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

Abstract

BackgroundWomen 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.MethodsMVD 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.ResultsMVD 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.ConclusionsIncreased 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0746-9) contains supplementary material, which is available to authorized users.

Microvessel Density (MVD) in Locally Advanced Breast Cancer

“…This study also reported that MVD as assessed by CD31 or CD34 might be a better prognostic factor than Factor VIII (Uzzan et al, 2004). A more recent study showed that increased MVD of CD31 in whole sections of breast biopsies was significantly associated (OR =1.69, 95% CI=1.17-2.44) with in situ or invasive breast cancer (Felix et al, 2016). However, in our study, MVD as measured by expression of CD31 was not a significant prognostic factor for overall survival in the 92 patients.…”

Application of convolutional neural networks to breast biopsies to delineate tissue correlates of mammographic breast density

“…Details of the BREAST Stamp Project and study eligibility characteristics have been described previously. 25,29,32 Eligible participants were women aged 40–65 years referred for image-guided biopsy who did not have breast implants, had not been diagnosed with breast cancer or received cancer treatments, had not undergone breast surgery within one year and had not received chemoprevention. During the enrollment period, mammography registry data indicated that 1227 patients met these eligibility criteria.…”

“…29 The distribution of the collected breast cancer risk factor information, including the demographic and lifestyle characteristics of the enrolled BREAST Stamp study population, has been previously described. 25,29,32 Details of the analytical population included in this current analysis are outlined in more detail below and described in Table 1. The Institutional Review Boards at the NCI and the University of Vermont approved the protocol for this project for either active consenting or a waiver of consent to enroll participants, link data and perform analytical studies.…”

“…Assessment of breast density was conducted at the University of California, San Francisco on pre-biopsy raw digital mammograms from full-field digital mammography systems. 25,29,32,35,36 Briefly, quantitative global 29 and localized 25 fibroglandular tissue volume (cm 3 ) measures were determined using craniocaudal mammograms of the ipsilateral breast, taken at the time-point prior but nearest to the biopsy date. Percent (%) global fibroglandular volume was estimated using Single X-ray Absorptiometry, which utilized a breast density phantom attached to the compression paddle of the mammography machine.…”

Using deep convolutional neural networks to identify and classify tumor-associated stroma in diagnostic breast biopsies

“…Additionally, by virtue of the deep learning process, it is unclear what components of the stroma may be driving the machine classifier. Additional studies are needed to understand the biology of the stroma surrounding ductal carcinoma in situ, including the role of the vasculature, which we previously showed was increased in ductal carcinoma in situ versus benign biopsies from this study, with the highest microvessel density in invasive carcinoma 45 . Further experiments on larger cohorts of ductal carcinoma in situ with long-term clinical follow-up are needed, to study the potential that stromal features may have prognostic value.…”