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There has been considerable recent interest in the genetic, biological and epidemiological basis of mammographic density (MD), and the search for causative links between MD and breast cancer (BC) risk. This report will critically review the current literature on MD and summarize the current evidence for its association with BC. Keywords 'mammographic dens*', 'dense mammary tissue' or 'percent dens*' were used to search the existing literature in English on PubMed and Medline. All reports were critically analyzed. The data were assigned to one of the following aspects of MD: general association with BC, its relationship with the breast hormonal milieu, the cellular basis of MD, the generic variations of MD, and its significance in the clinical setting. MD adjusted for age, and BMI is associated with increased risk of BC diagnosis, advanced tumour stage at diagnosis and increased risk of both local recurrence and second primary cancers. The MD measures that predict BC risk have high heritability, and to date several genetic markers associated with BC risk have been found to also be associated with these MD risk predictors. Change in MD could be a predictor of the extent of chemoprevention with tamoxifen. Although the biological and genetic pathways that determine and perhaps modulate MD remain largely unresolved, significant inroads are being made into the understanding of MD, which may lead to benefits in clinical screening, assessment and treatment strategies. This review provides a timely update on the current understanding of MD's association with BC risk. [ABSTRACT FROM AUTHOR]

Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal ( p = 0.0002) and lower adipose ( p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area ( p = 0.4) or count ( p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer. [ABSTRACT FROM AUTHOR]