Abstract
Calcifications are not only one of the most important early diagnostic markers of breast cancer, but are also increasingly believed to aggravate the proliferation of cancer cells and invasion of surrounding tissue. Moreover, this influence appears to vary with calcification composition. Despite this, remarkably little is known about the composition and crystal structure of the most common type of breast calcifications, and how this differs between benign and malignant lesions. We sought to determine how the phase composition and crystallographic parameters within calcifications varies with pathology, using synchrotron X-ray diffraction. This is the first time crystallite size and lattice parameters have been measured in breast calcifications, and we found that these both parallel closely the changes in these parameters with age observed in fetal bone. We also discovered that these calcifications contain a small proportion of magnesium whitlockite, and that this proportion increases from benign to in situ to invasive cancer. When combined with other recent evidence on the effect of magnesium on hydroxyapatite precipitation, this suggests a mechanism explaining observations that carbonate levels within breast calcifications are lower in malignant specimens.
Highlights
Calcifications associated with breast cancer consist predominantly of hydroxyapatite, and there is evidence that nanoscale properties of hydroxyapatite may have an important role in regulating breast cancer cell behavior.[6]
No calcium oxalate was found in 236 calcifications from 110 patients in an FTIR study of samples taken from the same archive.[16]
The specimen numbers in this pilot study were small, the absence of calcium oxalate in these results suggests a proportion towards the lower end of this range
Summary
Despite the central role of calcifications in the early detection of breast cancer, their pathophysiology and chemistry remain poorly understood.[1,2,3] This is important for two reasons: First, there is evidence that calcifications in breast cancer are not passive products of the disease process, but may have an active role in mitogenesis, upregulation of gene expression and enhanced migration of tumor cells.[1,4,5] In particular, calcifications associated with breast cancer consist predominantly of hydroxyapatite, and there is evidence that nanoscale properties of hydroxyapatite may have an important role in regulating breast cancer cell behavior.[6]. Calcification chemistry has potential for use in diagnosis, either as an objective adjunct to conventional histopathology, or by noninvasive probing, e.g., using Raman spectroscopy.[7,8,9] Given that mammography screening only has a 20% positive predictive value,[10] and that in breast pathology ‘Many gradations of normal, precancerous, and cancerous conditions are often indistinguishable, making clear-cut diagnosis very difficult and often a cause for intense debate’,11 accurate, rapid, and objective aids to diagnosis clearly have a role.[12]
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