Benign Arterial Calcification on Screening Mammogram: A Marker for Coronary Artery Disease?

BACKGROUND: Studies have shown several risk factors for coronary artery disease (CAD), such as diabetes and hypertension, are associated with benign arterial calcifications (BACs) seen on screening mammograms. However, there are few studies examining the association of BACs with women who are diagnosed with CAD. The purpose of our study was to determine whether there is an association between BACs present on routine screening digital mammograms and the presence of CAD as documented on cardiac catheterization. METHODS: A retrospective chart review was performed on women aged ≥40 years who had undergone a digital screening mammogram within two years of also having a cardiac catheterization from 1999 to 2010. Mammograms were reviewed for the presence of BACs. Cardiac catheterizations were reviewed for the presence of CAD. Patients with BACs were compared with those without BACs by chi-squared or Wilcoxon rank sum tests. RESULTS: The final study cohort consisted of 198 patients with 101 patients having clinically significant cardiac vessel disease. Most patients (67.2%) did not have diabetes, while the majority was hypertensive (83.3%) and had hypercholesterolemia (80.8%). On multivariate analysis, history of smoking (p=0.003), hypercholesterolemia (p≤0.0001), and BACs (p=0.005) were significant predictors of CAD. In a second model, CAD on cardiac catheterization was a significant predictor of BACs found on mammography while a history of smoking was a negative predictor of BACs. CONCLUSIONS: BACs present on digital screening mammography, history of smoking and hypercholesterolemia were all significant predictors of CAD. Routine screening digital mammography could potentially assist in stratification of patients in consideration of CAD.

Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer.

INTRODUCTION: Aberrant methylation of CpG islands is a hallmark of cancer and occurs at an early stage in breast tumorigenesis. However, its impact on tumor development is not fully determined, and its potential as a diagnostic biomarker remains to be validated. Methylation profiling of invasive breast carcinoma has been largely explored. Conversely, very little and sparse information is available on early-stage breast cancer. To gain insight into the epigenetic switches that may promote and/or contribute to the initial neoplastic events during breast carcinogenesis, we have analyzed the DNA methylation profile of ductal carcinoma in situ, a premalignant breast lesion with a great potential to progress toward invasive carcinoma. METHODS: We have utilized a comprehensive and sensitive array-based DNA mapping technique, the methylated-CpG island recovery assay, to profile the DNA methylation pattern in ductal carcinoma in situ. Differential methylation of CpG islands was compared genome-wide in tumor DNA versus normal DNA utilizing a statistical linear model in the LIMMA software package. RESULTS: Using this approach, we have identified 108 significant CpG islands that undergo aberrant DNA methylation in ductal carcinoma in situ and stage I breast tumors, with methylation frequencies greater than or comparable with those of more advanced invasive carcinoma (50% to 93%). A substantial fraction of these hypermethylated CpG islands (32% of the annotated CpG islands) is associated with several homeobox genes, such as the TLX1, HOXB13, and HNF1B genes. Fifty-three percent of the genes hypermethylated in early-stage breast cancer overlap with known Polycomb targets and include homeobox genes and other developmental transcription factors. CONCLUSIONS: We have identified a series of new potential methylation biomarkers that may help elucidate the underlying mechanisms of breast tumorigenesis. More specifically, our results are suggestive of a critical role of homeobox gene methylation in the insurgence and/or progression of breast cancer.