala, Sarah E. Pinder, Liping Fu, Esther H. Lips, Lorraine King, Jeffrey R. Marks, Allison Hall, Lars J. Grimm, Thomas R. Lynch, Donna Pinto, Hilary Stobart, E. Shelley Hwang, Jelle Wesseling, Kalotina Geraki, Nicholas Stone, Iain Lyburn, Charlene Greenwood, Keith D. Rogers, Alastair M. Thompson, Serena Nik‐Zainal, Elinor J. Sawyer, Helen Davies, P. Andrew Futreal, Nicholas E. Navin, Jos Jonkers, Jacco van Rheenen, Fariba Behbod, Marjanka K. Schmidt, Lodewyk F.A. Wessels, Daniel Rea, Proteeti Bhattacharjee, Deborah Collyar, Ellen Verschuur, Marja van Oirsouw
Abstract
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.