Abstract 2768: Relationships between mammographic density, microvessel density, and breast biopsy diagnosis
Authors: Felix Ashley S. , Lenz Petra , Pfeiffer Ruth M. , Hewitt Stephen M. , Morris Jennifer , Patel Deesha , Geller Berta , Vacek Pamela M. , Weaver Donald L. , Chicoine Rachael E. , Shepherd John , Mahmoudzadeh Amir P. , Wang Jeff , Fan Bo , Herschorn Sally , Johnson Jason , Brinton Louise A. , Sherman Mark E. , Gierach Gretchen L. 
Published: August 2015

Abstract
Introduction: Mammographic density (MD) is a strong breast cancer risk factor; however, the majority of women with high MD have neither a prevalent tumor nor will they develop one in immediate follow-up. Magnetic resonance imaging (MRI) studies suggest that background parenchymal enhancement, an indicator of vascularity, is another strong breast cancer risk predictor. However, it is uncertain how correlated microvessel density (MVD), a histological marker of vascularity, is with MD and if it adds information for disease detection. We therefore investigated relationships between MVD, area and volume measures of MD, and biopsy diagnosis among 218 women referred for image-guided vacuum-assisted breast biopsies.
Methods: MVD was determined by counting CD31 (endothelial marker) positive vessels in whole sections of breast biopsies in three areas containing five 40X high power fields. Average MVD per area was calculated and then transformed based on a Box-Cox analysis to approximate a normal distribution. MD volume was quantified using single X-ray absorptiometry (SXA) in digital mammograms and MD area was quantified on the same image using thresholding methods. We used linear regression to evaluate associations between MVD (as the outcome) and MD measures (area and volume) adjusted for age and body mass index (BMI) in the overall population and stratified by biopsy diagnosis: cases (in situ or invasive carcinoma, n = 44) vs. non-cases (non-proliferative or proliferative benign breast disease, n = 174). Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between MVD and biopsy diagnosis (cases vs. non-cases) in models adjusted for age, BMI, and MD measures.
Results: MVD was inversely associated with absolute dense area and absolute dense volume in the overall sample (area p = 0.01, volume p = 0.11) and among non-cases (area p = 0.009, volume p = 0.007). In age-, BMI-, and dense area- or dense volume- adjusted logistic regression models, MVD was significantly associated with risk of in situ/invasive disease independent of absolute dense area (OR = 1.16, 95% CI = 1.04, 1.28) and independent of absolute dense volume (OR = 1.16, 95% CI = 1.05-1.29).
Conclusion: Our histopathologic analysis suggests that tissue vascularity, as reflected by MVD, may predict breast cancer risk independently of MD, thus providing theoretical support for the potential utility in breast cancer detection of imaging methods that reflect vascularity, such as contrast-enhanced MRI.
Citation Format: Ashley S. Felix, Petra Lenz, Ruth M. Pfeiffer, Stephen M. Hewitt, Jennifer Morris, Deesha Patel, Berta Geller, Pamela M. Vacek, Donald L. Weaver, Rachael E. Chicoine, John Shepherd, Amir P. Mahmoudzadeh, Jeff Wang, Bo Fan, Sally Herschorn, Jason Johnson, Louise A. Brinton, Mark E. Sherman, Gretchen L. Gierach. Relationships between mammographic density, microvessel density, and breast biopsy diagnosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2768. doi:10.1158/1538-7445.AM2015-2768