Relationships between mammographic density, tissue microvessel density, and breast biopsy diagnosis

Ashley S. Felix, Petra Lenz, Ruth M. Pfeiffer, Stephen M. Hewitt, Jennifer Morris, Deesha A. Patel, Berta Geller, Pamela M. Vacek, Donald L. Weaver, Rachael E. Chicoine, John Shepherd, Amir Pasha Mahmoudzadeh, Jeff Wang, Bo Fan, Serghei Malkov, Sally D. Herschorn, Jason M. Johnson, Renata L. Cora, Louise A. Brinton, Mark E. Sherman, Gretchen L. Gierach

Women with high levels of mammographic density (MD) have a four- to six-fold increased risk of developing breast cancer; however, most neither have a prevalent tumor nor will they develop one. Magnetic resonance imaging (MRI) studies suggest that background parenchymal enhancement, an indicator of vascularity, is related to increased breast cancer risk. Correlations of microvessel density (MVD) in tissue, MD and biopsy diagnosis have not been defined, and we investigated these relationships among 218 women referred for biopsy. MVD was determined by counting CD31-positive vessels in whole sections of breast biopsies in three representative areas; average MVD was transformed to approximate normality. Using digital mammograms, we quantified MD volume with single X-ray absorptiometry. We used linear regression to evaluate associations between MVD and MD adjusted for age and body mass index (BMI) overall, and stratified by biopsy diagnosis: cases (in situ or invasive cancer, n = 44) versus non-cases (non-proliferative or proliferative benign breast disease, n = 174). Logistic regression adjusted for age, BMI, and MD was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between MVD and biopsy diagnosis. We also assessed whether the MVD-breast cancer association varied by MD. MVD and MD were not consistently associated. Higher MVD was significantly associated with higher odds of in situ/invasive disease (ORAdjusted = 1.69, 95 % CI = 1.17-2.44). MVD-breast cancer associations were strongest among women with greater non-dense volume. Increased MVD in tissues is associated with breast cancer, independently of MD, consistent with MRI findings suggestive of its possible value as a radiological cancer biomarker.