Mammographic microcalcifications and breast cancer tumorigenesis: a radiologic-pathologic analysis

Madiha Naseem, Joshua Murray, John F Hilton, Jason Karamchandani, Derek Muradali, Hala Faragalla, Chanele Polenz, Dolly Han, David C Bell, Christine Brezden-Masley

Microcalcifications (MCs) are tiny deposits of calcium in breast soft tissue. Approximately 30% of early invasive breast cancers have fine, granular MCs detectable on mammography; however, their significance in breast tumorigenesis is controversial. This study had two objectives: (1) to find associations between mammographic MCs and tumor pathology, and (2) to compare the diagnostic value of mammograms and breast biopsies in identifying malignant MCs. A retrospective chart review was performed for 937 women treated for breast cancer during 2000-2012 at St. Michael's Hospital. Demographic information (age and menopausal status), tumor pathology (size, histology, grade, nodal status and lymphovascular invasion), hormonal status (ER and PR), HER-2 over-expression and presence of MCs were collected. Chi-square tests were performed for categorical variables and t-tests were performed for continuous variables. All p-values less than 0.05 were considered statistically significant. A total of 937 patient charts were included. About 38.3% of the patients presented with mammographic MCs on routine mammographic screening. Patients were more likely to have MCs if they were HER-2 positive (52.9%; p < 0.001). There was a significant association between MCs and peri-menopausal status with a mean age of 50 (64%; p = 0.012). Patients with invasive ductal carcinomas (40.9%; p = 0.001) were more likely to present with MCs than were patients with other tumor histologies. Patients with a heterogeneous breast density (p = 0.031) and multifocal breast disease (p = 0.044) were more likely to have MCs on mammograms. There was a positive correlation between MCs and tumor grade (p = 0.057), with grade III tumors presenting with the most MCs (41.3%). A total of 52.2% of MCs were missed on mammograms which were visible on pathology (p < 0.001). This is the largest study suggesting the appearance of MCs on mammograms is strongly associated with HER-2 over-expression, invasive ductal carcinomas, peri-menopausal status, heterogeneous breast density and multifocal disease.